bluuebunny/crossref_metadata_2025 huggingface dataset:
β-Hydroxybutyrate Alleviates Atherosclerotic Calcification by Inhibiting Endoplasmic Reticulum Stress-Mediated Apoptosis via AMPK/Nrf2 Pathway
Authors: Chen Yu , You Yiran , Wang Xin , Jin Yufeng , Zeng Yupeng , Pan Zhijun , Li Dan , Ling Wenhua
Published: December 2024

Background: Atherosclerotic calcification (AC) is a common feature of atherosclerotic cardiovascular disease. β-Hydroxybutyrate (BHB) has been identified as a molecule that influences cardiovascular disease. However, whether BHB can influence AC is still unknown. Methods and Results: In this study, ApoE−/− mice, fed a Western diet, were used to examine the effects of BHB on AC. Rat vascular smooth muscle cells (VSMCs) were used to verify the impacts of BHB on AC and to explore the underlying mechanisms. The results show that Western diet-challenged ApoE−/− mice, supplemented with BHB for 24 weeks, exhibited reduced calcified areas, calcium content, and alkaline phosphatase (ALP) activity in the aortas, as well as ameliorated severity of AC. Furthermore, BHB downregulated the expression of glucose-regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP), thereby reducing endoplasmic reticulum stress (ERS) and ERS-mediated apoptosis in the aortas of the mice. Consistently, in vitro studies showed that BHB reduced ALP activity and calcium content in VSMCs, and inhibited VSMC calcification. Additionally, BHB suppressed ERS-mediated apoptosis in VSMCs. Conclusions: In summary, the present results demonstrate that BHB can alleviate atherosclerotic calcification by inhibiting ERS-mediated apoptosis. Therefore, BHB may serve as a viable therapeutic agent for AC.
Rice Bran Consumption Improves Lipid Profiles: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Park Soo-yeon , Kim Yehyeon , Park Min , Kim Ji
Published: December 2024

Background: Dyslipidemia, a leading risk factor for cardiovascular diseases (CVDs), significantly contributes to global morbidity and mortality. Rice bran, rich in bioactive compounds such as γ-oryzanol and tocotrienols, has demonstrated promising lipid-modulating effects. Objective: This meta-analysis aimed to evaluate the effects of rice bran on lipid profiles, including triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C), and identify factors influencing its efficacy across different populations and intervention conditions. Methods: A systematic search of PubMed, Web of Science, and Scopus was conducted to identify randomized controlled trials (RCTs) published up to November 2024. Effect sizes were calculated as mean differences with 95% confidence intervals (CIs). Subgroup analyses were performed based on intervention form, dosage, duration, region, and participant characteristics. Heterogeneity was estimated by the I2 statistic, and sensitivity analyses were conducted to assess the robustness of the findings. Results: Eleven RCTs involving 572 participants met the inclusion criteria. Pooled results showed that rice bran consumption significantly reduced TG (−15.13 mg/dL; 95% CI: −29.56, −0.71), TC (−11.80 mg/dL; 95% CI: −19.35, −4.25), and LDL-C (−15.11 mg/dL; 95% CI: −24.56, −5.66) with moderate heterogeneity (I2 = 38.1–63.0%). No significant changes were observed for HDL-C. Subgroup analyses showed that rice bran oil had greater effects on TC and LDL-C than whole rice bran. High-dose interventions (≥30 g/mL) and longer durations (>4 weeks) yielded stronger effects. Asian populations demonstrated greater reductions compared to Western populations. Conclusion: Rice bran, especially in the form of rice bran oil, significantly improves lipid profiles, supporting its role as a functional food for CVD prevention. Future research should focus on long-term studies with diverse populations to confirm its efficacy and explore underlying mechanisms.
A Personalized Approach to Vitamin D Supplementation in Cardiovascular Health Beyond the Bone: An Expert Consensus by the Italian National Institute for Cardiovascular Research
Authors: Mattioli Anna Vittoria , Coppi Francesca , Severino Paolo , Penna Claudia , Pagliaro Pasquale , Dei Cas Alessandra , Bucciarelli Valentina , Madonna Rosalinda , Tarperi Cantor , Schena Federico , Cetrullo Silvia , Angelone Tommaso , Rocca Carmine , Parenti Astrid , Palazzuoli Alberto , Margonato Alberto , Paolillo Stefania , Perrone Filardi Pasquale , Barillà Francesco , Lombardi Carlo , Pinti Marcello , Molinari Claudio , Cevese Antonio , Novo Giuseppina , Pizzi Carmine , Porto Italo , Poggesi Corrado , Gallina Sabina , Ambrosio Giuseppe , Fedele Francesco ,   on behalf of the Italian National Institute for Cardiovascular Research (INRC)
Published: December 2024

Vitamin D is increasingly recognized for its role in cardiovascular health beyond its well-established effects on bone metabolism. This review synthesizes findings from observational studies, interventional trials, and meta-analyses to clarify the mechanisms through which vitamin D impacts cardiovascular health, including its influence on vascular function, inflammation, and metabolic pathways. Additionally, this review emphasizes the importance of a personalized approach to vitamin D supplementation, integrating individual cardiovascular risk profiles, baseline vitamin D levels, and comorbid conditions, such as hypertension and diabetes. While current evidence supports the association between low vitamin D levels and increased cardiovascular mortality, this work contributes novel insights by proposing tailored strategies for supplementation, particularly for high-risk subgroups. Practical recommendations for implementing these strategies in clinical practice are also discussed, providing a framework for optimizing cardiovascular outcomes through individualized vitamin D management.
Human Milk Oligosaccharides: Decoding Their Structural Variability, Health Benefits, and the Evolution of Infant Nutrition
Authors: Duman Hatice , Bechelany Mikhael , Karav Sercan
Published: December 2024

Human milk oligosaccharides (HMOs), the third most abundant solid component in human milk, vary significantly among women due to factors such as secretor status, race, geography, season, maternal nutrition and weight, gestational age, and delivery method. In recent studies, HMOs have been shown to have a variety of functional roles in the development of infants. Because HMOs are not digested by infants, they act as metabolic substrates for certain bacteria, helping to establish the infant’s gut microbiota. By encouraging the growth of advantageous intestinal bacteria, these sugars function as prebiotics and produce short-chain fatty acids (SCFAs), which are essential for gut health. HMOs can also specifically reduce harmful microbes and viruses binding to the gut epithelium, preventing illness. HMO addition to infant formula is safe and promotes healthy development, infection prevention, and microbiota. Current infant formulas frequently contain oligosaccharides (OSs) that differ structurally from those found in human milk, making it unlikely that they would reproduce the unique effects of HMOs. However, there is a growing trend in producing OSs resembling HMOs, but limited data make it unclear whether HMOs offer additional therapeutic benefits compared to non-human OSs. Better knowledge of how the human mammary gland synthesizes HMOs could direct the development of technologies that yield a broad variety of complex HMOs with OS compositions that closely mimic human milk. This review explores HMOs’ complex nature and vital role in infant health, examining maternal variation in HMO composition and its contributing factors. It highlights recent technological advances enabling large-scale studies on HMO composition and its effects on infant health. Furthermore, HMOs’ multifunctional roles in biological processes such as infection prevention, brain development, and gut microbiota and immune response regulation are investigated. The structural distinctions between HMOs and other mammalian OSs in infant formulas are discussed, with a focus on the trend toward producing more precise replicas of HMOs found in human milk.
Dietary Habits of Pregnant Women in Spain: The Role of Nutrition Education in Midwife Consultations
Authors: Olloqui-Mundet M. Josefa , Palma-Morales Marta , Cantarell-González M. Carmen , Cavia M. Mar , Alonso-Torre Sara R. , Ocón-Hernández Olga , Rodríguez-Pérez Celia , Carrillo Celia
Published: December 2024

Background & Objectives: Correct nutrition during pregnancy is key to guaranteeing success at this stage of a woman’s life, and nutritional education is the fundamental tool for achieving this. Studies carried out in different countries indicate that pregnant women do not comply with dietary and nutritional recommendations. Given the lack of evidence available in Spain and the importance of this knowledge to be able to assess the need for nutritional intervention in this group, the aim of this study focused on the current status of the issue in Spain: the quality of the diet of Spanish pregnant women and its conditioning factors. Methods: Two representative regions of the country were selected, one located in the north of Spain (Burgos) and the other in the south (Granada), and a descriptive, cross-sectional observational study (sample size: 771) was carried out using a questionnaire administered at the University Hospital of Burgos and the Hospital Clínico San Cecilio in Granada, which had previously been subjected to a process of evaluation by expert judgement. Results: Pregnant women presented an adequate diet quality (8.0 ± 2.0), according to the questionnaire used, despite their poor knowledge of food and nutrition (4.9 ± 1.6 out of 10). However, deficiencies were detected in the consumption of very interesting food groups from a nutritional point of view, such as legumes, nuts and fish (just 29.4%, 37.6% and 24.8% of the pregnant women met the recommendations, respectively) and insufficient physical exercise. The eating habits of pregnant women depend on their age, their country of origin, their level of education, their pre-pregnancy BMI, the knowledge acquired during pregnancy and the degree to which they put into practice the advice received from their midwife. Most pregnant women do not change their habits during pregnancy, although there are positive trends in this respect. Conclusion: The quality of the diet of the Spanish pregnant women surveyed, and their level of physical activity, could be improved by enhancing the nutritional education they receive during this stage of life. The role of the dietician in this respect, as part of multidisciplinary teams, should be the basis for future research.
The Unripe Carob Extract (Ceratonia siliqua L.) as a Potential Therapeutic Strategy to Fight Oxaliplatin-Induced Neuropathy
Authors: Micheli Laura , Muraglia Marilena , Corbo Filomena , Venturi Daniel , Clodoveo Maria Lisa , Tardugno Roberta , Santoro Valentina , Piccinelli Anna Lisa , Di Cesare Mannelli Lorenzo , Nobili Stefania , Ghelardini Carla
Published: December 2024

Background: Oxaliplatin-induced neuropathy (OIN) is a severe painful condition that strongly affects the patient’s quality of life and cannot be counteracted by the available drugs or adjuvants. Thus, several efforts are devoted to discovering substances that can revert or reduce OIN, including natural compounds. The carob tree, Ceratonia siliqua L., possesses several beneficial properties. However, its antalgic properties have not been substantially investigated and only a few investigations have been conducted on the unripe carob (up-CS) pods. Thus, the aims of this study were to evaluate for the first time the unripe variety of Apulian carob, chemically characterized and profiled as antioxidant potential of polyphenolic compounds as well as to investigate the ability of up-CS to reduce the neurotoxicity in a mouse model of oxaliplatin-induced neuropathic pain. Methods: By UHPLC-HRMS/MS analyses, 50 phenolic compounds, belonging mainly to n-galloylated glucoses and flavonoids were detected. Results: In a mouse model of oxaliplatin-induced neurotoxicity (2.4 mg/kg, 10 injections over two weeks), acute per os treatment with up-CS provoked a dose-dependent pain-relieving effect that completely counteracted oxaliplatin hypersensitivity at the dose of 200 mg/kg. Repeated oral administration of up-CS (100 mg/kg), concomitantly with oxaliplatin injection, exerted a protective effect against the development of thermal and mechanical allodynia. In addition, up-CS exerted a neuroprotective role against oxaliplatin-induced astrocytes activation in the spinal cord measured as GFAP-fluorescence intensity. Conclusions: Overall, our study contributes to the knowledge on up-CS properties by highlighting its protective activity in the painful condition related to the administration of oxaliplatin.
Metabolic Dysfunction-Associated Steatotic Liver Disease and the Risk of Chronic Periodontitis: A Nationwide Cohort Study
Authors: Shine Bo-Kyung , Son Minkook , Moon Sang Yi , Han Seong-Ho
Published: December 2024

Background: Chronic periodontitis (CP) and metabolic dysfunction-associated steatotic liver disease (MASLD) have emerged as interconnected conditions with shared mechanisms, such as systemic inflammation and metabolic dysregulation. However, the risk of CP in the newly classified subgroups of steatotic liver disease (SLD), including MASLD and metabolic alcohol-associated liver disease (MetALD), has not been extensively studied. This study investigated the association between SLD subtypes and the incidence of CP in a nationwide cohort. Methods: This retrospective cohort study used data from the Korean National Health Insurance Service database. The study included 115,619 participants aged 40 and older who underwent health screenings between 2009 and 2010. The participants were classified into four groups: normal without risk factors, normal with risk factors, MASLD, and MetALD. The primary outcome was the incidence of CP as defined by ICD-10 codes and dental treatment records. Hazard ratios (HRs) were calculated using the Cox proportional hazards model and adjusted for demographic, clinical, and lifestyle factors. Results: Over a mean follow-up of 7.4 years, individuals with MASLD and MetALD had significantly higher risks of developing CP compared with the normal group without risk factors (MASLD: adjusted HR 1.14, 95% confidence interval (CI): 1.11–1.17; MetALD: adjusted HR 1.21, 95% CI: 1.15–1.27). The risk was more pronounced for severe CP, particularly for those with MetALD (adjusted HR 1.29, 95% CI: 1.22–1.36). Subgroup and sensitivity analyses confirmed these findings across the various definitions of hepatic steatosis and metabolic risk factors. Conclusions: This study reveals that individuals with MASLD and MetALD are at an elevated risk of developing CP, highlighting the need for integrated care strategies that address both periodontal health and metabolic liver conditions. These findings underscore the importance of periodontal health management in reducing the risk of CP among SLD populations.
Preconceptional and Periconceptional Folic Acid Supplementation in the Visegrad Group Countries for the Prevention of Neural Tube Defects
Authors: Rísová Vanda , Saade Rami , Jakuš Vladimír , Gajdošová Lívia , Varga Ivan , Záhumenský Jozef
Published: December 2024

Neural tube defects (NTDs) are malformations of the central nervous system that represent the second most common cause of congenital morbidity and mortality, following cardiovascular abnormalities. Maternal nutrition, particularly folic acid, a B vitamin, is crucial in the etiology of NTDs. FA plays a key role in DNA methylation, synthesis, and repair, acting as a cofactor in one-carbon transfer reactions essential for neural tube development. Randomized trials have shown that FA supplementation during preconceptional and periconceptional periods reduces the incidence of NTDs by nearly 80%. Consequently, it is recommended that all women of reproductive age take 400 µg of FA daily. Many countries have introduced FA fortification of staple foods to prevent NTDs, addressing the high rate of unplanned pregnancies. These policies have increased FA intake and decreased NTD incidence. Although the precise mechanisms by which FA protects against NTDs remain unclear, compelling evidence supports its efficacy in preventing most NTDs, leading to national recommendations for FA supplementation in women. This review focuses on preconceptional and periconceptional FA supplementation in the female population of the Visegrad Group countries (Slovakia, Czech Republic, Poland, and Hungary). Our findings emphasize the need for a comprehensive approach to NTDs, including FA supplementation programs, tailored counseling, and effective national-level policies.
Infant Passive Protection Against Coronavirus Through Exclusive Breastfeeding: A Cross-Sectional Study
Authors: Amaral Yasmin , Nardi Antonio Egidio , Marano Daniele , Carioca da Costa Ana Carolina , Moreira Maria Elisabeth
Published: December 2024

Background/Objectives: This study aimed to determine the percentage and duration of neutralizing antibodies against the Omicron variant in human milk after vaccination against SARS-CoV-2, considering the three different vaccine technologies approved in Brazil. Methods: A cross-sectional study was conducted with lactating women who received the complete vaccination cycle with available vaccines (AstraZeneca, Pfizer, CoronaVac, and Janssen). The participants resided in Rio de Janeiro, and samples were collected from April to October 2022. Breast milk was analyzed for evidence of neutralizing antibodies using specific assays for the Omicron variant. Results: The results showed that all types of vaccines were effective in inducing neutralizing antibodies in breast milk regardless of the vaccine technology used. There was no significant difference between women receiving two or three doses. Exclusive breastfeeding was significantly associated with higher percentages of neutralizing antibodies in breast milk compared to non-exclusive breastfeeding. Conclusions: These findings reinforce the importance of breastfeeding as a strategy to provide passive protection to infants, especially where vaccination for children under six months of age is not recommended.
Nutrient Intake and Dietary Adequacy Among Rural Tanzanian Infants Enrolled in the Mycotoxin Mitigation Trial
Authors: Kayanda Rosemary A. , Kassim Neema , Ngure Francis M. , Stoltzfus Rebecca J. , Phillips Erica
Published: December 2024

Background: The Mycotoxin Mitigation Trial (MMT) was a community-based cluster-randomized trial designed to assess the effect of dietary aflatoxin (AF) on linear growth. Similar dietary intake between arms was an important component of the trial’s program theory and essential for the trial’s internal validity and interpretation. Objective: This analysis assessed and compared dietary intake by arm within a sub-sample of infants enrolled in the MMT. Methods: Twenty paired clusters (10 per trial arm) out of the 52 MMT clusters were included in this sub-sample. Up to 15 maternal/infant dyads per cluster were randomly selected for a one-time, structured, multi-pass 24 h dietary recall. Data were collected at the midpoint of the trial, when infants were 12 months of age, over 8 calendar months. We evaluated and compared infant nutrient intake and adequacy of energy, protein, lipid, iron, zinc, calcium, and vitamin A between study arms. Nutrient intake by arm was estimated using mixed-level regression models. Results: A total of 282 mothers participated (n = 140 intervention arm and 142 standard of care (SoC) arm). The mean daily intakes of energy and lipid fed to infants were 505 kcal/day (SD = 225.9) and 13 g/day (SD = 6.9), respectively, in the intervention and SoC arms, with no difference between arms. Intervention infants consumed slightly more protein than SoC infants (13.7 v. 12.3 g/day, p = 0.02). Consumption of iron, zinc, calcium, and vitamin A were low and did not differ between arms. Conclusions: At the midpoint of the MMT, energy, lipid, and micronutrient intake did not differ between arms. Protein consumption was slightly greater in the intervention arm. Guided by the trial’s program theory, this analysis advances the interpretation of the MMT trial findings.
The Etiology of Reduced Muscle Mass with Surgical and Pharmacological Weight Loss and the Identification of Potential Countermeasures
Authors: Faria Isabella , Samreen Sarah , McTaggart Lauren , Arentson-Lantz Emily J. , Murton Andrew J.
Published: December 2024

Obesity represents a major health crisis in the United States, significantly increasing risks for chronic diseases and generating substantial economic costs. While bariatric surgery and pharmacological interventions such as GLP-1 receptor agonists have been proven effective in achieving substantial weight loss and improving comorbid conditions, they also raise concerns about the unintended loss of fat-free mass, particularly muscle. This loss of muscle mass compromises physical functionality, quality of life, and long-term metabolic health, particularly in individuals with sarcopenic obesity or those at risk of frailty. To sustain strength, mobility, and metabolic function during weight loss interventions, the preservation of muscle mass is essential. However, current weight-loss strategies often fail to adequately address the need to maintain fat-free mass. This review explores the physiological mechanisms governing muscle mass, the impact of obesity and rapid weight loss on muscle protein turnover, and nutritional and age-based strategies that may help protect muscle during intentional weight reduction. By focusing on these critical countermeasures, this review aims to inform future clinical practice and research initiatives with the long-term goal of achieving effective weight loss through reduction in fat tissue while preserving skeletal muscle mass, enhancing health outcomes, and long-term functionality in patients undergoing significant weight reduction.
The Effect of Activity Tracking Apps on Physical Activity and Glycemic Control in People with Prediabetes Compared to Normoglycemic Individuals: A Pilot Study
Authors: Kalampoki Aikaterini , Ntzani Evangelia E. , Asimakopoulos Alexandros-Georgios I. , Liberopoulos Evangelos , Tentolouris Nikolaos , Anastasiou Georgia , Adamidis Petros-Spyridonas , Kotsa Kalliopi , Rizos Evangelos C.
Published: December 2024

Introduction—Aim: Adopting a lifestyle that incorporates regular physical activity confers substantial benefits to both physical and mental health and is recommended for prediabetic individuals. The aim of this study is to investigate the impact of activity tracking apps on increasing physical activity and its effect on glycemic control in people with prediabetes. Materials and Methods: This pilot study included 37 participants, 18 in the prediabetic group and 19 in the normoglycemic group matched for age and gender (mean age 53 years, 40% males). Participants used the Google Fit app for 3 months. The number of daily steps was recorded via the app, and blood and urine tests as well as body fat measurements were conducted before and following 3 months of app use. The co-primary outcome was the change in steps, and the change in HbA1c in both groups. Secondary outcomes were the change in fasting plasma glucose (FPG) (main secondary outcome), as well as lipid parameters, body mass index, visceral fat, and kidney function indices among the two groups. Results: Both groups increased the daily step count following the app intervention, without any statistically significant difference when we compared the steps change between the two groups. We found a statistically significant difference between HbA1c levels in favor of the prediabetic compared to the normoglycemic group [mean difference (MD) 0.16, 95%CI 0.04, 0.28, p-value 0.01)], following the 3-month intervention. Additionally, there was a statistically significant difference between FPG levels in favor of the prediabetic compared to the normoglycemic group (MD 9.06, 95%CI 4.16, 13.96, p-value 0.001). Conclusions: The present study suggests that the use of activity tracking apps, combined with tailored activity goals and monthly supportive phone calls, may contribute to improved glycemic control among individuals with prediabetes.
Dietary Macronutrient Composition and Risk of Radiation-Induced Acute Skin Toxicity in Women with Breast Cancer: Results from the ATHENA Project
Authors: Sharma Sukshma , Bracone Francesca , Di Castelnuovo Augusto , Ruggiero Emilia , De Curtis Amalia , Deodato Francesco , Macchia Gabriella , Boccardi Mariangela , Cilla Savino , Morganti Alessio Giuseppe , Cerletti Chiara , de Gaetano Giovanni , Petroni Katia , Tonelli Chiara , Donati Maria Benedetta , Iacoviello Licia , Bonaccio Marialaura ,   on behalf of the EU-ATHENA Trial Investigators
Published: December 2024

Background: The impact of the dietary macronutrient composition and its subcomponents (saccharides, fatty acids, and protein sources) on radiation-induced acute skin toxicity (AST) in breast cancer (BC) patients is unknown. Hence, we examined the association between dietary macronutrients and their subcomponents and the risk of ≥grade 2 (G2) AST post-radiotherapy among women with BC. Methods: An observational study was conducted among 161 BC patients treated with radiotherapy and enrolled in the ATHENA project in Italy. Habitual dietary intake was assessed at study entry (T0) using a 188-item food frequency questionnaire (FFQ). AST was measured at T1 (after 3 or 5 weeks of radiotherapy) and defined according to the Radiation Therapy Oncology Group criteria. A prospective analysis used multivariable-adjusted logistic regression models to examine the association between the dietary macronutrient composition and its subcomponents at T0 and the odds of ≥G2 AST post-radiotherapy. Results: ≥G2 AST post-radiotherapy was observed in 43 (27%) patients. Among dietary macronutrient models, a higher intake of dietary carbohydrates was positively associated with a 30% higher odds of ≥G2 AST post-radiotherapy (OR = 1.30; 95% CI 1.01 to 1.67; for 30 g/d). Conversely, a higher dietary protein intake was inversely associated with a 76% lower odds of ≥G2 AST post-radiotherapy (OR = 0.24; 95% CI 0.06 to 0.91; for 30 g/d). There was no association with dietary fat. In macronutrient subcomponent models, only animal protein was inversely associated with a 51% lower odds of ≥G2 AST post-radiotherapy (0.49; 95% CI 0.25 to 0.95; for 15 g/d). Conclusions: Dietary carbohydrates were associated with a higher risk of radiation-induced AST among women with BC, whereas dietary protein, especially animal protein, was associated with a lower risk. Cautiously balancing carbohydrate and protein intakes could be a part of the clinical management strategy for ≥G2 AST reduction post-radiotherapy among BC women.
Associations Between Hemoglobin and Serum Iron Levels and the Risk of Mortality Among Patients with Coronary Artery Disease
Authors: Li Qing , Pan Zhijun , Zeng Yupeng , Wang Xu , Li Dan , Yin Ting , Chen Qian , Ling Wenhua
Published: December 2024

Background: This study aimed to investigate the relationship between hemoglobin and serum iron levels and mortality risk in patients with coronary artery disease (CAD). Methods: We analyzed data from 3224 patients with CAD using Cox proportional hazards regression models to assess the association of hemoglobin and serum iron levels with cardiovascular and all-cause mortality from the Guangdong coronary artery disease cohort. Results: Over a median follow-up period of 8.9 years, 636 patients died, including 403 from cardiovascular causes. Higher hemoglobin and serum iron levels were linked to a reduced risk of cardiovascular and all-cause mortality. Patients in the highest quartiles of hemoglobin and serum iron levels had multivariable-adjusted hazard ratios (HRs) of 0.62 (95% CI, 0.46–0.85) and 0.51 (95% CI, 0.37–0.69) for cardiovascular mortality and 0.64 (95% CI, 0.50–0.83) and 0.67 (95% CI, 0.53–0.85) for all-cause mortality, compared with those in the lowest quartile. A one-standard-deviation increase in hemoglobin and serum iron levels corresponded to a 19% and 24% reduction in cardiovascular mortality risk and a 19% reduction in all-cause mortality risk for both factors. Restricted cubic spline analysis revealed L-shaped and U-shaped associations between hemoglobin and serum iron levels and cardiovascular and all-cause mortality, respectively. Conclusions: Hemoglobin and serum iron levels were significantly associated with lower risks of cardiovascular and all-cause mortality in patients with CAD. Further research is needed to evaluate the effects of iron supplementation in these patients.
Dietary Counseling: An Option to Malnutrition and Masticatory Deficiency in Patients with Total Protheses? A Scoping Review
Authors: Cifuentes-Suazo Gloria , Alarcón-Apablaza Josefa , Jarpa-Parra Marcela , Venegas Camila , Marinelli Franco , Fuentes Ramón
Published: December 2024

Given the rising global population of older adults and their association with edentulism and the use of complete removable prostheses [CRP], it is imperative to pursue solutions for issues such as the relationship between poor diets and masticatory deficiency. Objective: To examine the research on the efficacy of dietary counseling in enhancing mastication and nutrition in older adults with CRP. Methods: A systematic literature review was performed in the PubMed, Trip, and Web of Science databases. Results: 812 results were retrieved from the databases, from which 6 clinical studies that fulfilled the qualifying criteria were selected. The selected studies reported reduced nutrition in patients with CRP due to impaired masticatory function. Research suggests that employing basic dietary guidelines or simplified nutritional recommendations enhances the masticatory function of patients with CRP, thereby ensuring sufficient nutritional intake. Conclusion: Dietary counseling improves nutritional intake and masticatory function in patients with CRP. This would allow simple dietary advice to be given to patients with total prostheses in clinical practice. Further randomized clinical trials are recommended to increase the available evidence.
Ghrelin Promotes Lipid Uptake into White Adipose Tissue via Endothelial Growth Hormone Secretagogue-Receptor in Mice
Authors: Urai Hidenori , Azegami Tatsuhiko , Komatsu Motoaki , Takahashi Rina , Kubota Yoshiaki , Hasegawa Kazuhiro , Tokuyama Hirofumi , Wakino Shu , Hayashi Kaori , Kanda Takeshi , Itoh Hiroshi
Published: December 2024

Background/Objectives: Endothelial peroxisome proliferator-activated receptor gamma (PPARγ) regulates adipose tissue by facilitating lipid uptake into white adipocytes, but the role of endothelial lipid transport in systemic energy balance remains unclear. Ghrelin conveys nutritional information through the central nervous system and increases adiposity, while deficiency in its receptor, growth hormone secretagogue-receptor (GHSR), suppresses adiposity on a high-fat diet. This study aims to examine the effect of ghrelin/GHSR signaling in the endothelium on lipid metabolism. Methods: We compared the effects of ghrelin on adiposity and lipid uptake into adipocytes in wild-type and GHSR-null mice. Transgenic mice expressing GHSR selectively in endothelial cells were also generated and compared with global GHSR-null and wild-type mice. The impact of ghrelin on lipid uptake-related genes was assessed in cultured endothelial cells. Results: Ghrelin increased adiposity and triglyceride clearance in wild-type but not in GHSR-null mice. GHSR-null mice showed higher serum triglyceride after olive oil gavage and lower white adipose tissue (WAT) weight on a high-fat diet, suggesting impaired lipid uptake. Restoring GHSR expression in endothelial cells increased lipoprotein lipase activity, lipid uptake into WAT, and WAT weight. Ghrelin enhanced free fatty acid uptake and the expression of lipid uptake genes in cultured endothelial cells, whereas these effects were absent in GHSR-null mice-derived endothelial cells. Knockdown of PPARγ revealed that ghrelin/GHSR signaling in endothelial cells promoted lipid uptake via endothelial PPARγ. Conclusions: Endothelial GHSR is key for regulating lipid metabolism via PPARγ in response to ghrelin and for the role of endothelium in regulating white adipocyte metabolism. Targeting endothelial ghrelin signaling may be a promising therapeutic approach for managing excessive adiposity and associated metabolic disorders.
Diet and Lifestyle Factors and Incident Acute Mesenteric Ischemia—A Prospective Cohort Study
Authors: Soltanzadeh-Naderi Yasmin , Acosta Stefan
Published: December 2024

Background/Objectives: Acute mesenteric ischemia (AMI) is life-threatening and difficult to diagnose in time. Unlike many cardiovascular diseases, the association between lifestyle factors such as diet, alcohol consumption, and physical activity and AMI is unknown. Methods: This study is a prospective cohort study with 28,098 middle-aged participants with a mean follow-up time of 23.1 years. Baseline characteristics were obtained with questionnaires regarding physical activity, lifestyle, and diet. The primary endpoint was a diagnosis of AMI identified through the Swedish National Patient Register. Follow-up times were decided by the date of diagnosis, death, or end of follow-up, 2022-12-31. Results: The total number of patients with AMI was 140. Current smoking (adjusted hazard ratio [aHR] 3.02, 95% confidence interval [CI] 1.91–4.79) and those with the highest alcohol consumption (aHR 2.53, 95% CI 1.27–5.03) had a higher risk of developing AMI. Participants with high physical activity, 25.1–50.0 metabolic equivalent task hours per week (MET-h/week), had a lower risk (aHR 0.51, 95% CI 0.27–0.95). Diet quality and dietary components did not affect the risk of AMI. Conclusions: Smoking and higher alcohol consumption were associated with higher risk, while physical activity was associated with lower risk of AMI in this prospective cohort. Diet quality and dietary components were less relevant for the prediction of AMI than these traditional risk factors of atherosclerotic disease.
Cell Membrane Fatty Acids and PIPs Modulate the Etiology of Pancreatic Cancer by Regulating AKT
Authors: Torres Carolina , Mancinelli Georgina , Chen Jee-Wei , Cordoba-Chacon Jose , Pins Danielle , Saeed Sara , McKinney Ronald , Castellanos Karla , Orsi Giulia , Singhal Megha , Patel Akshar , Acebedo Jose , Coleman Adonis , Heneche Jorge , Yalagala Poorna , Subbaiah Papasani , Leal Cecilia , Grimaldo Sam , Ortuno Francisco , Bishehsari Faraz , Grippo Paul
Published: December 2024

Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the worst solid malignancies in regard to outcomes and metabolic dysfunction leading to cachexia. It is alarming that PDAC incidence rates continue to increase and warrant the need for innovative approaches to combat this disease. Due to its relatively slow progression (10–20 years), prevention strategies represent an effective means to improve outcomes. One of the risk factors for many cancers and for pancreatic cancer in particular is diet. Hence, our objective is to understand how a diet rich in ω3 and ω6 polyunsaturated fatty acids affects the progression of this disease. Methods: We investigated polyunsaturated fatty acid (PUFA) effects on disease progression employing both in vitro (PDAC cell lines) and in vivo (EL-Kras and KC mice) approaches. Also, we gathered data from the National Health and Nutrition Examination Survey (NHANES) and the National Cancer Institute (NCI) from 1999 to 2017 for a retrospective observational study. Results: The consumption of PUFAs in a patient population correlates with increased PDAC incidence, particularly when the ω3 intake increases to a lesser extent than ω6. Our data demonstrate dietary PUFAs can be incorporated into plasma membrane lipids affecting PI3K/AKT signaling and support the emergence of membrane-targeted therapies. Moreover, we show that the phospholipid composition of a lipid nanoparticle (LNP) can impact the cell membrane integrity and, ultimately, cell viability after administration of these LNPs. Conclusions: Cancer prevention is impactful particularly for those with very poor prognosis, including pancreatic cancer. Our results point to the importance of dietary intervention in this disease when detected early and the potential to improve the antiproliferative effect of drug efficacy when combined with these regimens in later stages of pancreatic cancer.
Cytokine and Chemokine Responses of Peripheral Blood Mononuclear Cells from Dogs Infected with Mycobacterium bovis
Authors: Morrison Tyler , Gunn-Moore Danielle A. , Hope Jayne C. , O’Halloran Conor
Published: December 2024

Mycobacterial infections are an important emerging zoonosis in companion animals for which diagnostic options remain imperfect, and the canine immunological response to these infections has been poorly investigated. We sought to further define the cellular response of peripheral blood mononuclear cells (PBMCs) from dogs infected with Mycobacterium bovis, as determined using a commercial interferon-gamma response assay (IGRA). To this end, PBMCs from healthy or infected dogs were collected. Serum samples were tested to further classify dogs as seropositive or seronegative for circulating antibodies against M. bovis using the DPP® VetTB Assay, Idexx M. bovis antibody ELISA, and a novel purified protein derivative ELISA. Isolated PBMCs were stimulated with mycobacterial proteins (PPDB or ESAT-6/CFP-10), and 13 cytokines/chemokines were measured in the supernatant. These concentrations were determined using the CYTOMAG-90K MILLIPLEX MAP Canine Cytokine/Chemokine system. PBMCs from infected dogs released IFN-γ in response to stimulation, but this response was reduced in those that had seroconverted. Similarly, cells stimulated with PPDB secreted increased amounts of TNF-α when dogs were seronegative, but cells taken from seropositive dogs did not. Finally, the IL-18 response of seropositive dogs was reduced compared to those that were seronegative in response to PPDB, potentially suggesting that these dogs have a reduced macrophage functionality. This work demonstrates that the inflammatory cytokine response may wane following seroconversion with deleterious consequences for the host response. Overall, combining IFN-γ and TNF-α assessment during diagnosis may increase IGRA sensitivity, whilst further work is needed to better understand the prognostic and diagnostic implications of seroconversion in dogs.
Differentiation of Escherichia coli and Shigella flexneri by Metabolite Profiles Obtained Using Gold Nanoparticles-Based Surface-Assisted Laser Desorption/Ionization Mass Spectrometry
Authors: Arendowski Adrian
Published: December 2024

Escherichia coli and Shigella flexneri are challenging to differentiate using methods such as phenotyping, 16S rRNA sequencing, or protein profiling through matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS) due to their close relatedness. This study explores the potential for identifying E. coli and S. flexneri by incorporating reference spectra of metabolite profiles, obtained via surface-assisted laser desorption/ionization mass spectrometry (SALDI MS) employing gold nanoparticles (AuNPs), into the Bruker Biotyper database. Metabolite extracts from E. coli and S. flexneri cells were prepared using liquid–liquid extraction in a chloroform–methanol–water system. The extracts were analyzed using Au-SALDI MS in positive ion mode, and reference spectra, compiled from 30 spectra for each bacterium, were added to the database. Identification of bacteria based on metabolite fingerprints in the Biotyper database produced correct results with scores exceeding 2.75. The results of Partial Least Squares-Discriminant Analysis (PLS-DA) demonstrated that the metabolomic approach could accurately differentiate the microorganisms under study. A panel of nine m/z values was also identified, each with an area under the ROC curve of above 0.8, enabling accurate identification of E. coli and S. flexneri. A search of metabolite databases allowed the following compounds to be assigned to the selected m/z values: N-acetylputrescine, arginine, 2-maleylacetate, benzoyl phosphate, N8-acetylspermidine, alanyl-glutamate, 4-hydroxy-2,3,4,5-tetrahydrodipicolinate, and sucrose. The analyses showed that identification of bacteria based on metabolite profiles obtained by the Au-SALDI MS method is feasible and can be useful for distinguishing closely related microorganisms that are difficult to differentiate by other techniques.
Advances and Challenges in Antiviral Development for Respiratory Viruses
Authors: De Jesús-González Luis Adrián , León-Juárez Moisés , Lira-Hernández Flor Itzel , Rivas-Santiago Bruno , Velázquez-Cervantes Manuel Adrián , Méndez-Delgado Iridiana Monserrat , Macías-Guerrero Daniela Itzel , Hernández-Castillo Jonathan , Hernández-Rodríguez Ximena , Calderón-Sandate Daniela Nahomi , Mata-Martínez Willy Salvador , Reyes-Ruíz José Manuel , Osuna-Ramos Juan Fidel , García-Herrera Ana Cristina
Published: December 2024

The development of antivirals for respiratory viruses has advanced markedly in response to the growing threat of pathogens such as Influenzavirus (IAV), respiratory syncytial virus (RSV), and SARS-CoV-2. This article reviews the advances and challenges in this field, highlighting therapeutic strategies that target critical stages of the viral replication cycle, including inhibitors of viral entry, replication, and assembly. In addition, innovative approaches such as inhibiting host cellular proteins to reduce viral resistance and repurposing existing drugs are explored, using advanced bioinformatics tools that optimize the identification of antiviral candidates. The analysis also covers emerging technologies such as nanomedicine and CRISPR gene editing, which promise to improve the stability and efficacy of treatments. While current antivirals offer valuable options, they face challenges such as viral evolution and the need for accessible treatments for vulnerable populations. This article underscores the importance of continued innovation in biotechnology to overcome these limitations and provide safe and effective treatments. Combining traditional and advanced approaches in developing antivirals is essential in order to address respiratory viral diseases that affect global health.
Evaluation of the Antioxidant Properties and Biological Effects of a Novel Combined Barberry Root–Propolis Extract on HEK293T Cells
Authors: Marcinčáková Dana , Hudáková Nikola , Miłek Michal , Kolesárová Mária , Dżugan Małgorzata , Cizkova Dasa , Legáth Jaroslav
Published: December 2024

Background/Objectives: The health benefits of honeybee products and herbs are well known, and their appropriate combination may enhance their biological efficacy. This study investigated the biological properties of a combined barberry root and propolis extract (PBE) in comparison to a propolis extract (PE), a barberry root extract (BE), and pure berberine (BN). Methods: The antioxidant properties were evaluated using DPPH and FRAP methods and total phenolic contents (TPC) were assessed by the Folin–Ciocalteu method. HPTLC was used to quantify the BE in the tested samples. Their effect on HEK293T cells was monitored in real-time by using the xCELLigence system which recorded changes in the proliferative activity (PA). The metabolic activity (MA) was evaluated using an MTS test and cell migration was analyzed via a scratch assay. Results: The PE exhibited a higher TPC (198.67 mg/g) than the BE (119.3 mg/g). The PBE exhibited a comparable antioxidant effect to that of the PE. In the cell assays, the PE, the BE, and BN significantly reduced the proliferative activity at higher concentrations (p < 0.0001) while the PBE demonstrated a lower cytotoxicity and proved to be safer for the tested cells. The highest IC50 value was determined for the PBE (130 µg/mL), suggesting that this combination has a reduced cytotoxicity. However, the scratch test did not confirm a significant supportive effect of the PBE on cell migration. Conclusions: Although the PBE did not show enhanced antioxidant properties, it may mitigate cytotoxicity and support proliferation at lower concentrations. This suggests that extraction of raw propolis with a previously prepared barberry extract results in a safer preparation, but its therapeutic potential requires further studies using biological models.
Fabrication and In Vivo Evaluation of In Situ pH-Sensitive Hydrogel of Sonidegib–Invasomes via Intratumoral Delivery for Basal Cell Skin Cancer Management
Authors: Ghalwash Maha M. , Fouad Amr Gamal , Mohammed Nada H. , Nagib Marwa M. , Khalil Sherif Faysal Abdelfattah , Belal Amany , Miski Samar F. , Albezrah Nisreen Khalid Aref , Elsayed Amani , Hassan Ahmed H. E. , Roh Eun Joo , El-Housiny Shaimaa
Published: December 2024

Background/Objectives: Basal cell skin cancer (BCSC) develops when skin cells proliferate uncontrollably. Sonidegib (SDB) is a therapeutic option for the treatment of BCSC by inhibiting hedgehog signaling. The problems with SDB’s low solubility, poor bioavailability, resistance, poor targeting, and first-pass action make it less effective when taken orally. This investigation set out to design an intratumoral in situ pH-sensitive hydrogel of SDB-invasomes (IPHS-INV) that can effectively treat BCSC by improving SDB’s bioavailability, sustainability, targeting, and efficacy while also reducing its resistance and undesirable side effects. Methods: Numerous S-INV formulations were developed using Box–Behnken Design Expert and tested before settling on the optimum S-INV formulation. An experimental 7, 12-dimethylbenzanthracene (DMBA) carcinoma rat model was used for in vivo studies of the IPHS-INV formulation after it was combined with chitosan. Results: Phospholipids (1.72% w/w), cholesterol (0.15% w/w), ethanol (1% v/v), and cineole (1.5% v/v) were shown to be the optimal components in the SDB-invasome formulation. The IPHS-INV formulation outperformed the permeation and bioavailability of free SDB by 7.14 and 6 times, respectively, and sustained its release by 57.41%. The IPHS-INV formulation showed a decrease in tumor volume of 99.05% and a reduction of hypercellular tumors, indicating its anti-cancer activity. The intratumoral IPHS-INV formulation maintained a higher concentration of SDB in tumors, indicating its targeting activity. Conclusions: These findings support the use of the intratumoral IPHS-INV formulation as an effective strategy for the treatment of BCSC.
Heart Failure in Elderly Patients: Medical Management, Therapies and Biomarkers
Authors: Nadziakiewicz Paulina , Szczurek-Wasilewicz Wioletta , Szyguła-Jurkiewicz Bożena
Published: December 2024

Heart failure (HF) is a common condition and one of the main morbidity and mortality factors in elderly patients. The incidence of HF progressively increases with age, reaching >10% in those aged 70 years or over. In the elderly population, both the diagnosis and the management of HF prove challenging, often requiring specialized care and a multidisciplinary approach. In seniors, atypical presentation of HF is much more common than in younger patients; thus, a holistic assessment with biomarkers related to HF allows for early diagnosis and accurate risk stratification in this group of patients. This article reviews the clinical and diagnostic differences in elderly patients with HF, highlighting the presence of comorbidities, frailty, cognitive impairment, and polypharmacy, as well as discussing potential biomarkers that may have clinical application in this population.