bluuebunny/crossref_metadata_2025 huggingface dataset:
The Role of Vitamin D Deficiency in Hepatic Encephalopathy: A Review of Pathophysiology, Clinical Outcomes, and Therapeutic Potential
Authors: Johnson Coplen D. , Stevens Christopher M. , Bennett Matthew R. , Litch Adam B. , Rodrigue Eugenie M. , Quintanilla Maria D. , Wallace Eric , Allahyari Massoud
Published: November 2024

Hepatic encephalopathy (HE) is a neuropsychiatric condition frequently associated with cirrhosis and portosystemic shunting (PSS). It imposes a significant clinical and economic burden, with increasing attention toward identifying modifiable factors that could improve outcomes. Emerging evidence suggests that vitamin D deficiency (VDD), prevalent in patients with cirrhosis, may contribute to the development and severity of HE. This review explores the association between VDD and HE by analyzing the underlying pathophysiology, including oxidative stress, ammonia accumulation, and impaired hepatic function. Additionally, we summarize recent studies highlighting the correlation between low serum 25-hydroxy vitamin D (25-OHD) levels and worsening grades of HE. Despite strong observational data, interventional studies on vitamin D (VD) supplementation for HE remains limited. Current evidence suggests that VD’s antioxidant properties may alleviate oxidative stress in HE, with potential benefits in mitigating disease severity. Future research should focus on longitudinal studies and randomized controlled trials to evaluate the clinical impact of VD supplementation on HE outcomes and explore VD’s role in patients undergoing transjugular intrahepatic portosystemic shunt (TIPS) procedures. Understanding the therapeutic potential of VD could lead to improved management strategies for HE and cirrhotic patients at large.
Association of Plant-Based Dietary Patterns with Activities of Daily Living Disability in Older Adults Based on a 10-Year Cohort Study
Authors: Cai Dahuan , Zeng Yanxin , Liang Xiao , Song Anchao , Ye Mengliang
Published: November 2024

Background: In the context of population aging, activities of daily living (ADL) disability has brought great challenges to the health of the elderly. The relationship between plant-based dietary patterns and the health of the elderly has been widely discussed. However, few studies have explored the correlation between plant-based dietary patterns and ADL disability in older adults. Methods: We included 2004 participants from the Chinese Longitudinal Health Longevity Survey (CLHLS). The Simplified Food Frequency Questionnaire was used to measure Plant-Based Diet Index (PDI), healthy Plant-Based Diet Index (hPDI), and unhealthy Plant-Based Diet Index (uPDI). A Cox proportional hazards model was used to assess associations between plant-based dietary patterns and ADL disability in older adults and to explore age differences in these associations. Results: uPDI and hPDI showed nonlinear associations with ADL disability. Following covariate adjustments, older adults in the highest tertile of the hPDI have a lower risk of ADL disability than those in the lowest tertile (HR = 0.61). Older adults in the highest tertile of the uPDI have a higher risk of ADL disability than those in the lowest tertile (HR = 1.33). Subgroup analyses showed that hPDI was more protective against ADL disability in those under 80 years of age, whereas uPDI was only significantly associated with an increased risk of ADL disability in those under 80 years of age. Conclusions: Increasing the intake of healthy plant-based diets and reducing the intake of unhealthy plant-based and animal-based diets can help prevent and improve ADL disability in the elderly.
Malnutrition–Inflammation Score of Patients with Chronic Kidney Disease from Early Stage to Initiation of Dialysis
Authors: Lim Lee-Moay , Kuo Hung-Tien , Chao Yu-Lin , Shen Feng-Ching , Chen Yi-Kong , Chiu Yi-Wen , Hwang Shang-Jyh , Hung Chi-Chih
Published: November 2024

Background: The malnutrition–inflammation score (MIS) is a practical and accessible tool for evaluating protein energy wasting (PEW) in patients on dialysis. However, the severity of PEW at each stage of chronic kidney disease (CKD), especially with late dialysis initiation, is unclear. Methods: We evaluated the MIS of 3659 patients with CKD stages 1–5 and the changes in their MIS results at baseline and at the time before dialysis initiation. Patients were defined to have PEW if they had a subjective global assessment (SGA) rating of C or lower. Results: The MIS increased substantially over a follow-up period of 6.12 years for 1124 patients just starting dialysis, with 49.3% having an MIS of 8. The pre-dialysis MIS was associated with baseline MIS, age, cardiovascular disease, and cancer. The prevalence of PEW based on an SGA rating of C or lower increased from 10.5% at baseline to 61.2% immediately before dialysis. The prevalence of PEW based on an MIS of ≥8 increased from 28.5% at baseline to 49.3% immediately before dialysis. In CKD stage 5 patients, 29.4% had PEW based on an MIS of 8 or less, and 11.6% had an SGA rating of C. The MIS was revealed to be associated with renal function, nutritional markers, and cardiometabolic disease (diabetes or cardiovascular disease). Conclusions: In conclusion, the MIS increased as CKD progressed to stages 4 and 5, as well as just prior to dialysis. Our study identified patients who required PEW assessment on the basis of their MIS results.
The Effect of Nutrients on Neurological Disorders
Authors: Perrone Lorena , Grant William B.
Published: November 2024

The prevalence of neurological disorders (NDs) is increasing, with great cost to public health [...]
Phytochemical, Cytoprotective Profiling, and Anti-Inflammatory Potential of Colchicum luteum in Rheumatoid Arthritis: An Experimental and Simulation Study
Authors: Abbasi Huda , Sharif Maria , John Peter , Bhatti Attya , Hayat Muhammad Qasim , Mansoor Qaisar
Published: November 2024

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by severe pain, inflammation, and joint deformity. Currently, it affects 1% of the population, with a projection to exceed 23 million cases by 2030. Despite significant advancements, non-steroidal anti-inflammatory drugs (NSAIDs), the first line of treatment, are associated with a range of adverse effects. Consequently, plant-based derivatives are being utilized as an effective alternative. This study evaluates the anti-inflammatory and safety profile of Colchicum luteum hydroethanolic extract (CLHE) in comparison to NSAIDs, with a focus on COX-2 and TNFα inhibition. Methods: CLHE potential was evaluated by phytochemical screening and in vitro bioactivity assays. Toxicity profile was conducted in Human Colon Epithelial Cells (HCEC) and Balb/c mice. Anti-inflammatory potential was explored in a collagen-induced arthritic (CIA) mice model. Bioactive compounds were identified computationally from GCMS data and subjected to docking and simulation studies against COX2 and TNFα. Results: CLHE demonstrated significant antioxidant (IC-50 = 6.78 µg/mL) and anti-inflammatory (IC-50 = 97.39 µg/mL) activity. It maintained 50% cell viability at 78.5 μg/µL in HCEC cells and exhibited no toxicity at a dose of 5000 mg/kg in mice. In the CIA model, CLHE significantly reduced paw swelling, arthritic scoring, C-reactive protein levels, and spleen indices, outperforming ibuprofen. Expression analysis confirmed the downregulation of COX-2, TNFα, and MMP-9. Histopathological analysis indicated the superior efficacy of CLHE compared to ibuprofen in reducing inflammation, synovial hyperplasia, and bone erosion. Computational studies identified compound-15 (CL15), (4-(4,7-dimethoxy-1,3-benzodioxol-5-yl)-2-oxo pyrrolidine-3-carboxylic acid), a non-toxic compound with strong binding affinities to COX-2 (−12.9 KJ/mol), and TNF-α (−5.8 KJ/mol). Conclusions: The findings suggest the potential of Colchicum luteum as a safer, anti-inflammatory, and multi-targeted alternative to NSAIDs for RA treatment.
The Interplay Between Depression, Probiotics, Diet, Immunometabolic Health, the Gut, and the Liver—A Secondary Analysis of the Pro-Demet Randomized Clinical Trial
Authors: Gawlik-Kotelnicka Oliwia , Rogalski Jakub , Czarnecka-Chrebelska Karolina H. , Burzyński Jacek , Jakubowska Paulina , Skowrońska Anna , Strzelecki Dominik
Published: November 2024

(1) Background: Depression, metabolic alternations, and liver diseases are highly comorbid. Studies have shown that probiotics might be helpful in the treatment of the above-mentioned states. The aim of this secondary analysis was to search for possible predictors of probiotics’ efficacy on liver-related outcome measures. (2) Methods: Data from 92 subjects from a randomized clinical trial on the effect of probiotics on depression were analyzed. The shift in liver steatosis and fibrosis indices was assessed in the context of baseline immunometabolic, psychometric, dietary, and intestinal permeability factors. Correlation analysis and linear regression models were used. (3) Results: A total of 30% of the variance of the improvement in the score of the aspartate transferase to platelet ratio index was explained by probiotic use, higher pre-intervention triglycerides, cholesterol, C-reactive protein levels, increased cereal intake, and a lower consumption of sweets. Then, the model of the change in alanine transferase indicated that probiotics were efficient when used by subjects with higher basal levels of intestinal permeability markers. (4) Conclusions: Probiotics being used along with a healthy diet may provide additional benefits, such as decreased cardiovascular risk, for patients with measures consistent with the immunometabolic form of depression. Probiotic augmentation may be useful for liver protection among subjects with a suspected “leaky gut” syndrome. ClinicalTrials.gov: NCT04756544.
Using Participatory Narrative Inquiry to Assess Experiences and Self-Experimentation with Diet Interventions in Inflammatory Bowel Disease Patients
Authors: Hos Celine , Tebbens Merel , Bezema Tjitske , Bosch Jos A. , Kraneveld Aletta D. , Spooren Corinne E. G. M. , de Haas Marie Claire , Stokkers Pieter C. F. , Duijvestein Marjolijn , Bouma Gerd , te Velde Anje A.
Published: November 2024

Background and Aims: To improve quality of life (QoL), patients with inflammatory bowel diseases (Crohn’s disease and ulcerative colitis) often self-experiment with lifestyle changes such as dietary modifications. The nature (e.g., type of interventions, expectations, perceived efficacy) of these single-subject experiments has not been systematically investigated. Method: We used Participatory Narrative Inquiry (PNI), a structured qualitative method, to obtain information about these experiments through patient stories. Results: We demonstrate that PNI can be a method to collect and analyze IBD patient ideas and experiences regarding lifestyle and nutritional factors in a structured manner to reveal valuable insights for personal and scientific follow-up research. Patients report rest, (psychological) balance, and a change in diet when describing times when they experienced a better QoL. When focusing on diet, patients reported a considerable number of food products that were experienced as beneficial by one person but detrimental by another. Conclusions: PNI is a suitable method to obtain information about self-experimentation. An insight that was attained was that personalized (dietary) guidance that supports the individual is needed.
Gut Microbiota Modulates Fgf21 Expression and Metabolic Phenotypes Induced by Ketogenic Diet
Authors: Wei Xinyi , Lu Yunxu , Hong Shangyu
Published: November 2024

Background: The ketogenic diet (KD) is a widely used intervention for obesity and diabetes, effectively reducing body weight and blood glucose levels. However, the molecular mechanisms by which the KD influences body weight and glucose metabolism are not fully understood. While previous research has shown that the KD affects the gut microbiota, the exact role of microbiota in mediating its metabolic effects remains unclear. Methods: In this study, we used antibiotics to eliminate the gut microbiota, confirming its necessity for the KD’s impact on weight loss and glucose metabolism. We also demonstrated the significant role of FGF21 in these processes, through antibiotics intervention in Fgf21-deficient mice. Results: Furthermore, we revealed that the KD alters serum valine levels via the gut microbiota, which in turn regulates hepatic Fgf21 expression and circulating FGF21 levels through the GCN2-eIF2α-ATF5 signaling pathway. Additionally, we demonstrated that valine supplementation inhibits the elevated expression of FGF21, leading to the reduced body weight and improved glucose metabolism of the KD-fed mice. Overall, we found that the gut microbiota from the KD regulates Fgf21 transcription via the GCN2-eIF2α-ATF5 signaling pathway. ultimately affecting body weight and glucose metabolism. Conclusion: Our findings highlight a complex regulatory network linking the KD, Fgf21 expression, and gut microbiota, offering a theoretical foundation for targeted therapies to enhance the metabolic benefits of the KD.
A Porcine-Derived Heme Iron Powder Restores Hemoglobin in Anemic Rats
Authors: Swain James H. , Glosser Logan D.
Published: November 2024

Background/Objectives: Iron-fortified foods reduce the incidence of iron deficiency anemia. However, the nutritional efficacy of heme iron fortificants is unclear. Methods: In this study, we determined the hemoglobin regeneration efficiency (HRE) of a porcine-derived heme iron powder (HIP), treating anemic rats (hemoglobin (Hb) 3–6 g/dL) with 14-day repletion diets fortified with four different concentrations (12, 24, 36, or 48 mg iron/kg diets) of HIP or a control diet (“no added iron”); n = 9–12/group. Results: Our results demonstrate an inverse association between HRE and increasing dietary iron from the HIP. The HRE ratios of diets containing the HIP powder at 12, 24, 36, or 48 mg iron/kg were 0.508, 0.268, 0.273, and 0.223, respectively. Based on the mean final Hb values at 14 d, the HRE ratio of the 12 mg iron/kg diet was significantly higher (p ≤ 0.05) compared to the other HIP diet groups; however, only the HIP provided in the 36 and 48 mg iron/kg diets restored hemoglobin to high enough levels (mean Hb > 6 g/dL) to correct anemia. Conclusions: Our findings show that HIP at each of the concentrations tested increased Hb; moreover, when present at higher concentrations in the diet, the HIP is capable of restoring hemoglobin to resolve iron deficiency anemia.
Fresh-Cooked but Not Cold-Stored Millet Exhibited Remarkable Second Meal Effect Independent of Resistant Starch: A Randomized Crossover Trial
Authors: Peng Xiyihe , Fan Zhihong , Wei Jinjie , Liu Rui , Lou Xinling , Hu Jiahui , Xing Yuqing
Published: November 2024

It is well established that cold storage results in increased resistant starch and a reduced glycemic index in carbohydrate food. However, the effects of cold storage on the glycemic response of the second meal of cereals remain unclear. The aim of this study was to compare the postprandial glycemic responses between the paired glutinous and non-glutinous grains, either fresh-cooked or refrigerated, after both the first and second meals. In this randomized crossover trial, eighteen healthy female participants consumed eight test meals, each containing 50 g of carbohydrate, including fresh-cooked non-glutinous and glutinous rice, non-glutinous and glutinous millet, and their refrigerated counterparts (4 °C for 24 h). Postprandial blood glucose and insulin were measured at 240 min and 120 min after breakfast. After a standard lunch, the participants’ blood glucose concentrations were measured within 180 min. The rapidly digestible starch (RDS), slowly digestible starch (SDS), and resistant starch (RS) contents of the samples were determined by in vitro enzymatic analysis. Cold-stored non-glutinous rice (CR) and cold-stored non-glutinous millet (CM) had a 24.4% and 29.5% lower incremental area under the curve (iAUCglu) of glucose within 240 min compared to the control (fresh-cooked rice non-glutinous, FR), respectively (p < 0.05). There were no significant differences between either the cold or hot glutinous grains and FR with respect to postprandial glycemic and insulinemic parameters. After a standard lunch, the fresh-cooked non-glutinous millet (FM) achieved a 39.1% lower iAUCglu0–180 compared to the FR (p < 0.05). FM had the highest percentage of SDS (64.8%, p < 0.05) among all grain samples. Refrigeration treatment reduced the glycemic excursion only in non-glutinous grains at the first meal, but the FM instead of CM demonstrated a significant second meal effect.
Nutritional Inequality and Co-Morbid Chronic Disease Among Breast Cancer Survivors in China
Authors: Xia Juan , Yu Jinming , Qu Lindi , Lv Lin , Zhu Wenyu , Meng Xinyu , Shao Jian , Luo Yanxia
Published: November 2024

Background/Objectives: Breast cancer survivors often face an elevated risk of developing co-morbid chronic diseases, which may be exacerbated by nutritional inequalities. This study aimed to comprehensively assess the associations between nutrition literacy, dietary quality, and the risk of co-morbidity in breast cancer survivors in China. Methods: A cross-sectional study was conducted among cancer survivors enrolled in the Shanghai Cancer Rehabilitation Club from March to July 2023. The multivariable models of logistic regression, Poisson regression, and mediation analysis were used to explore the relationship between nutrition literacy, dietary quality, and co-morbid chronic diseases among breast cancer survivors in China. Results: The mean age of the 1552 female breast cancer survivors was 64.5 ± 7.02 years. Nutrition literacy was found to be low, with 49.81% of participants scoring above the threshold for adequate nutrition literacy. The median (IQR) diet quality distance, low bound score, and high bound score were 67.0 (55.0, 81.0), −39.0 (−51.0, −28.0), and 25.0 (16.0, 36.0), respectively. Of the total female breast cancer survivors, 67.27% were reported to have at least one comorbid chronic disease. Hypertension (37.32%) was the most common co-morbid chronic disease. Each score increase of 10 in nutrition literacy (AOR 0.88, 95%CI 0.808–0.962) was associated with a significant reduction in co-morbid chronic disease risk among breast cancer survivors. Poisson regression analysis of the number of chronic diseases was conducted, and consistently, an association between higher nutrition literacy levels and fewer chronic diseases was observed (AOR 0.94, 95%CI 0.911–0.971). The indirect effect of nutrition literacy on comorbidity risk through dietary quality was not significant (indirect effect = 0.994, 95%CI = 0.980–1.008). Conclusions: Nutrition literacy is paramount in breast cancer survivors’ dietary quality and prognosis. Enhancing nutrition literacy may be a crucial strategy for improving dietary quality and mitigating the risk of comorbid chronic diseases in this vulnerable population.
Myokines and Microbiota: New Perspectives in the Endocrine Muscle–Gut Axis
Authors: Saponaro Federica , Bertolini Andrea , Baragatti Riccardo , Galfo Leonardo , Chiellini Grazia , Saba Alessandro , D’Urso Giuseppina
Published: November 2024

This review explores the dual role of skeletal muscle as both a mechanical and endocrine organ, highlighting its contributions to overall health and its adaptability to various inputs such as nutrition, hormones, exercise, and injuries. In addition to its role in metabolism and energy conversion, skeletal muscle secretes signalling molecules called myokines (at rest) and exerkines (during/after physical exercise), which communicate with other organs like the brain, the cardiovascular system, and the immune system. Key molecules such as interleukins, irisin, and myostatin are discussed for their roles in mediating muscle health and inter-organ communication. This work also focuses on the muscle–gut axis, emphasising the bidirectional interaction between skeletal muscle and the gut microbiota, a complex ecosystem influencing immune defence, digestion, and metabolism. Muscle activity, particularly exercise, alters the gut microbial composition, promoting beneficial species, while gut-derived metabolites like short-chain fatty acids (SCFAs) impact muscle metabolism, mitochondrial function, and insulin sensitivity. Dysbiosis, or an imbalanced microbiota, can lead to muscle atrophy, inflammation, and metabolic dysfunction. This evidence highlights emerging research into myokines and exerkines as potential therapeutic targets for managing conditions like muscle decline, ageing, and metabolic diseases through muscle–gut interactions.
Biomarker-Guided Dietary Supplementation: A Narrative Review of Precision in Personalized Nutrition
Authors: Pokushalov Evgeny , Ponomarenko Andrey , Shrainer Evgenya , Kudlay Dmitry , Miller Richard
Published: November 2024

Background: Dietary supplements (DS) are widely used to address nutritional deficiencies and promote health, yet their indiscriminate use often leads to reduced efficacy, adverse effects, and safety concerns. Biomarker-driven approaches have emerged as a promising strategy to optimize DS prescriptions, ensuring precision and reducing risks associated with generic recommendations. Methods: This narrative review synthesizes findings from key studies on biomarker-guided dietary supplementation and the integration of artificial intelligence (AI) in biomarker analysis. Key biomarker categories—genomic, proteomic, metabolomic, lipidomic, microbiome, and immunological—were reviewed, alongside AI applications for interpreting these biomarkers and tailoring supplement prescriptions. Results: Biomarkers enable the identification of deficiencies, metabolic imbalances, and disease predispositions, supporting targeted and safe DS use. For example, genomic markers like MTHFR polymorphisms inform folate supplementation needs, while metabolomic markers such as glucose and insulin levels guide interventions in metabolic disorders. AI-driven tools streamline biomarker interpretation, optimize supplement selection, and enhance therapeutic outcomes by accounting for complex biomarker interactions and individual needs. Limitations: Despite these advancements, AI tools face significant challenges, including reliance on incomplete training datasets and a limited number of clinically validated algorithms. Additionally, most current research focuses on clinical populations, limiting generalizability to healthier populations. Long-term studies remain scarce, raising questions about the sustained efficacy and safety of biomarker-guided supplementation. Regulatory ambiguity further complicates the classification of supplements, especially when combinations exhibit pharmaceutical-like effects. Conclusions: Biomarker-guided DS prescription, augmented by AI, represents a cornerstone of personalized nutrition. While offering significant potential for precision and efficacy, advancing these strategies requires addressing challenges such as incomplete AI data, regulatory uncertainties, and the lack of long-term studies. By overcoming these obstacles, clinicians can better meet individual health needs, prevent diseases, and integrate precision nutrition into routine care.
Artificial Intelligence Holds Promise for Transforming Public Health Nutrition
Authors: An Ruopeng , Yang Yuanyuan
Published: November 2024

The intersection of artificial intelligence (AI) and public health nutrition is rapidly evolving, offering transformative potential for how we understand, assess, and improve population health [...]
Understanding and Exploring the Food Preferences of Filipino School-Aged Children Through Free Drawing as a Projective Technique
Authors: Bernardino Melvin , Sison Nicole , Bruce Jeanne , Tiribelli Claudio , Rosso Natalia
Published: November 2024

Background and Objectives: Numerous traditional and innovative approaches have been employed to understand and evaluate children’s food preferences and food and nutrition knowledge, recognizing their essential role in shaping good nutrition. Drawing as a projective technique allows children to express their unconscious thoughts and preferences through visual representation, distinguishing it from other methods by providing an insight into their inner feelings and perceptions that may not be easily articulated through verbal techniques. The main goals of the study are to use drawing as a projective technique to gain insights into children’s food preferences, and to examine the children’s current nutrition knowledge and dietary perceptions. Methods: This study involved school-aged children from four public schools in San Jose City, Nueva Ecija, Philippines, who met the inclusion criteria and provided parental consent and the children’s permission. Data collection included (a) questionnaires to measure food group and food frequency knowledge, the children’s opinions on food healthiness and likability, and (b) a drawing activity as a projective technique. The questionnaire scores and the specific foods on the children’s drawings were entered into an electronic worksheet and analyzed quantitatively. Results: The majority of Filipino school-aged children have a low (50%) to average (43%) level of food group knowledge and an average (62%) to low (32%) level of food frequency knowledge. The children can identify the healthiness of the food, but they express a liking for both healthy and unhealthy options. The children’s drawings showed a low preference for Glow food groups, including fruits and vegetables (47%), as compared to Grow foods (94%), Beverages (89%), and Go foods (85%) groups. “Rice and Egg”, the most paired items, indicated a preference among Filipino children. Gender-based analysis showed girls favored “Ice Cream”, “Bread”, “Apple”, and “Oranges” more than boys, but there were no significant gender differences found in Grow food group preferences. Conclusions: Children’s drawings are an effective, valuable complementary tool for understanding children’s food preferences, displaying the value of creative methods in gaining unique insights. The results highlight specific gaps in knowledge, such as the need for a better understanding of food groups and the importance of fruits and vegetables among children. Addressing these gaps in educational programs could enhance children’s food knowledge and encourage healthier dietary choices. Nutrition education programs might use interactive activities focused on food groups and emphasize the benefits of fruits and vegetables to promote better dietary habits for the improvement of children’s long-term health outcomes.
Differential TLR-ERK1/2 Activity Promotes Viral ssRNA and dsRNA Mimic-Induced Dysregulated Immunity in Macrophages
Authors: Shrestha Rakshya , Johnson Paige Marie , Ghimire Roshan , Whitley Cody John , Channappanavar Rudragouda
Published: November 2024

RNA virus-induced excessive inflammation and impaired antiviral interferon (IFN-I) responses are associated with severe disease. This innate immune response, also referred to as “dysregulated immunity” is caused by viral single-stranded RNA (ssRNA)- and double-stranded-RNA (dsRNA)-mediated exuberant inflammation and viral protein-induced IFN antagonism. However, key host factors and the underlying mechanism driving viral RNA-mediated dysregulated immunity are poorly defined. Here, using viral ssRNA and dsRNA mimics, which activate toll-like receptor 7 (TLR7) and TLR3, respectively, we evaluated the role of viral RNAs in causing dysregulated immunity. We observed that murine bone marrow-derived macrophages (BMDMs), when stimulated with TLR3 and TLR7 agonists, induced differential inflammatory and antiviral cytokine response. TLR7 activation triggered a robust inflammatory cytokine/chemokine induction compared to TLR3 activation, whereas TLR3 stimulation induced significantly increased IFN/IFN stimulated gene (ISG) response relative to TLR7 activation. To define the mechanistic basis for dysregulated immunity, we examined cell-surface and endosomal TLR levels and downstream mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-kB) activation. We identified significantly higher cell-surface and endosomal TLR7 levels compared to TLR3, which were associated with early and robust MAPK (p-ERK1/2, p-P38, and p-JNK) and NF-kB activation in TLR7-stimulated macrophages. Furthermore, blocking EKR1/2 and NF-kB activity reduced TLR3/7-induced inflammatory cytokine/chemokine levels, whereas only ERK1/2 inhibition enhanced viral RNA mimic-induced IFN/ISG responses. Collectively, our results illustrate that high cell-surface and endosomal TLR7 expression and robust ERK1/2 activation drive viral ssRNA mimic-induced excessive inflammatory and reduced IFN/ISG response and blocking ERK1/2 activity would likely mitigate viral-RNA/TLR-induced dysregulated immunity.
Inactivation of Lipopolysaccharide-Biosynthesizing Genes Altered Lipids Composition and Intensity in Cronobacter sakazakii
Authors: Hu Xiaoqing , Yang Xi , Wu Shuyan , Lu Xuan , Ma Yuan , Tang Ziyi , Wang Xiaoyuan , Huang Xiaodong , Wang Shuiping
Published: November 2024

Gram-negative bacteria possess an asymmetric outer membrane, where the outer leaflet consists of LPSs and the inner leaflet comprises phospholipids. Cronobacter sakazakii, an opportunistic milk-borne pathogen that causes severe neonatal meningitis and bacteremia, displays diverse lipopolysaccharide (LPS) structures. As a barrier of the bacterial cell, LPSs likely influenced C. sakazakii resistance to environment stresses; however, there are no research reports on this aspect, hindering the development of novel bactericidal strategies overcoming the pathogen’s resilience. In the present study, therefore, C. sakazakii BAA894 and two LPS mutants (ΔlpxM and ΔwaaC) were employed to investigate its influences. The ΔwaaC mutant showed lower resistance to acidic, alkali, oxidative, and osmotic stresses compared to the wild-type strain BAA894, and the ΔlpxM mutant exhibited lower desiccation resistance but higher osmotic resistance. To uncover potential reasons for these differences, comparative lipidomics was conducted. The results showed that compared to BAA894, both mutants showed drastic changes in lipid quantity, and many changed lipids were unsaturated. Additionally, eleven lipid classes exhibited significant variation in the relative content. In particular, the polyunsaturated TGs with double bonds at 5, 7, 12, and 14 displayed significant variation between the wild type and two mutants. Our study is the first to reveal that the changes in the LPS structure of C. sakazakii resulted in altered lipid profiles and intensities, which may be a critical biochemical basis for bacterial resistance to harsh stresses.
First Detection of a Novel Posavirus 2 Strain Identified from Pigs in China
Authors: Chen Li , Lu Haohao , Gao Xue , Zhou Han , Wang Jinghao , Zhang Zhidong , Chen Bin , Li Chun , Liang Luqi , Zhou Long , Zhang Yi
Published: November 2024

Porcine stool-associated RNA virus (Posavirus) is an unclassified virus with sequence similarity to viruses in the order of Picornaviridae. In China, lineage 1 Posavirus (Posavirus 1) has been circulating in the field since its initial emergence in 2014 however no other lineages have been reported. To investigate the genetic diversity of Posavirus in China, 1200 diarrheic samples were collected from pigs in China. Following high-throughput and Sanger sequencing, one complete genome sequence of a Posavirus (designated SC01) strain was obtained. The genome of SC01 strain was 10217 nucleotides in length and encoded a polyprotein of 3346 amino acids. Genome comparative analysis revealed that SC01 shared 85.6% nucleotide similarity to Posavirus 2 strains, but only 35.2–58.0% sequence identity with Posavirus 1 and 3–12 strains. Phylogenetic analysis showed that the SC01 was classified in Posavirus 2 and clustered into a separate branch with the American Posavirus 2 isolates, indicating that the SC01 is a Posavirus 2 strain. Notably, a novel 1-amino acid deletion was observed in polyprotein at amino acid position 147. This is the first report of the presence of Posavirus 2 in China, and the genomic data of SC01 provides insights into the genetic diversity and evolution of Posavirus in the region.
Use of a Novel Feeding System to Assess the Survival of a Very Stable Mammalian Virus, Porcine Parvovirus, Within Black Soldier Fly (Hermetia illucens) Larvae: A Comparison with Mealworm (Tenebrio molitor) Larvae
Authors: Lecocq Antoine , Alencar Anna Luiza Farias , Lazov Christina M. , Rajiuddin Sheikh M. , Bøtner Anette , Belsham Graham J.
Published: November 2024

Insect larvae production offers the potential for large-scale synthesis of high-quality protein that can be used as feed or food. However, currently, there are limitations on the source of substrates for the insect larvae to use. One concern is the potential survival of animal pathogens within insect larvae if their feed is contaminated. In this study, the survival of a very stable virus, porcine parvovirus (PPV), within mealworm (Tenebrio molitor) and black soldier fly (BSF) (Hermetia illucens) larvae has been analyzed after oral ingestion of the virus. PPV genomic DNA could be readily detected by PCR in both species of larvae up until 9 days post ingestion (DPI), the end of the study period. Furthermore, infection of susceptible PK15 cells by PPV from homogenized mealworm larvae could be detected until at least 3 DPI, using an immunoperoxidase staining method and, up until 9 DPI, with a more sensitive real time PCR assay. Thus, PPV can remain infectious within mealworm larvae during their main growth phase through to their harvesting. However, it may be considered that PPV is exceptional in this respect since it displays unusual stability, e.g., to heat.
Exploration of the Topical Nanoemulgel Bearing with Ferulic Acid and Essential Oil for Diabetic Wound Healing
Authors: Anuradha Urati , Bhavana Valamla , Chary Padakanti Sandeep , Kalia Nitin Pal , Mehra Neelesh Kumar
Published: November 2024

Aim: To investigate the anti-inflammatory, antioxidant, and diabetic wound healing properties of the novel topical formulation [Ferulic acid-loaded nanoemulgel (DLMGO-G)]. Methods: Ferulic acid nanoemulsion developed with lemongrass oil is investigated in diabetic wound healing. Further nanoemulsion is incorporated into 1% carbopol® 934 to obtain the DLMGO-G. Nanoemulsion was characterized for particle size, and polydispersity index (PDI) was obtained by Malvern Zetasizer (Zetasizer Nano ZS, Malvern, AL, USA), and morphology by TEM (JEM 1400, JOEL, Akishima, Japan). Furthermore, in vitro cell line and in vivo studies were carried out. Results: The developed nanoemulsion showed a globule size of 28.04 ± 0.23 nm and PDI of 0.07 ± 0.01. The morphology of nanoformulations by TEM confirmed the spherical and uniform nature. Further, the nanoformulation in in vitro cell line experiments revealed that the IC50 value was increased by 1.52 times compared to the drug solution. The treatment groups have shown that fibroblast morphologies were spindle-shaped, suggesting that nanoformulation was compatible with the cells and developed normally on nanoformulation. It also reduced ROS with improved internalization more than the control group. The in vitro wound healing model also revealed that nanoformulation had better wound healing activity. In the in vivo diabetic wound studies on male SD rats, the levels of inflammatory markers such as TNF-α, IL-6, IL-22, and IL-1β declined significantly when treated with DLMGO-G. IL-10 levels significantly increased compared to the diseased group, and MMP-9 levels were remarkably decreased compared to the diseased group. Furthermore, histopathological studies showed the regeneration and granulation of tissues. Conclusions: Thus, these findings indicate that FA-loaded nanoemulgel greatly accelerates the healing of wounds in diabetic rats.
Synthesis and Structure–Activity Relationship of Thiourea Derivatives Against Leishmania amazonensis
Authors: Viana Gil Mendes , Cunha-Junior Edézio Ferreira da , Assumpção Paloma Wetler Meireles Carreiros , Rezende Marianne Grilo , Emiliano Yago Sousa dos Santos , Soares Laiza Maria da Silva , Pereira Gabriel Rodrigues Coutinho , Rodrigues Carlos Rangel , Cabral Lucio Mendes , Torres-Santos Eduardo Caio
Published: November 2024

Background: Leishmaniasis, caused by Leishmania protozoa and transmitted by vectors, presents varied clinical manifestations based on parasite species and host immunity. The lack of effective vaccines or treatments has prompted research into new therapies, including thiourea derivatives, which have demonstrated antiprotozoal activities. Methods: We synthesized two series of N,N′-disubstituted thiourea derivatives through the reaction of isothiocyanates with amines. These compounds were evaluated in vitro against promastigote and amastigote forms of L. amazonensis, alongside cytotoxicity assessments on macrophages. In silico studies were conducted to analyze structure–activity relationships (SARs) and drug-likeness. Results: A total of fifty thiourea derivatives were synthesized and tested. Compound 3e from the first generation exhibited significant anti-leishmanial activity with an IC50 of 4.9 ± 1.2 µM and over 80-fold selectivity compared to that of miltefosine (IC50 = 7.5 ± 1.2 µM). The introduction of a piperazine ring in the second-generation thioureas enhanced potency and selectivity, with compound 5i achieving an IC50 of 1.8 ± 0.5 µM and a selectivity index of approximately 70. Pharmacokinetic predictions indicated favorable profiles for the active compounds. Conclusions: SAR and ADMET analyses identified compound 5i as the most promising candidate for further preclinical evaluation, suggesting that piperazine thiourea derivatives represent a novel class of anti-leishmanial agents.
Anti-Vascular Endothelial Growth Factor Combined with Ocular Steroid Therapy for Persistent Diabetic Macular Edema: A Systematic Review and Meta-Analysis
Authors: Ma Yunxi , Tao Yunhan , Yuan Mingzhu , Sun Xufang
Published: November 2024

Purpose: Our purpose was to appraise the efficacy and safety of intravitreous vascular endothelial growth factor inhibitor (anti-VEGF) therapy combined with steroids for persistent diabetic macular edema. Methods: A systematic review was conducted of the research evaluating the combination therapy of anti-VEGF and steroids for persistent diabetic macular edema compared to anti-VEGF alone. A meta-analysis was performed using a protocol registered in PROSPERO (CRD42023476333). Continuous and binary variables were extracted. Results were expressed as the mean difference (MD) and risk ratio (RR). Results: A total of 9 trials with 537 eyes were included. The MDs of improvement in best-corrected visual acuity (BCVA) at 1/2/3/6/9/12 months between the combined and monotherapy groups were 1.33 (95% CI [−1.31,3.96]), 3.03 (95% CI [0.01, 6.06]), −0.37 (95% CI [−4.74, 4.00]), −1.37 (95% CI [−4.65, 1.91]), 1.05 (95% CI [−3.68, 5.77]), and 1.70 (95% CI [−3.52, 6.93]). The MDs concerned with a central retinal thickness (CMT) decline in at 1/2/3/6/9/12 months between the two groups were −47.33, 95% CI [−94.35, −0.32]), −89.19 (95% CI [−114.38, −64.00]), −58.84 (95% CI [−96.93, −20.74]), −57.23 (95% CI [−102.62, −11.84]), −40.59 (95% CI [−80.59, −0.58]), and −38.89 (95% CI [−77.38, −0.40]), respectively. Furthermore, the combined group obtained higher relative risks of experiencing events with high intraocular pressure and progressed cataracts. Conclusions: Anti-VEGF combined with ocular steroids showed a significant advantage in improving the retinal anatomical structure compared to anti-VEGF monotherapy for persistent diabetic macular edema. However, as the treatment period extended, the combination treatment was no more effective than monotherapy after 2 months, with more severe side effects.
Evaluation of Dactylopius opuntiae Extract for Xanthine Oxidase Inhibition and Serum Uric Acid Reduction in a Hyperuricemic Mouse Model
Authors: Aragon-Martinez Othoniel H. , González-Chávez Marco M. , Galicia-Cruz Othir G. , Méndez-Gallegos Santiago de J. , Isiordia-Espinoza Mario A. , Martinez-Morales Flavio
Published: November 2024

Background/Objectives: Current urate-lowering therapies may cause serious side effects in patients. Thus, alternative treatments are needed to regulate uric acid (UA) levels in patients with hyperuricemia associated with kidney injury, and natural antioxidant sources have demonstrated utility in this field. For the first time, our study evaluated the effects of an extract of Dactylopius opuntiae insects on the levels of xanthine oxidase (XO) enzymes and synthetic free radicals in vitro and in vivo. Methods: Insects were bred and collected, and two different extracts (D1 and D2) were obtained. For both extracts, XO inhibition and radical scavenging assays were performed. Subsequently, serum purine levels and renal markers were quantified in male BALB/c mice who received a hyperuricemia induction using potassium oxonate, hypoxanthine, and gentamicin. Results: The D2 extract contained 18,037.7 µg/mL of carminic acid, inhibited 53.2% of XO activity at one concentration, and showed IC50 values of 18,207.8 and 5729.6 µg/mL against ABTS and DPPH radicals, respectively. D2 administration reduced serum UA and creatinine levels and prevented an increase in kidney weight and reduction in renal antioxidant capacity caused by hyperuricemia induction and allopurinol use in mice. Despite the satisfactory antioxidant results obtained in vitro, the D1 extract killed the animal models due to its citric acid content. Conclusions: The D2 insect extract can be used as an effective urate-lowering therapy when the increased level of serum uric acid is due to kidney damage.
Does Combined Treatment with Tranexamic Acid and Vancomycin Affect Human Chondrocytes In Vitro?
Authors: Wagenbrenner Mike , Heinz Tizian , Anderson Philip M. , Stratos Ioannis , Arnholdt Joerg , Mayer-Wagner Susanne , Horas Konstantin , Docheva Denitsa , Holzapfel Boris M. , Rudert Maximilian , Weißenberger Manuel
Published: November 2024

Background: The aim of our study was to examine the combined effects of tranexamic acid (TXA) and vancomycin powder (VP) on chondrocytes in vitro. Despite the use of TXA and VP being linked to a reduced risk of extensive postoperative blood loss and periprosthetic joint infections (PJIs) in TKA, the possible cytotoxic side effects on periarticular cell types remain unclear. Methods: Human chondrocytes were harvested from hyaline cartilage and expanded in monolayer culture before being simultaneously exposed to different concentrations of TXA and VP for varying exposure times. Cell viability and proliferation were assessed using an ATP assay and an Annexin 5 assay, respectively, while changes in the relative expression of chondrogenic marker genes were examined using semiquantitative RT-PCR. Results: The simultaneous exposure of chondrocytes to TXA and VP for more than 48 h led to a reduction in both cell viability and proliferation rates. When exposing chondrocytes to the lowest examined concentrations of both TXA (10 mg/mL) and VP (3 mg/mL), the observed effects were delayed until 96 h. However, our study found no dependencies of the observed effects on the concentrations tested. Further, we found no effects on the expression of chondrogenic marker genes. Conclusions: Consequently, limiting the exposure time of chondrocytes to TXA and VP in an in vitro setting to 24 h may be considered safe and could help to further improve the understanding of the safe use of substances in vivo. However, further in vitro research is required to develop a comprehensive understanding of the effects of both VP and TXA on important periarticular cell types in TKA, including chondrocytes, osteocytes, and tenocytes.
Phytochemical Profiling and Bioactivity Assessment of Teucrium capitatum L. Essential Oil and Extracts: Experimental and In Silico Insights
Authors: Tarik Redouane , Drioiche Aziz , El Amri Jalila , Ed-Dahmouny Mohamed , Shahat Abdelaaty Abdelaziz , Hadi Nadia , Aicha Mouradi , Nadia Handaq , El Makhoukhi Fadoua , El Ouali Lalami Abdelhakim , Elmoualij Noureddine , Bruno Eto , Lhoussain Hajji , Zair Touriya
Published: November 2024

Background: Teucrium capitatum L., a member of the Lamiaceae family, is widely used in traditional medicine for its therapeutic properties. This study aims to analyze the chemical composition of its essential oil and extracts, evaluate their antimicrobial and antioxidant activities, and investigate the interactions of their bioactive compounds with biological targets using in silico methods to better understand their mechanisms of action. Methods: Essential oil was extracted via hydrodistillation from leaves collected in Morocco, while phenolic compounds were obtained through Soxhlet and decoction extraction methods. Gas chromatography-mass spectrometry (GC-MS) was used for chemical profiling. Antimicrobial and antioxidant activities were assessed using standard methods, including DPPH, FRAP, and TAC assays. Molecular docking was conducted to explore interactions between major constituents and biological targets. Results: GC-MS analysis revealed significant bioactive components in the essential oil, such as β-pinene (24.5%), α-cadinol (17.02%), and shyobunol (12.13%). Extracts (hydro-ethanolic, hydro-methanolic, and aqueous via decoction) were rich in poliumoside (27.74%) and cirsimaritin (28.22%). The essential oil and extracts showed significant antimicrobial activity, particularly against Staphylococcus aureus, Escherichia coli, Candida albicans, and Aspergillus niger. Antioxidant assays confirmed strong activity. Molecular docking results supported strong interactions of major compounds with key biological targets. Conclusions: The high presence of phenolic and flavonoid compounds in Teucrium capitatum extracts contributes to their strong antimicrobial and antioxidant properties, supporting their potential for development as natural therapeutic agents.
Hemp Extract (Extractum Cannabis) in the Treatment of Gastrointestinal Distress and Dyspepsia: Historical Insights from Barcelona, Spain
Authors: Riboulet-Zemouli Kenzi , Allué Creus Josep
Published: November 2024

This study explores the trajectory of interest in and use of Extractum Cannabis (hemp extract, i.e., extract of Cannabis sativa L.) for the symptomatic treatment of minor gastrointestinal distress and dyspepsia in nineteenth- and early twentieth-century Barcelona (Catalonia, Spain) prior to 1939, through a review of primary sources. The objective of this paper is to present a historical pharmaceutical and applied review of the medical use of the hemp genus (Cannabis L.) prior to its prohibition, thereby contributing to its recognition as a medicinal product. The information provided demonstrates evidence of the medicinal use of cannabis within the historical context studied. The interactions between this legacy medical use and the contemporary body of pharmacological and toxicological knowledge (on hemp, its constituents, and the endocannabinoid system in gastrointestinal and stomach disorders) are discussed, providing new possible clinical perspectives. Within its limitations—including the scope, limited accessibility to, and varying quality of archives—this research contributes to a more granular understanding of the historical embeddedness of psychoactive hemp medicines in northeastern Spain, suggesting that medical and pharmaceutical traditions could play a role in informing contemporary approaches to “medical marijuana”.