bluuebunny/crossref_metadata_2025 huggingface dataset:
Appropriateness of Ketoanalogues of Amino Acids, Calcium Citrate, and Inulin Supplementation for CKD Management: A RAND/UCLA Consensus
Authors: Saavedra-Fuentes Nadia , Carmona-Montesinos Enrique , Castañeda-Hernández Gilberto , Campos Israel , Castillo-Salinas Juan Carlos , Castillo-Tapia Javier Alberto , Del Castillo-Loreto Karla Guadalupe , Falcón-Martínez Juan Carlos , Fuentes-García Raquel , García de León Guerrero Miguel Ángel , García-García Victor , Gómez-García Erika F. , González-Toledo Rafael , Jaime Angélica , Rely Kely , Lerma Claudia , Morales-Buenrostro Luis E. , Quilantan-Rodriguez Mateo , Rodriguez-Matías Adrián , Rojas-Rodriguez Felipe Octavio , Valdez-Ortiz Rafael , Wasung Michael , Ceron-Trujillo Berenice , Ramirez-Ramirez Edgar
Published: September 2024

Background: Current treatment for chronic kidney disease (CKD) focuses on improving manifestations and delaying progression. Nutritional approaches play a crucial role in CKD management, and various supplements have become available. Ketoanalogues of amino acids (KAs), calcium citrate, and inulin have been proposed as suitable supplements, yet their widespread use has been limited due to insufficient evidence. This study aimed to generate general guidance statements on the appropriateness of these supplements through a RAND/UCLA consensus process. Methods: A RAND/UCLA consensus panel was convened to evaluate the appropriateness of these supplements in different clinical scenarios. In this study, we present a subgroup analysis focusing on a panel of eleven clinical nephrologists from among the experts. Results: Supplementation of low-protein diets (LPDs) and very low-protein diets (VLPDs) with KA was considered appropriate to reduce manifestations and delay CKD outcomes, supplementation with calcium citrate is considered appropriate to reduce CKD manifestations, and supplementation with inulin is considered appropriate to delay CKD outcomes and manage comorbidities. Conclusions: Based on a combination of clinical experience and scientific evidence, the panel reached a consensus that KA supplementation of LPD and VLPD, calcium citrate, and inulin are appropriate in patients with CKD across various scenarios.
Validity of the Addiction-like Eating Behavior Scale among Patients with Compulsive Eating
Authors: Bourque Camille , Legendre Maxime , Iceta Sylvain , Bégin Catherine
Published: September 2024

Food addiction (FA) and binge eating disorder (BED) co-occur and share compulsive eating symptoms. When using an FA measure, it is important to evaluate its performance in a population presenting compulsive eating. The study aims to validate the Addiction-like Eating Behavior Scale (AEBS) among a clinical sample characterized by compulsive eating and overweight/obesity and to evaluate its incremental validity over the Yale Food Addiction Scale 2.0 (YFAS). Patients seeking help for compulsive eating (n = 220), between January 2020 and July 2023, completed online questionnaires, including FA, compulsive eating, and BMI evaluations. The factor structure, internal consistency, and convergent, divergent, and incremental validity were tested. The sample had a mean age of 44.4 years old (SD = 12.7) and a mean BMI of 38.2 (SD = 8.0). The two-factor structure provided a good fit for the data, with factor loadings from 0.55 to 0.82 (except for item 15) and the internal consistency was high (ω = 0.84–0.89). The AEBS was positively correlated with the YFAS (r = 0.66), binge eating (r = 0.67), grazing (r = 0.47), craving (r = 0.74), and BMI (r = 0.26), and negatively correlated with dietary restraint (r = −0.37), supporting good convergent and divergent validity. For each measure of compulsive eating, linear regression showed that the AEBS “appetite drive” subscale had a unique contribution over the YFAS. This study provided evidence that the AEBS is a valid measure among a clinical sample of patients with compulsive eating and overweight/obesity. However, questions remain as to whether the AEBS is a measure of FA or compulsive eating.
Optimal Pair Matching Combined with Machine Learning Predicts a Significant Reduction in Myocardial Infarction Risk in African Americans Following Omega-3 Fatty Acid Supplementation
Authors: Sun Shudong , Hara Aki , Johnstone Laurel , Hallmark Brian , Watkins Joseph C. , Thomson Cynthia A. , Schembre Susan M. , Sergeant Susan , Umans Jason G. , Yao Guang , Zhang Hao Helen , Chilton Floyd H.
Published: September 2024

Conflicting clinical trial results on omega-3 highly unsaturated fatty acids (n-3 HUFA) have prompted uncertainty about their cardioprotective effects. While the VITAL trial found no overall cardiovascular benefit from n-3 HUFA supplementation, its substantial African American (AfAm) enrollment provided a unique opportunity to explore racial differences in response to n-3 HUFA supplementation. The current observational study aimed to simulate randomized clinical trial (RCT) conditions by matching 3766 AfAm and 15,553 non-Hispanic White (NHW) individuals from the VITAL trial utilizing propensity score matching to address the limitations related to differences in confounding variables between the two groups. Within matched groups (3766 AfAm and 3766 NHW), n-3 HUFA supplementation’s impact on myocardial infarction (MI), stroke, and cardiovascular disease (CVD) mortality was assessed. A weighted decision tree analysis revealed belonging to the n-3 supplementation group as the most significant predictor of MI among AfAm but not NHW. Further logistic regression using the LASSO method and bootstrap estimation of standard errors indicated n-3 supplementation significantly lowered MI risk in AfAm (OR 0.17, 95% CI [0.048, 0.60]), with no such effect in NHW. This study underscores the critical need for future RCT to explore racial disparities in MI risk associated with n-3 HUFA supplementation and highlights potential causal differences between supplementation health outcomes in AfAm versus NHW populations.
Vitamin D Deficiency Does Not Affect Cognition and Neurogenesis in Adult C57Bl/6 Mice
Authors: Doumit Mark , El-Mallah Carla , El-Makkawi Alaa , Obeid Omar , Kobeissy Firas , Darwish Hala , Abou-Kheir Wassim
Published: September 2024

Vitamin D deficiency is a global problem. Vitamin D, the vitamin D receptor, and its enzymes are found throughout neuronal, ependymal, and glial cells in the brain and are implicated in certain processes and mechanisms in the brain. To investigate the processes affected by vitamin D deficiency in adults, we studied vitamin D deficient, control, and supplemented diets over 6 weeks in male and female C57Bl/6 mice. The effect of the vitamin D diets on proliferation in the neurogenic niches, changes in glial cells, as well as on memory, locomotion, and anxiety-like behavior, was investigated. Six weeks on a deficient diet was adequate time to reach deficiency. However, vitamin D deficiency and supplementation did not affect proliferation, neurogenesis, or astrocyte changes, and this was reflected on behavioral measures. Supplementation only affected microglia in the dentate gyrus of female mice. Indicating that vitamin D deficiency and supplementation do not affect these processes over a 6-week period.
Chios Mastic Gum: A Promising Phytotherapeutic for Cardiometabolic Health
Authors: Blomquist Sarah A. , Fernandez Maria Luz
Published: September 2024

Chios mastic gum (CMG) is a resin obtained from the Pistacia lentiscus var. Chia tree that grows in the Mediterranean. For millennia, it has been renowned for its medicinal properties, but recently, CMG has gained attention due to its pronounced anti-inflammatory and antioxidative properties and its use in oral health, inflammatory bowel disease, cancer, and risk factors related to cardiovascular and metabolic diseases. This narrative review seeks to briefly overview its bioactive constituents and examine and describe its potential as a cardiometabolic disease (CMD) phytotherapeutic. The results of clinical trials and in vivo, in vitro, and in silico studies provide accumulating evidence of the mechanisms underlying CMG’s impacts on lipid and glucose metabolism, cardiovascular and hepatic health, inflammation, oxidative stress, body composition, and microbiota. Despite the relatively limited studies with mixed results, they have provided the foundation to understand the strengths, weaknesses, and opportunities moving forward that may help to establish CMG and its bioactives as viable therapeutics for CMD.
Metabolic Characteristics of Gut Microbiota and Insomnia: Evidence from a Mendelian Randomization Analysis
Authors: Xie Fuquan , Feng Zhijun , Xu Beibei
Published: September 2024

Insomnia is a common sleep disorder that significantly impacts individuals’ sleep quality and daily life. Recent studies have suggested that gut microbiota may influence sleep through various metabolic pathways. This study aims to explore the causal relationships between the abundance of gut microbiota metabolic pathways and insomnia using Mendelian randomization (MR) analysis. This two-sample MR study used genetic data from the OpenGWAS database (205 gut bacterial pathway abundance) and the FinnGen database (insomnia-related data). We identified single nucleotide polymorphisms (SNPs) associated with gut bacterial pathway abundance as instrumental variables (IVs) and ensured their validity through stringent selection criteria and quality control measures. The primary analysis employed the inverse variance-weighted (IVW) method, supplemented by other MR methods, to estimate causal effects. The MR analysis revealed significant positive causal effects of specific carbohydrate, amino acid, and nucleotide metabolism pathways on insomnia. Key pathways, such as gluconeogenesis pathway (GLUCONEO.PWY) and TCA cycle VII acetate producers (PWY.7254), showed positive associations with insomnia (B > 0, p < 0.05). Conversely, pathways like hexitol fermentation to lactate, formate, ethanol and acetate pathway (P461.PWY) exhibited negative causal effects (B < 0, p < 0.05). Multivariable MR analysis confirmed the independent causal effects of these pathways (p < 0.05). Sensitivity analyses indicated no significant pleiotropy or heterogeneity, ensuring the robustness of the results. This study identifies specific gut microbiota metabolic pathways that play critical roles in the development of insomnia. These findings provide new insights into the biological mechanisms underlying insomnia and suggest potential targets for therapeutic interventions. Future research should further validate these causal relationships and explore how modulating gut microbiota or its metabolic products can effectively improve insomnia symptoms, leading to more personalized and precise treatment strategies.
Polyphenol-Rich Extract of Apocynum venetum L. Leaves Protects Human Retinal Pigment Epithelial Cells against High Glucose-Induced Damage through Polyol Pathway and Autophagy
Authors: Peng Jun , Abdulla Rahima , Liu Xiaoyan , He Fei , Xin Xuelei , Aisa Haji Akber
Published: September 2024

Diabetic retinopathy (DR) is a specific microvascular problem of diabetes, which is mainly caused by hyperglycemia and may lead to rapid vision loss. Dietary polyphenols have been reported to decrease the risk of DR. Apocynum venetum L. leaves are rich in polyphenolic compounds and are popular worldwide for their health benefits as a national tea drink. Building on previous findings of antioxidant activity and aldose reductase inhibition of A. venetum, this study investigated the chemical composition of polyphenol-rich extract of A. venetum leaves (AVL) and its protective mechanism on ARPE-19 cells in hyperglycemia. Ninety-three compounds were identified from AVL by LC-MS/MS, including sixty-eight flavonoids, twenty-one organic acids, and four coumarins. AVL regulated the polyol pathway by decreasing the expression of aldose reductase and the content of sorbitol, enhancing the Na+K+-ATPase activity, and weakening intracellular oxidative stress effectively; it also could regulate the expression of autophagy-related proteins via the AMPK/mTOR/ULK1 signaling pathway to maintain intracellular homeostasis. AVL could restore the polyol pathway, inhibit oxidative stress, and maintain intracellular autophagy to protect cellular morphology and improve DR. The study reveals the phytochemical composition and protective mechanisms of AVL against DR, which could be developed as a functional food and/or candidate pharmaceutical, aiming for retina protection in diabetic retinopathy.
No Money No Time Culinary Nutrition Website eHealth Challenge: A Pre-Post Evaluation of Impact on Diet Quality, Food Expenditure, and Engagement
Authors: Collins Rebecca A. , Ashton Lee M. , Burrows Tracy L. , Hutchesson Melinda , Adam Marc T. P. , Clarke Erin D. , Collins Clare E.
Published: September 2024

No Money No Time (NMNT) is a culinary nutrition website designed to optimize diet quality. The primary aim was to evaluate the impact of an online targeted nutrition challenge email campaign that encouraged engagement with NMNT and goal setting to improve diet quality and weekly food expenditure. A secondary aim was to assess NMNT engagement. Australian adults ≥18 years were recruited to the eHealth nutrition challenge delivered via weekly emails. Diet quality was assessed using the Healthy Eating Quiz (HEQ) diet quality tool. Engagement was assessed using email open and click-through rates. Intention-to-treat (ITT) analysis was conducted using mixed effects linear regression. Of 481 adults (49.7 ± 13.9 years, 84% female) who enrolled 79 (16%) completed the challenge. ITT results indicated statistically significant 6-week increases in diet quality score (+3.8 points p ≤ 0.001, d = 0.58) with sub-scale improvements in vegetables (+0.9 points, p = 0.01, d = 0.32), fruit (+1.2 points, p ≤ 0.001, d = 0.55), and dairy (+0.9 points, p ≤ 0.001, d = 0.58). There were significant post-challenge reductions in household spending on takeaway/snacks/coffee of AUD 8.9 per week (p = 0.01, d = 0.29), body weight reduction (−0.6 kg, p = 0.03, d = 0.26), and BMI (−0.2 kg/m2p = 0.02, d = 0.28). The email open rate remained constant at around 67% (56% to 75%), with an average click-through rate of 18% (7.1% to 37.9%). The eHealth nutrition challenge significantly improved diet quality while reducing BMI and money spent on discretionary foods. Strategies to scale the challenge should be tested as an innovative population strategy for improving diet quality, health indicators, and managing household food budgets.
Multi-Omics Profiles of Small Intestine Organoids in Reaction to Breast Milk and Different Infant Formula Preparations
Authors: Wang Xianli , Yang Shangzhi , Zheng Chengdong , Huang Chenxuan , Yao Haiyang , Guo Zimo , Wu Yilun , Wang Zening , Wu Zhenyang , Ge Ruihong , Cheng Wei , Yan Yuanyuan , Jiang Shilong , Sun Jianguo , Li Xiaoguang , Xie Qinggang , Wang Hui
Published: September 2024

Ensuring optimal infant nutrition is crucial for the health and development of children. Many infants aged 0–6 months are fed with infant formula rather than breast milk. Research on cancer cell lines and animal models is limited to examining the nutrition effects of formula and breast milk, as it does not comprehensively consider absorption, metabolism, and the health and social determinants of the infant and its physiology. Our study utilized small intestine organoids induced from human embryo stem cell (ESC) to compare the nutritional effects of breast milk from five donors during their postpartum lactation period of 1–6 months and three types of Stage 1 infant formulae from regular retail stores. Using transcriptomics and untargeted metabolomics approaches, we focused on the differences such as cell growth and development, cell junctions, and extracellular matrix. We also analyzed the roles of pathways including AMPK, Hippo, and Wnt, and identified key genes such as ALPI, SMAD3, TJP1, and WWTR1 for small intestine development. Through observational and in-vitro analysis, our study demonstrates ESC-derived organoids might be a promising model for exploring nutritional effects and underlying mechanisms.
Food Neophobia and Avoidant/Restrictive Food Intake among Adults and Related Factors
Authors: Białek-Dratwa Agnieszka , Staśkiewicz-Bartecka Wiktoria , Kiciak Agata , Wardyniec Aleksandra , Grajek Mateusz , Aktaç Şule , Çelik Zehra Margot , Sabuncular Güleren , İslamoğlu Ayşe Hümeyra , Kowalski Oskar
Published: September 2024

Avoidant/restrictive food intake disorder (ARFID) includes age-inappropriate feeding behaviors in eating patterns, including food neophobia, defined as refusal or reluctance to eat new or unknown foods. This study aimed to assess the prevalence of ARFID and food neophobia among adults and determine the related characteristics of these risks. The study used an anonymous survey questionnaire consisting of three parts as the research tool. The first part of the questionnaire was a metric and concerned socio-demographic data. The Food Neophobia Scale (FNS) and the Nine-Item Avoidance/Restrictive Food Disorder Screen Questionnaire (NIAS) were used to evaluate the eating disorders. The survey included 309 people (60.2% women, 39.8% men) aged 18–77 years. NIAS results indicated that 15.2% of the subjects showed food selectivity, and 11.0% had food anxiety. In the FNS assessment, 42.4% had a low risk of food neophobia, 38.2% a medium risk, and 19.4% a high risk. A higher risk of food neophobia correlated with higher NIAS scores, indicating a higher risk of ARFID (p = 0.00231). The NIAS score increased with the risk of food neophobia (p = 0.000). Respondents at low risk of neophobia were most likely to avoid several products (83.97%), while in the high-risk group, 56.67% did not want to eat a favorite food enriched with a new ingredient. A higher risk of neophobia was correlated with more food avoidance and adverse reactions to new foods (p = 0.000). A higher risk of food neophobia is strongly correlated with a higher risk of ARFID. Although demographics did not significantly impact NIAS results, some trends were noted, such as higher scores among older and underweight people. Those with a higher risk of food neophobia show more food avoidance and a greater reluctance to experiment with new ingredients. Public education should emphasize that eating disorders affect both sexes equally, with tailored interventions for high-risk groups such as the elderly, rural populations, and those with lower education. Health policies should promote access to nutrition education, psychological support, and diverse food options, while further research is needed to improve targeted interventions.
Comprehensive Analysis of Berberis aristata DC. Bark Extracts: In Vitro and In Silico Evaluation of Bioaccessibility and Safety
Authors: Rigillo Giovanna , Cappellucci Giorgio , Baini Giulia , Vaccaro Federica , Miraldi Elisabetta , Pani Luca , Tascedda Fabio , Bruni Renato , Biagi Marco
Published: September 2024

Berberine (BER) is an alkaloid found, together with other protoberberinoids (PROTBERs), in several species used in medicines and food supplements. While some herbal preparations containing BER and PROTBERs, such as Berberis aristata DC. bark extracts, have shown promising potential for human health, their safety has not been fully assessed. Recently, the EFSA issued a call for data to deepen the pharmacokinetic and pharmacodynamic understanding of products containing BER and PROTBERs and to comprehensively assess their safety, especially when used in food supplements. In this context, new data were collected in this work by assessing: (i) the phytochemical profile of 16 different commercial B. aristata dry extracts, which are among the most widely used preparations containing BER and PROTBERs in Europe; (ii) the In Vitro and In Silico investigation of the pharmacokinetic properties of BER and PROTBERs; (iii) the In Vitro cytotoxicity of selected extracts in different human cell lines, including tests on hepatic cells in the presence of CYP450 substrates; (iv) the effects of the extracts on cancer cell migration; and (v) the In Vitro molecular effects of extracts in non-cancer human cells. Results showed that commercial B. aristata extracts contain BER as the main constituent, with jatrorrhizine as main secondary PROTBER. BER and jatrorrhizine were found to have a good bioaccessibility rate, but they interact with P-gp. B. aristata extracts showed limited cytotoxicity and minimal interaction with CYP450 substrates. Furthermore, tested extracts demonstrated inhibition of cancer cell migration and were devoid of any pro-tumoral effects in normal cells. Overall, our work provides a valuable overview to better elucidate important concerns regarding botanicals containing BER and PROTBERs.
Gammaherpesvirus Infection Stimulates Lung Tumor-Promoting Inflammation
Authors: Mukhopadhyay Sudurika S. , Swan Kenneth F. , Pridjian Gabriella , Kolls Jay K. , Zhuang Yan , Yin Qinyan , Lasky Joseph A. , Flemington Erik , Morris Cindy A. , Lin Zhen , Morris Gilbert F.
Published: September 2024

Lung tumor-promoting environmental exposures and γherpesvirus infections are associated with Type 17 inflammation. To test the effect of γherpesvirus infection in promoting lung tumorigenesis, we infected mutant K-Ras-expressing (K-RasLA1) mice with the murine γherpesvirus MHV68 via oropharyngeal aspiration. After 7 weeks, the infected mice displayed a more than 2-fold increase in lung tumors relative to their K-RasLA1 uninfected littermates. Assessment of cytokines in the lung revealed that expression of Type 17 cytokines (Il-6, Cxcl1, Csf3) peaked at day 7 post-infection. These observations correlated with the post-infection appearance of known immune mediators of tumor promotion via IL-17A in the lungs of tumor-bearing mice. Surprisingly, Cd84, an immune cell marker mRNA, did not increase in MHV68-infected wild-type mice lacking lung tumors. Csf3 and Cxcl1 protein levels increased more in the lungs of infected K-RasLA1 mice relative to infected wild-type littermates. Flow cytometric and transcriptomic analyses indicated that the infected K-RasLA1 mice had increased Ly6Gdim/Ly6Chi immune cells in the lung relative to levels seen in uninfected control K-RasLA1 mice. Selective methylation of adenosines (m6A modification) in immune-cell-enriched mRNAs appeared to correlate with inflammatory infiltrates in the lung. These observations implicate γherpesvirus infection in lung tumor promotion and selective accumulation of immune cells in the lung that appears to be associated with m6A modification of mRNAs in those cells.
Bacteraemia Associated with Bilophila wadsworthia: A Rare Case Presentation from Hungary
Authors: Kovács Renátó , Árokszállási Tamás , Bozó Aliz , Jakab Ágnes , Bábel Krisztina Szonja , Héja Máté , Kovács Kitti Bernadett , Balázs Bence , Vitális Eszter , Majoros László , Tóth Zoltán
Published: September 2024

Bilophila wadsworthia is a Gram-negative anaerobic bacterium. In current study, it was identified in the bloodstream of a 69-year-old man admitted to the Neurology Clinic at the University of Debrecen, Clinical Centre, Hungary, for internal carotid artery stent implantation. Bacteraemia caused by B. wadsworthia is extremely rare, with very few cases reported worldwide. This case is notable because it is the first instance in which whole-genome sequencing of B. wadsworthia derived from blood was performed. Moreover, the sequence data have been deposited in a public database.
Harnessing Trichoderma spp.: A Promising Approach to Control Apple Scab Disease
Authors: Gouit Safae , Chair Ismahane , Belabess Zineb , Legrifi Ikram , Goura Khadija , Tahiri Abdessalem , Lazraq Abderrahim , Lahlali Rachid
Published: September 2024

Apple scab, caused by the pathogenic fungus Venturia inaequalis, can result in significant economic losses. The frequent use of fungicidal products has led to the emergence of isolates resistant to commonly used active substances. Therefore, biological control offers a sustainable alternative for managing apple scab. In this study, eight Trichoderma isolates were evaluated against five different isolates of V. inaequalis isolated from the Fes-Meknes region. The biocontrol potential of these Trichoderma isolates had previously been demonstrated against other pathogens. The results indicated that the inhibition rate of mycelial growth of V. inaequalis obtained with Trichoderma spp. isolates ranged from 50% to 81%, with significant differences observed among the pathogenic isolates after 5 and 12 days of incubation. In addition, the in vitro tests with Trichoderma cell-free filtrates showed inhibition rates ranging from 2% to 79%, while inhibition rates ranged from 5% to 78% for volatile compound tests. Interestingly, the inhibition of spore germination and elongation was approximately 40–50%, suggesting the involvement of antifungal metabolites in their biocontrol activities. The in vivo bioassay on detached apple leaves confirmed the biocontrol potential of these Trichoderma isolates and demonstrated their ability to preventively control apple scab disease. However, their efficacies were still lower than those of the fungicidal product difenoconazole. These findings could contribute to the development of an effective biofungicide based on these Trichoderma isolates for reliable and efficient apple scab control.
Serological Assessment of Lyme borreliosis in Bulgaria: A Nationwide Study
Authors: Ngoc Kim , Trifonova Iva , Gladnishka Teodora , Taseva Evgenia , Panayotova Elitsa , Vladimirova Iva , Ivanova Vladislava , Kuteva Eleonora , Christova Iva
Published: September 2024

Lyme borreliosis (LB), a tick-borne infection caused by bacteria in the Borrelia burgdorferi sensu lato complex, is increasingly prevalent on the Balkan Peninsula, including Bulgaria, where it is the most common tick-borne disease. This study aimed to assess the seroprevalence of LB across Bulgaria by analyzing 1892 serum samples for specific IgG antibodies using a two-tier testing protocol involving an ELISA and immunoblot methods. The results revealed an overall seroprevalence rate of 5.4%, with significant variation based on age, sex, and residence. Seroprevalence increased with age, peaking at 8.4% in individuals over 65 years. Males had a seroprevalence of 8.4% compared to 3.3% in females, and rural residents showed higher seroprevalence (10.2%) compared to urban residents (4.4%). Regional analysis indicated that seroprevalence ranged from 0.0% to 20.0%, with higher rates in northern provinces such as Gabrovo (18.9%) and Targovishte (20.0%). This study highlights the importance of two-step testing protocols for accurate diagnosis and underscores the need for increased awareness and further research to enhance public health measures and the management of LB in Bulgaria.
Evaluation of the Pharmaceutical Activities of Chuanxiong, a Key Medicinal Material in Traditional Chinese Medicine
Authors: Huang Shiwei , Chen Jiamei , Liu Xiaohua , Xing Chunxin , Zhao Lu , Chan Kelvin , Lu Guanghua
Published: September 2024

Szechwan lovage rhizome (SLR, the rhizome of Ligusticum chuanxiong Hort., Chuanxiong in Chinese transliteration) is one Chinese materia medica (CMM) commonly used to activate blood circulation and remove blood stasis. SLR is applicable to most blood stasis syndromes. It has significant clinical efficacy in relation to human diseases of the cardiocerebrovascular system, nervous system, respiratory system, digestive system, urinary system, etc. Apart from China, SLR is also used in Singapore, Malaysia, the European Union, and the United States of America. However, the current chemical markers in pharmacopeia or monography for the quality assessment of SLR are not well characterized or specifically characterized, nor do they fully reflect the medicinal efficacy of SLR, resulting in the quality of SLR not being effectively controlled. CMM can only have medicinal efficacy when they are applied in vivo to an organism. The intensity of their pharmaceutical activities can more directly represent the quality of CMM. Therefore, the chemical constituents and pharmacological actions of SLR are reviewed in this paper. In order to demonstrate the medicinal efficacy of SLR in promoting blood circulation and removing blood stasis, bioassay methods are put forward to evaluate the pharmaceutical activities of SLR to improve hemorheology, hemodynamics, and vascular microcirculation, as well as its anti-platelet aggregation and anticoagulation properties. Through comprehensive analyses of these pharmaceutical properties, the quality and therapeutic value of SLR are ascertained.
Neuroregeneration Improved by Sodium-D,L-Beta-Hydroxybutyrate in Primary Neuronal Cultures
Authors: Ari Csilla , D’Agostino Dominic P. , Cha Byeong J.
Published: September 2024

Ketone bodies are considered alternative fuels for the brain when glucose availability is limited. To determine the neuroregenerative potential of D,L-sodium-beta-hydroxybutyrate (D/L-BHB), Sprague Dawley rat primary cortical neurons were exposed to simulated central nervous system injury using a scratch assay. The neuronal cell migration, cell density and degree of regeneration in the damaged areas (gaps) in the absence (control) and presence of BHB (2 mM) were documented with automated live-cell imaging by the CytoSMART system over 24 h, which was followed by immunocytochemistry, labeling synapsin-I and β3-tubulin. The cell density was significantly higher in the gaps with BHB treatment after 24 h compared to the control. In the control, only 1.5% of the measured gap areas became narrower over 24 h, while in the BHB-treated samples 49.23% of the measured gap areas became narrower over 24 h. In the control, the gap expanded by 63.81% post-injury, while the gap size decreased by 10.83% in response to BHB treatment, compared to the baseline. The cell density increased by 97.27% and the gap size was reduced by 74.64% in response to BHB, compared to the control. The distance travelled and velocity of migrating cells were significantly higher with BHB treatment, while more synapsin-I and β3-tubulin were found in the BHB-treated samples after 24 h, compared to the control. The results demonstrate that D/L-BHB enhanced neuronal migration and molecular processes associated with neural regeneration and axonogenesis. These results may have clinical therapeutic applications in the future for nervous system injuries, such as for stroke, concussion and TBI patients.
Application of Hydrophilic Polymers to the Preparation of Prolonged-Release Minitablets with Bromhexine Hydrochloride and Bisoprolol Fumarate
Authors: Grzejdziak Agata , Brniak Witold , Lengier Olaf , Żarek Justyna Anna , Hliabovich Dziyana , Mendyk Aleksander
Published: September 2024

Minitablets have been extensively studied in recent years as a convenient pediatric form because they allow successful administration even in very young children. Their advantages include easy dose adjustment by multiplication of single units as well as the possibility of drug release modification by coating or forming matrix systems. The aim of this study was to demonstrate the possibility of the formulation of prolonged-release minitablets with bromhexine hydrochloride (BHX) and bisoprolol fumarate (BFM) dedicated to pediatric patients. Minitablets with 3 mm diameter and 15 mg mass, containing 1 mg of active substance in 1 unit, were prepared by direct compression with hydroxypropyl methylcellulose (HPMC) of different grades, methylcellulose, sodium alginate, or polyvinyl alcohol (PVA) as a sustained-release polymer. Different amounts of polymers and different compression forces were evaluated. Analysis of minitablets included their uniformity, hardness, and dissolution tests. The kinetics of drug substance release were analyzed with dedicated software. The prepared minitablets met the pharmacopeial requirements with respect to the uniformity of mass and content. The compressibility of BFM was significantly better than that of BHX, yet all minitablets had good mechanical properties. Dissolution studies showed a strong relationship between the type of polymer and its amount in the mass of a tablet and the dissolution rate. Prolonged release of up to 8 h was achieved when HPMC of 4000 cP viscosity was used in the amount of 30% to 80%. Sodium alginate in the amount of 50% was also effective in prolonging dissolution, but PVA was much less effective. Studies on the release kinetics showed that dissolution from prolonged-release minitablets with BHX fit the best to Hopfenberg or Hixson–Crowell models, while in the case of BFM, the best fit was found for Hopfenberg or Korsmeyer–Peppas models.
Cationic Curcumin Nanocrystals Liposomes for Improved Oral Bioavailability: Formulation Development, Optimization, In Vitro and In Vivo Evaluation
Authors: Cheng Xiang , Han Xiaoran , Si Jia , Dong Cong , Ji Zhongjuan , Zhao Shicong , Wu Xiangting , Li Haiyan , Jin Xiangqun
Published: September 2024

Curcumin, a naturally occurring poorly water-soluble polyphenol with a broad spectrum, is a typical BCS IV drug. The objective of this study was to develop curcumin nanocrystals liposomes with the aim of improving bioavailability. In this study, we prepared cationic curcumin nanocrystals with a particle size of only 29.42 nm; such a phenomenal range of particle sizes is very rare. Moreover, we summarized and evaluated the parameters of the nanocrystal preparation process, including methods, formulations, etc., and the rules we concluded can be generalized to other nanocrystal preparation processes. To counteract the instability of the nanocrystals in the digestive tract, cationic curcumin nanocrystals were loaded into negatively charged liposomes through gravitational force between different charges. Unexpectedly, chitosan oligosaccharide was found to promote the self-assembly process of curcumin nanocrystal liposomes. In vitro and in vivo experiments demonstrated that chitosan-modified curcumin nanocrystal liposomes exhibited enhanced resistance to enzyme barriers, mucus barriers, and cellular barriers, resulting in a 5.4-fold increase in bioavailability compared to crude powder formulations. It can be concluded that cationic nanocrystals liposomes represent an appropriate novel strategy for improving the dissolution rate and bioavailability of poorly soluble natural products such as curcumin.
In Silico Approach to Model Heat Distribution of Magnetic Hyperthermia in the Tumoral and Healthy Vascular Network Using Tumor-on-a-Chip to Evaluate Effective Therapy
Authors: Munoz Juan Matheus , Pileggi Giovana Fontanella , Nucci Mariana Penteado , Alves Arielly da Hora , Pedrini Flavia , Valle Nicole Mastandrea Ennes do , Mamani Javier Bustamante , Oliveira Fernando Anselmo de , Lopes Alexandre Tavares , Carreño Marcelo Nelson Páez , Gamarra Lionel Fernel
Published: September 2024

Glioblastoma multiforme (GBM) is the most severe form of brain cancer in adults, characterized by its complex vascular network that contributes to resistance to conventional therapies. Thermal therapies, such as magnetic hyperthermia (MHT), emerge as promising alternatives, using heat to selectively target tumor cells while minimizing damage to healthy tissues. The organ-on-a-chip can replicate this complex vascular network of GBM, allowing for detailed investigations of heat dissipation in MHT, while computational simulations refine treatment parameters. In this in silico study, tumor-on-a-chip models were used to optimize MHT therapy by comparing heat dissipation in normal and abnormal vascular networks, considering geometries, flow rates, and concentrations of magnetic nanoparticles (MNPs). In the high vascular complexity model, the maximum velocity was 19 times lower than in the normal vasculature model and 4 times lower than in the low-complexity tumor model, highlighting the influence of vascular complexity on velocity and temperature distribution. The MHT simulation showed greater heat intensity in the central region, with a flow rate of 1 µL/min and 0.5 mg/mL of MNPs being the best conditions to achieve the therapeutic temperature. The complex vasculature model had the lowest heat dissipation, reaching 44.15 °C, compared to 42.01 °C in the low-complexity model and 37.80 °C in the normal model. These results show that greater vascular complexity improves heat retention, making it essential to consider this heterogeneity to optimize MHT treatment. Therefore, for an efficient MHT process, it is necessary to simulate ideal blood flow and MNP conditions to ensure heat retention at the tumor site, considering its irregular vascularization and heat dissipation for effective destruction.
Lipid-Based Nanocarriers: Bridging Diagnosis and Cancer Therapy
Authors: Giordano Alessandra , Provenza Anna Chiara , Reverchon Giorgio , Baldino Lucia , Reverchon Ernesto
Published: September 2024

Theranostics is a growing field that matches diagnostics and therapeutics. In this approach, drugs and techniques are uniquely coupled to diagnose and treat medical conditions synergically or sequentially. By integrating diagnostic and treatment functions in a single platform, the aim of theranostics is to improve precision medicine by tailoring treatments based on real-time information. In this context, lipid-based nanocarriers have attracted great scientific attention due to their biodegradability, biocompatibility, and targeting capabilities. The present review highlights the latest research advances in the field of lipid-based nanocarriers for cancer theranostics, exploring several ways of improving in vivo performance and addressing associated challenges. These nanocarriers have significant potential to create new perspectives in the field of nanomedicine and offer promise for a significant step towards more personalized and precise medicine, reducing side effects and improving clinical outcomes for patients. This review also presents the actual barriers to and the possible challenges in the use of nanoparticles in the theranostic field, such as regulatory hurdles, high costs, and technological integration. Addressing these issues through a multidisciplinary and collaborative approach among institutions could be essential for advancing lipid nanocarriers in the theranostic field. Such collaborations can leverage diverse expertise and resources, fostering innovation and overcoming the complex challenges associated with clinical translation. This approach will be crucial for realizing the full potential of lipid-based nanocarriers in precision medicine.
Landscape, Human Disturbance, and Climate Factors Drive the Species Richness of Alien Invasive Plants on Subtropical Islands
Authors: Xie Yanqiu , Huang Hui , Xie Xinran , Ou Jingyao , Chen Zhen , Lu Xiaoxue , Kong Deyi , Nong Liebo , Lin Manni , Qian Zhijun , Mao Yue , Chen Ying , Wang Yingxue , Chen Zujian , Deng Chuanyuan
Published: September 2024

Invasive alien plants (IAPs) pose a significant threat to island biodiversity and severely impact ecosystems. Understanding the species–area relationship and environmental determinants of growth forms for IAP species on subtropical islands is crucial for establishing an IAP’s early warning mechanism, enhancing island ecological management, and protecting the ecosystems of Fujian and other subtropical islands. The study identified significant species–area relationships for IAPs and different life-form plants (trees, shrubs, and herbs), with slopes of 0.27, 0.16, 0.15, and 0.24, respectively. The small island effect does not apply to all species. Isolation has little effect on species richness, and the IAPs on Fujian islands do not conform to the isolation effect in island biogeography. Landscape factors are the main determinants of IAPs and different life-form species richness, with area, shape index, and perimeter–area ratio being the three primary landscape factors. These environmental factors are closely related to habitat heterogeneity. Besides landscape factors, different life forms respond differently to environmental factors. Climate drives the species richness distribution of shrubs and herbs, while trees are mainly influenced by human activities. Overall, landscape, human disturbance, and climate jointly drive the distribution of IAPs, with landscape factors being the most significant.
A Comprehensive Review of Climate Change and Plant Diseases in Brazil
Authors: Angelotti Francislene , Hamada Emília , Bettiol Wagner
Published: September 2024

Analyzing the impacts of climate change on phytosanitary problems in Brazil is crucial due to the country’s special role in global food security as one of the largest producers of essential commodities. This review focuses on the effects of climate change on plant diseases and discusses its main challenges in light of Brazil’s diverse agricultural landscape. To assess the risk of diseases caused by fungi, bacteria, viruses, oomycetes, nematodes, and spiroplasms, we surveyed 304 pathosystems across 32 crops of economic importance from 2005 to 2022. Results show that diseases caused by fungi account for 79% of the pathosystems evaluated. Predicting the occurrence of diseases in a changing climate is a complex challenge, and the continuity of this work is strategic for Brazil’s agricultural defense. The future risk scenarios analyzed here aim to help guide disease mitigation for cropping systems. Despite substantial progress and ongoing efforts, further research will be needed to effectively prevent economic and environmental damage.
Exploring Metabolomics to Innovate Management Approaches for Fall Armyworm (Spodoptera frugiperda [J.E. Smith]) Infestation in Maize (Zea mays L.)
Authors: Desika Jayasaravanan , Yogendra Kalenahalli , Hepziba Sundararajan Juliet , Patne Nagesh , Vivek Bindiganavile Sampath , Ravikesavan Rajasekaran , Nair Sudha Krishnan , Jaba Jagdish , Razak Thurapmohideen Abdul , Srinivasan Subbiah , Shettigar Nivedita
Published: September 2024

The Fall armyworm (FAW), Spodoptera frugiperda (J. E. Smith), is a highly destructive lepidopteran pest known for its extensive feeding on maize (Zea mays L.) and other crops, resulting in a substantial reduction in crop yields. Understanding the metabolic response of maize to FAW infestation is essential for effective pest management and crop protection. Metabolomics, a powerful analytical tool, provides insights into the dynamic changes in maize’s metabolic profile in response to FAW infestation. This review synthesizes recent advancements in metabolomics research focused on elucidating maize’s metabolic responses to FAW and other lepidopteran pests. It discusses the methodologies used in metabolomics studies and highlights significant findings related to the identification of specific metabolites involved in FAW defense mechanisms. Additionally, it explores the roles of various metabolites, including phytohormones, secondary metabolites, and signaling molecules, in mediating plant–FAW interactions. The review also examines potential applications of metabolomics data in developing innovative strategies for integrated pest management and breeding maize cultivars resistant to FAW by identifying key metabolites and associated metabolic pathways involved in plant–FAW interactions. To ensure global food security and maximize the potential of using metabolomics in enhancing maize resistance to FAW infestation, further research integrating metabolomics with other omics techniques and field studies is necessary.
Exploring Ethnobotany in the Catalan Linguistic Area: Traditional Plant-Based Knowledge for Addressing Gastrointestinal, Metabolic, and Nutritional Disorders
Authors: Cáceres Fuencisla , Vallès Joan , Gras Airy
Published: September 2024

Ethnobotanical research in the Catalan linguistic area (CLA) is crucial due to the persistence of traditional medicinal plant knowledge. Gastrointestinal, metabolic, and nutritional disorders are major global health issues requiring effective treatments. This study aimed to analyze plants used for these disorders in the CLA, compare the findings with phytotherapy literature, and examine correlations between plant use in humans and animals. Data were sourced from the database of the research group of Catalan ethnobotany at the University of Barcelona and the Botanic Institute of Barcelona, representing a collection of ethnobotanical studies. A total of 630 plant taxa were examined, with 15,252 use reports (UR) provided by 2301 informants. Gastrointestinal disorders were the focus, comprising 94.24% of the UR. The high informant consensus factor (0.96) indicated strong reliability of the results. The most often reported species were Matricaria recutita (5.97%), Thymus vulgaris (5.12%), and Lippia triphylla (4.90%). Lamiaceae (19.86%), Asteraceae (18.78%), and Rosaceae (5.55%) were the top botanical families. The main uses were digestive (17.62%), intestinal anti-inflammatory (15.68%), and antidiarrheal (8.91%). The main part of the plant used was the aerial part (33.22%). Tisane (69.25%) was the most cited pharmaceutical form. Traditional uses were confirmed by pharmacological literature in 57.59% of cases. This work highlights the potential of medicinal plants for treating gastrointestinal, metabolic, and nutritional disorders in the CLA. Further research is possible in other territories, as well as in the phytochemical and medicinal aspects of the plants recorded.
Application of Magnetized Ionized Water and Bacillus subtilis Improved Saline Soil Quality and Cotton Productivity
Authors: Jiang Zhanbo , Wang Quanjiu , Ning Songrui , Lin Shudong , Hu Xiaoqin , Song Zhaoxin
Published: September 2024

Soil salinization, a significant global challenge, threatens sustainable development. This study explores the potential of magnetized ionized water irrigation and Bacillus subtilis application to mitigate this issue. The former method is hypothesized to enhance soil salt leaching, while the latter is expected to improve soil nutrient availability, thereby increasing microbial diversity. To address the unclear impact of these interventions on soil quality and cotton productivity, this study employs four different experimental methods: magnetized ionized water irrigation (M), application of 45 kg ha−1 B. subtilis (B), a combination of 45 kg ha−1 B. subtilis with magnetized ionized water irrigation (MB), and a control treatment with no intervention (CK). This study aims to clarify the effects of these treatments on soil bulk density (BD), field capacity (FC), salinity and alkalinity, nutrient content, microbial activity, and cotton crop yield and quality. Additionally, it aims to evaluate the efficacy of these methods in improving saline soil conditions by developing a soil quality index. The results showed that using magnetized ionized water for irrigation and applying B. subtilis, either alone or together, can effectively lower soil pH and salt levels, enhance microbial diversity and abundance, and improve the yield and quality of cotton. Notably, B. subtilis application significantly decreased BD and enhanced FC and nutrient content (p < 0.05). A correlation was found where soil nutrient content decreased as pH and salt content increased. Furthermore, a strong correlation was observed between the major soil bacteria and fungi with BD, FC, and salt content. Comparatively, M, B, and MB significantly boosted (p < 0.01) the soil quality index by 0.21, 0.52, and 0.69 units, respectively, and increased (p < 0.05) cotton yield by 5.7%, 14.8%, and 20.1% compared to CK. Therefore, this research offers eco-friendly and efficient methods to enhance cotton production capacity in saline soil.