bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence and Risk Factors of Osteoporosis: A Cross-Sectional Study in a Tertiary Center
Authors: Özmen Samican , Kurt Sefa , Timur Hikmet Tunç , Yavuz Onur , Kula Hakan , Demir Ayşegül Yılmaz , Balcı Ali
Published: December 2024

Background and Objectives: Osteoporosis is a common disease of the skeletal system that increases the risk of fracture. The prevalence of osteoporosis has been increasing as the aging population increases, affecting more than 200 million people worldwide. This study aimed to shed light on the clinical impact of osteoporosis on women’s health and quality of life by evaluating the prevalence and risk factors for this disease among postmenopausal women, using a 10-year dataset from a tertiary center. Materials and Methods: This retrospective cohort study was conducted at Dokuz Eylül University, Department of Obstetrics and Gynecology, between 2010 and 2022. A total of 3289 postmenopausal women aged 50–60 years who were undergoing routine gynecological checkups were included in the study. Patients with a prior diagnosis, a history of medical conditions, or who were taking medications affecting bone mineral density (BMD) were excluded. Data on demographics, smoking status, diabetes status, body mass index (BMI), parity, and fracture history were collected. BMD scores were classified as normal, osteopenia, or osteoporosis. Results: The prevalence of osteoporosis was 10.4%. The median age of the patients was 56.0 years. Smoking, diabetes, and a history of bone fractures were found to significantly increase the risk of osteoporosis. BMI was found to have a protective effect against osteoporosis. According to multivariate analysis, the risk of osteoporosis increased by 2.46 times in patients who smoke, 3.78 times in patients with diabetes, and 6.23 times in patients with a history of fractures. Conclusions: Awareness of modifiable risk factors such as smoking is crucial for preventing osteoporosis-related complications. Diabetes, even when it is not complicated, increases the risk of osteoporosis. Physical exercise, calcium, and vitamin D intake are important, especially during young adulthood, as they are the primary contributors to peak bone mass. Because neck fractures are more common in patients with osteopenia, early diagnosis and routine screening can mitigate future complications.
Stem Cells Within Three-Dimensional-Printed Scaffolds Facilitate Airway Mucosa and Bone Regeneration and Reconstruction of Maxillary Defects in Rabbits
Authors: Lim Mi Hyun , Jeon Jung Ho , Park Sun Hwa , Yun Byeong Gon , Kim Seok-Won , Cho Dong-Woo , Lee Jeong Hak , Kim Do Hyun , Kim Sung Won
Published: December 2024

Background and Objectives: Current craniofacial reconstruction surgical methods have limitations because they involve facial deformation. The craniofacial region includes many areas where the mucosa, exposed to air, is closely adjacent to bone, with the maxilla being a prominent example of this structure. Therefore, this study explored whether human neural-crest-derived stem cells (hNTSCs) aid bone and airway mucosal regeneration during craniofacial reconstruction using a rabbit model. Materials and Methods: hNTSCs were induced to differentiate into either mucosal epithelial or osteogenic cells in vitro. hNTSCs were seeded into polycaprolactone scaffold (three-dimensionally printed) that were implanted into rabbits with maxillary defects. Four weeks later, tissue regeneration was analyzed via histological evaluation and immunofluorescence staining. Results: In vitro, hNTSCs differentiated into both mucosal epithelial and osteogenic cells. hNTSC differentiation into respiratory epithelial cells was confirmed by Alcian Blue staining, cilia in SEM, and increased expression levels of FOXJ1 and E-cadherin through quantitative RT-PCR. hNTSC differentiation into bone was confirmed by Alizarin Red staining, increased mRNA expression levels of BMP2 (6.1-fold) and RUNX2 (2.3-fold) in the hNTSC group compared to the control. Four weeks post-transplantation, the rabbit maxilla was harvested, and H&E, SEM, and immunohistofluorescence staining were performed. H&E staining and SEM showed that new tissue and cilia around the maxillary defect were more prominent in the hNTSC group. Also, the hNTSCs group showed positive immunohistofluorescence staining for acetylated α-tubulin and cytokerin-5 compared to the control group. Conclusions: hNTSCs combined with PCL scaffold enhanced the regeneration of mucosal tissue and bone in vitro and promoted mucosal tissue regeneration in the in vivo rabbit model.
Numerical Simulations of Stress Intensity Factors and Fatigue Life in L-Shaped Sheet Profiles
Authors: Dömling Ferdinand , Paysan Florian , Breitbarth Eric
Published: December 2024

The assessment of fatigue cracks is an elementary part of the design process of lightweight structures subject to operational loads. Although angled sheets are standard components in forming technology, fatigue crack growth in geometries like C- and L-sections has been little-studied and is mostly limited to crack growth before the transition through the corner. In this study, fatigue crack propagation is simulated to explore the influence of sheet thickness, corner angle and corner radius on the fatigue life in an L-section. The stress intensity factor (SIF) is derived as the driving force of crack growth over the full crack path. Special attention is paid to the evolution of the SIF in the radius sub-section and its implications on the fatigue life. The results show that the SIF in an angled sheet for given loading conditions and crack lengths cannot be readily approximated by the SIF in an equivalent straightened sheet. The bending angle and radius lead to crack growth retardation or acceleration effects. These findings are important for the design and optimization of forming geometries with regard to fatigue crack growth.
Analysis of Immunosuppression and Antioxidant Damage in Diploid and Triploid Crucian Carp (Carassius auratus) Induced by Saline-Alkaline Environmental Stress: From Metabolomic Insight
Authors: Yuan Fangying , Wei Xiaofeng , Li Dongping , Jin Xiaofeng , Wang Jing , Sun Yanchun
Published: December 2024

Objectives: The salinization of the water environment worldwide is increasing, which has brought great challenges to the sustainability of fish farming of aquatic animals. Methods: Three NaHCO3 concentration groups (0 mmol/L, 20 mmol/L, and 60 mmol/L) were set up in this study to investigate growth and metabolic differences between diploid and triploid crucian carp under saline-alkaline stresses. Purpose: This study utilized UPLC-QTOF/MS metabolomics to analyze significant metabolites and metabolic pathways in the serum of diploid and triploid crucian carp, exposing them to different NaHCO3 concentrations in saline-alkaline habitats, elucidating the mechanism of their metabolic differences. Results: Results revealed that in the CA20 group, diploid and triploid crucian carp shared 69 differential metabolites, primarily enriched in pathways such as sphingolipid metabolism, glycerophospholipid metabolism, and linoleic acid metabolism. In the CA60 group, 46 differentially metabolites (DMs) were identified, mainly enriched in pathways such as linoleic acid metabolism, unsaturated fatty acid biosynthesis and sphingolipid metabolism. Conclusions: The analysis indicated that under different carbonate-saline-alkaline concentrations, diploid and triploid crucian carp primarily enriched in metabolic pathways such as glycerophospholipid metabolism, sphingolipid metabolism, and unsaturated fatty acid biosynthesis. With increasing carbonate-alkaline concentrations, hemolytic phospholipids associated with cell apoptosis were significantly upregulated and sphingolipid metabolism related to inflammation was more significantly enriched in triploid crucian carp, indicating that triploid crucian carp exhibited significant sensitivity to high carbonate-saline-alkaline stress and poorer carbonate-saline-alkaline tolerance. The results of this study provided a scientific theoretical basis for the later cultivation and aquaculture research of saline-alkaline-tolerant fish species.
Lab-on-a-Chip Devices for Nucleic Acid Analysis in Food Safety
Authors: Lee Inae , Kim Hae-Yeong
Published: December 2024

Lab-on-a-chip (LOC) devices have been developed for nucleic acid analysis by integrating complex laboratory functions onto a miniaturized chip, enabling rapid, cost-effective, and highly sensitive on-site testing. This review examines the application of LOC technology in food safety, specifically in the context of nucleic acid-based analyses for detecting pathogens and contaminants. We focus on microfluidic-based LOC devices that optimize nucleic acid extraction and purification on the chip or amplification and detection processes based on isothermal amplification and polymerase chain reaction. We also explore advancements in integrated LOC devices that combine nucleic acid extraction, amplification, and detection processes within a single chip to minimize sample preparation time and enhance testing accuracy. The review concludes with insights into future trends, particularly the development of portable LOC technologies for rapid and efficient nucleic acid testing in food safety.
Improvement of the Thermal Performance of the GaN-on-Si Microwave High-Electron-Mobility Transistors by Introducing a GaN-on-Insulator Structure
Authors: Hao Lu , Liu Zhihong , Du Hanghai , Zhao Shenglei , Wang Han , Zhang Jincheng , Hao Yue
Published: December 2024

GaN-on-Si high-electron-mobility transistors have emerged as the next generation of high-powered and cost-effective microwave devices; however, the limited thermal conductivity of the Si substrate prevents the realization of their potential. In this paper, a GaN-on-insulator (GNOI) structure is proposed to enhance the heat dissipation ability of a GaN-on-Si HEMT. Electrothermal simulation was carried out to analyze the thermal performance of the GNOI-on-Si HEMTs with different insulator dielectrics, including SiO2, SiC, AlN, and diamond. The thermal resistance of the HEMTs was found to be able to be obviously reduced and the DC performance of the device can be obviously improved by removing the low-thermal-conductivity III-nitride transition layer and forming a GNOI-on-Si structure with SiC, AlN, or diamond as the bonding insulator dielectrics.
Microfluidic Monodispersed Microbubble Generation for Production of Cavitation Nuclei
Authors: Ning Renjie , Acree Blake , Wu Mengren , Gao Yuan
Published: December 2024

Microbubbles, acting as cavitation nuclei, undergo cycles of expansion, contraction, and collapse. This collapse generates shockwaves, alters local shear forces, and increases local temperature. Cavitation causes severe changes in pressure and temperature, resulting in surface erosion. Shockwaves strip material from surfaces, forming pits and cracks. Prolonged cavitation reduces the mechanical strength and fatigue life of materials, potentially leading to failure. Controlling bubble size and generating monodispersed bubbles is crucial for accurately modeling cavitation phenomena. In this work, we generate monodispersed microbubbles with controllable size using a novel and low-cost microfluidic method. We created an innovative T-junction structure that controls the two-phase flow for tiny, monodispersed bubble generation. Monodisperse microbubbles with diameters below one-fifth of the channel width (W = 100 µm) are produced due to the controlled pressure gradient. This microstructure, fabricated by a CNC milling technique, produces 20 μm bubbles without requiring high-resolution equipment and cleanroom environments. Bubble size is controlled with gas and liquid pressure ratio and microgeometry. This microbubble generation method provides a controllable and reproducible way for cavitation research.
Assessment of the Variability in the Occurrence of PFAS in Fish Tissues from Selected Fisheries in the Baltic Sea
Authors: Kuc Joanna , Grochowalska Iwona , Thomas Maciej , Zalewska Tamara , Rybka-Murat Marta
Published: December 2024

In this study, the results of a comprehensive assessment of the variability in the occurrence of ten perfluorinated compounds (PFAS) in fish tissues originating from 2014 to 2019 from six fisheries in the Baltic Sea are presented. A total of 360 fish samples of three species (perch, herring and flatfish) were analysed. For the determination of PFAS, both linear and branched stereoisomers, LC–ESI–MS/MS technique preceded by simultaneous SPE isolation was validated and applied. The total concentration of all determined PFAS compounds shows that the highest levels were observed in the Szczecin Lagoon (4.8 ± 0.7 µg/kg) and the lowest in the Pomeranian Bay (1.9 ± 0.1 µg/kg). In most samples, the dominant compound was perfluorooctane sulfonic acid (PFOS). The present research enabled the assessment of the variability in the occurrence of PFAS stereoisomers in marine fish.
Diluting Ionic Liquids with Small Functional Molecules of Polypropylene Carbonate to Boost the Photovoltaic Performance of Perovskite Solar Cells
Authors: Yang Shuo , Chi Shaohua , Qi Youshuai , Li Kaiyue , Zhang Xiang , Gao Xinru , Yang Lili , Yang Jinghai
Published: December 2024

It is necessary to overcome the relatively low conductivity of ionic liquids (ILs) caused by steric hindrance effects to improve their ability to passivate defects and inhibit ion migration to boost the photovoltaic performance of perovskite solar cells (PSCs). Herein, we designed and prepared a kind of low-concentration 1-butyl-3-methylimidazolium tetrafluoroborate (BMIMBF4) diluted with propylene carbonate (PC) via an ultrasonic technique (PC/IL). The decrease in the decomposition temperature related to the IL part and the increase in the sublimation temperature related to the PC part facilitated the use of PC/IL to effectively delay the crystallization process and passivate the defects in multiple ways to obtain high-quality perovskite films. Moreover, the increased conductivity of PC/IL and the more matched band alignment accelerated electron transport and collection. Finally, the MAPbI3- and CsMAFA-based PSCs achieved PCE values of 20.87% and 23.29%, respectively, and their stabilities were greatly improved. This work provides a promising approach to optimizing ILs to achieve multiple functions and boost the performance of PSCs.
Raman Spectroscopic Analysis of Molecular Structure and Mechanical Properties of Hypophosphatasia Primary Tooth
Authors: Imamura Hayata , Adachi Tetsuya , Zhu Wenliang , Yamamoto Toshiro , Kanamura Narisato , Onoda Hiroaki , Nakamura-Takahashi Aki , Kasahara Masataka , Nakada Masaru , Sato Hideo , Pezzotti Giuseppe
Published: December 2024

Mild hypophosphatasia (HPP) can be difficult to distinguish from other bone disorders in the absence of typical symptoms such as the premature loss of primary teeth. Therefore, this study aimed to analyze the crystallinity of hydroxyapatite (HAp) and the three-dimensional structure of collagen in HPP teeth at the molecular level and to search for new biomarkers of HPP. Raman spectroscopy was used to investigate the molecular structure, composition, and mechanical properties of primary teeth from healthy individuals and patients with HPP. The results showed that the crystallinity of HAp decreased and the carbonate apatite content increased in the region near the dentin–enamel junction (DEJ) of HPP primary teeth. X-ray diffraction (XRD) analyses confirmed a decrease in HAp crystallinity near the DEJ, and micro-computed tomography (CT) scanning revealed a decrease in mineral density in this region. These results suggest incomplete calcification in HPP primary dentin and may contribute to the development of diagnostic and therapeutic agents.
Novel 4-alkoxy Meriolin Congeners Potently Induce Apoptosis in Leukemia and Lymphoma Cells
Authors: Krings Karina S. , Wassenberg Tobias R. , Cea-Medina Pablo , Schmitt Laura , Lechtenberg Ilka , Llewellyn Tanya R. , Qin Nan , Gohlke Holger , Wesselborg Sebastian , Müller Thomas J. J.
Published: December 2024

Meriolins (3-(pyrimidin-4-yl)-7-azaindoles) are synthetic hybrids of the naturally occurring alkaloids variolin and meridianin and display a strong cytotoxic potential. We have recently shown that the novel derivative meriolin 16 is highly cytotoxic in several lymphoma and leukemia cell lines as well as in primary patient-derived lymphoma and leukemia cells and predominantly targets cyclin-dependent kinases (CDKs). Here, we efficiently synthesized nine novel 2-aminopyridyl meriolin congeners (3a–3i), i.e., pyrimeriolins, using a one-pot Masuda borylation-Suzuki coupling (MBSC) sequence, with eight of them bearing lipophilic alkoxy substituents of varying length, to systematically determine the influence of the alkoxy sidechain length on the biological activity. All the synthesized derivatives displayed a pronounced cytotoxic potential, with six compounds showing IC50 values in the nanomolar range. Derivatives 3b–3f strongly induced apoptosis and activated caspases with rapid kinetics within 3–4 h in Jurkat leukemia and Ramos lymphoma cells. The induction of apoptosis by the most potent derivative 3e was mediated by the intrinsic mitochondrial death pathway, as it was blocked in caspase-9 deficient and Apaf-1 knockdown Jurkat cells. However, as recently shown for meriolin 16, derivative 3e was able to induce apoptosis in the Jurkat cells overexpressing the antiapoptotic protein Bcl-2. Since tumor cells often inactivate the intrinsic mitochondrial apoptosis pathway (e.g., by overexpression of Bcl-2), these meriolin congeners represent promising therapeutic agents for overcoming therapeutic resistance.
Insights into the C-Cl Bond Breaking in Epichlorohydrin Induced by Low Energy (<10 eV) Electrons
Authors: Abdoul-Carime Hassan , Castel Louisa , Rabilloud Franck
Published: December 2024

Epichlorohydrin is used as an intermediate for the synthesis of polymers and, more particularly, epoxy adhesives. The traditional process involves the cleavage of the carbon-chlorine bond in an alkaline solution. Here, we investigate the breakage of this bond induced by low-energy (<10 eV) electrons. We show the production of the chlorine anion via a resonant process at different energies. The experimental observations are completed by quantum chemistry calculations of the involved molecular orbitals in the formation of the precursor temporary anions, and their decay mechanisms are discussed in terms of the complex potential energy curve crossing network. The gained information may potentially contribute to a strategy of synthesis by other means where low-energy electrons are implicated, i.e., cold plasmas or even scanning tunnelling microscope for which the bond breakage can be controlled by the energy of the colliding electrons.
Apremilast Cocrystals with Phenolic Coformers
Authors: Naumkina Yelizaveta , Kratochvíl Bohumil , Korotkova Elena , Čejka Jan
Published: December 2024

Apremilast (APR) is an anti-inflammatory drug commonly used in the treatment of psoriasis. In efforts to enhance its solubility, several cocrystals with similar structural features have been developed. This study investigates the cocrystallization of APR with four phenolic-type coformers: phenol, catechol, pyrogallol, and hydroxyquinol. These coformers differ in the number and position of their hydroxyl groups, with their melting points varying by as much as 100 °C. Four novel cocrystal forms were synthesized, purified, and characterized using X-Ray diffraction and thermal analysis techniques. Surprisingly, the resulting cocrystals exhibited minimal differences in their melting points. The molecular packing of APR appears to limit the network-forming potential of the hydroxyl groups, a conclusion supported by the solved crystal structures, Hirshfeld surface analysis, and differential scanning calorimetry (DSC) results.
Establishment of Stable Knockdown of MACC1 Oncogene in Patient-Derived Ovarian Cancer Organoids
Authors: Hierlmayer Sophia , Hladchenko Liliia , Reichenbach Juliane , Klein Christoph , Mahner Sven , Trillsch Fabian , Kessler Mirjana , Chelariu-Raicu Anca
Published: December 2024

High-grade serous ovarian cancer (HGSOC) remains the most lethal gynecological malignancy, and there is still an unmet medical need to deepen basic research on its origins and mechanisms of progression. Patient-derived organoids of high-grade serous ovarian cancer (HGSOC-PDO) are a powerful model to study the complexity of ovarian cancer as they maintain, in vitro, the mutational profile and cellular architecture of the cancer tissue. Genetic modifications by lentiviral transduction allow novel insights into signaling pathways and the potential identification of biomarkers regarding the evolution of drug resistance. Here, we provide an in-depth and detailed protocol to successfully modify the gene expression of HGSOC-PDOs by lentiviral transduction. As an example, we validate our protocol and create a stable knockdown of the MACC1 oncogene with an efficacy of ≥72% in two HGSOC-PDO lines, which remained stable for >3 months in culture. Moreover, we explain step-by-step the sample preparation for the validation procedures on transcriptional (qPCR) and protein (Western Blot) levels. Sustained downregulation of specific genes by lentiviral transduction enables the analysis of the resulting phenotypic and morphological changes. It serves as a valuable in-vitro model to study the mechanisms of ovarian cancer pathogenesis and allows for the evaluation of therapeutic approaches.
Evaluation of Protocols for DNA Extraction from Individual Culex pipiens to Assess Pyrethroid Resistance Using Genotyping Real-Time Polymerase Chain Reaction
Authors: Congiu Ilaria , Cugini Elisa , Smedile Daniele , Romiti Federico , Iurescia Manuela , Donati Valentina , De Liberato Claudio , Battisti Antonio
Published: December 2024

Culex pipiens is a major vector of pathogens, including West Nile and Usutu viruses, that poses a significant public health risk. Monitoring pyrethroid resistance in mosquito populations is essential for effective vector control. This study aims to evaluate four DNA extraction protocols—QIAsymphony, DNAzol® Direct reagent, PrepMan® Ultra Sample Preparation Reagent (USPR), and Chelex® 100—to identify an optimal method to extract DNA from individual Culex pipiens, as part of a high-throughput surveillance of pyrethroid resistance using Real-Time Genotyping PCR. The target is the L1014F mutation in the voltage-sensitive sodium channel (VSSC) gene, which confers knockdown (kdr) resistance to pyrethroids. Mosquitoes were collected from wintering and summer habitats in Lazio and Tuscany, Italy, and DNA was extracted using the four methods. The quality, quantity, extraction time, and cost of the DNA were compared among the various methods. The PrepMan® USPR protocol was the most efficient, providing high-quality DNA with a 260/280 purity ratio within the optimal range at the lowest cost and in a short time. This method also demonstrated the highest amplification success rate (77%) in subsequent real-time PCR assays, making it the preferred protocol for large-scale genotyping studies.
Bacterial Outer Membrane Vesicle (OMV)-Encapsulated TiO2 Nanoparticles: A Dual-Action Strategy for Enhanced Radiotherapy and Immunomodulation in Oral Cancer Treatment
Authors: Kan Shun-An , Zhang Li-Wen , Wang Yu-Chi , Chiang Cheng-Yu , Chen Mei-Hsiu , Huang Shih-Hao , Chen Ming-Hong , Liu Tse-Ying
Published: December 2024

Oral squamous-cell carcinoma (OSCC) poses significant treatment challenges due to its high recurrence rates and the limitations of current therapies. Titanium dioxide (TiO2) nanoparticles are promising radiosensitizers, while bacterial outer membrane vesicles (OMVs) are known for their immunomodulatory properties. This study investigates the potential of OMV-encapsulated TiO2 nanoparticles (TiO2@OMV) to combine these effects for improved OSCC treatment. TiO2 nanoparticles were synthesized using a hydrothermal method and encapsulated within OMVs derived from Escherichia coli. The TiO2@OMV carriers were evaluated for their ability to enhance radiosensitivity and stimulate immune responses in OSCC cell lines. Reactive oxygen species (ROS) production, macrophage recruitment, and selective cytotoxicity toward cancer cells were assessed. TiO2@OMV demonstrated significant radiosensitization and immune activation compared to unencapsulated TiO2 nanoparticles. The system selectively induced cytotoxicity in OSCC cells, sparing normal cells, and enhanced ROS generation and macrophage-mediated antitumor responses. This study highlights TiO2@OMV as a dual-action therapeutic platform that synergizes radiotherapy and immunomodulation, offering a targeted and effective strategy for OSCC treatment. The approach could improve therapeutic outcomes and reduce the adverse effects associated with conventional therapies.
Macronutrient Intake and Food Categories’ Contribution to Daily Energy Intake According to BMI in Primary School Children in Croatia
Authors: Šoher Lidija , Čačić Kenjerić Daniela , Pavlić Martina , Rumbak Ivana , Šarlija Nataša , Ilić Ana , Sokolić Darja
Published: December 2024

Background: Nutritional status in childhood is associated with a number of short- and long-term health effects. The rising prevalence of childhood obesity highlights the necessity of understanding dietary patterns in children. The study provides an assessment of energy and macronutrient intake and food categories’ contribution to energy intake in Croatian primary school children, according to BMI status. Methods: To assess dietary habits, results of the National Food Consumption Survey on Infants and Children based on EU Menu methodology (OC/EFSA/DATA/2016/02 CT3) were used. The sample included 476 children, aged 6 to under 10 years. Results: Results indicated that one in four children was overweight or obese (27.7%). In total, the mean energy intake was 1598.4 ± 380.3 kcal/day, with 30.7% of the children above the recommended energy intake. Cereals, cereal products, and potato food category were the primary sources of energy, which is in line with the recommendations, with protein and fat intakes exceeding recommended levels. Substantial contribution of sweets and low contribution of fruits and vegetables were observed across all BMI categories, with the difference in energy contribution of fruits (p = 0.041) and vegetables (p = 0.033). The meat, poultry, fish, and eggs category were the contributors to energy intake from protein and fat, in the majority of BMI groups. Conclusions: In the obese group, higher energy intake from certain food subgroups was recorded, stressing the need for a more detailed dietary assessment. The study’s cross-sectional design limits causal inferences, indicating a need for future longitudinal research to better understand the dynamics of dietary patterns and BMI status in primary school children.
The Gut Microbiota’s Role in Neurological, Psychiatric, and Neurodevelopmental Disorders
Authors: Charitos Ioannis Alexandros , Inchingolo Angelo Michele , Ferrante Laura , Inchingolo Francesco , Inchingolo Alessio Danilo , Castellaneta Francesca , Cotoia Antonella , Palermo Andrea , Scacco Salvatore , Dipalma Gianna
Published: December 2024

Aim: This article aims to explore the role of the human gut microbiota (GM) in the pathogenesis of neurological, psychiatric, and neurodevelopmental disorders, highlighting its influence on health and disease, and investigating potential therapeutic strategies targeting GM modulation. Materials and Methods: A comprehensive analysis of the gut microbiota’s composition and its interaction with the human body, particularly, its role in neurological and psychiatric conditions, is provided. The review discusses factors influencing GM composition, including birth mode, breastfeeding, diet, medications, and geography. Additionally, it examines the GM’s functions, such as nutrient absorption, immune regulation, and pathogen defense, alongside its interactions with the nervous system through the gut–brain axis, neurotransmitters, and short-chain fatty acids (SCFAs). Results: Alterations in the GM are linked to various disorders, including Parkinson’s disease, multiple sclerosis, depression, schizophrenia, ADHD, and autism. The GM influences cognitive functions, stress responses, and mood regulation. Antibiotic use disrupts GM diversity, increasing the risk of metabolic disorders, obesity, and allergic diseases. Emerging therapies such as probiotics, prebiotics, and microbiota transplantation show promise in modulating the GM and alleviating symptoms of neurological and psychiatric conditions. Conclusions. The modulation of the GM represents a promising approach for personalized treatment strategies. Further research is needed to better understand the underlying mechanisms and to develop targeted therapies aimed at restoring GM balance for improved clinical outcomes.
Gut Microbiome Modulation of Glutamate Dynamics: Implications for Brain Health and Neurotoxicity
Authors: Gruenbaum Benjamin F. , Merchant Kiran S. , Zlotnik Alexander , Boyko Matthew
Published: December 2024

The gut–brain axis plays an integral role in maintaining overall health, with growing evidence suggesting its impact on the development of various neuropsychiatric disorders, including depression. This review explores the complex relationship between gut microbiota and glutamate (Glu) regulation, highlighting its effect on brain health, particularly in the context of depression following certain neurological insults. We discuss how microbial populations can either facilitate or limit Glu uptake, influencing its bioavailability and predisposing to neuroinflammation and neurotoxicity. Additionally, we examine the role of gut metabolites and their influence on the blood–brain barrier and neurotransmitter systems involved in mood regulation. The therapeutic potential of microbiome-targeted interventions, such as fecal microbiota transplantation, is also highlighted. While much research has explored the role of Glu in major depressive disorders and other neurological diseases, the contribution of gut microbiota in post-neurological depression remains underexplored. Future research should focus on explaining the mechanisms linking the gut microbiota to neuropsychiatric outcomes, particularly in conditions such as post-stroke depression, post-traumatic brain-injury depression, and epilepsy-associated depression. Systematic reviews and human clinical studies are needed to establish causal relationships and assess the efficacy of microbiome-targeted therapies in improving the neuropsychiatric sequalae after neurological insults.
Obesity and Metabolic Disease Impair the Anabolic Response to Protein Supplementation and Resistance Exercise: A Retrospective Analysis of a Randomized Clinical Trial with Implications for Aging, Sarcopenic Obesity, and Weight Management
Authors: Nilsson Mats I. , Xhuti Donald , de Maat Nicoletta Maria , Hettinga Bart P. , Tarnopolsky Mark A.
Published: December 2024

Background: Anabolic resistance accelerates muscle loss in aging and obesity, thus predisposing to sarcopenic obesity. Methods: In this retrospective analysis of a randomized clinical trial, we examined baseline predictors of the adaptive response to three months of home-based resistance exercise, daily physical activity, and protein-based, multi-ingredient supplementation (MIS) in a cohort of free-living, older males (n = 32). Results: Multiple linear regression analyses revealed that obesity and a Global Risk Index for metabolic syndrome (MetS) were the strongest predictors of Δ% gains in lean mass (TLM and ASM), LM/body fat ratios (TLM/%BF, ASM/FM, and ASM/%BF), and allometric LM (ASMI, TLM/BW, TLM/BMI, ASM/BW), with moderately strong, negative correlations to the adaptive response to polytherapy r = −0.36 to −0.68 (p < 0.05). Kidney function, PA level, and chronological age were only weakly associated with treatment outcomes (p > 0.05). Next, we performed a subgroup analysis in overweight/obese participants with at least one other MetS risk factor and examined their adaptive response to polytherapy with two types of protein-based MIS (PLA; collagen peptides and safflower oil, n = 8, M5; whey/casein, creatine, calcium, vitamin D3, and fish oil, n = 12). The M5 group showed greater improvements in LM (ASM; +2% vs. −0.8%), LM/body fat ratios (ASM/FM; +3.8% vs. −5.1%), allometric LM (ASM/BMI; +1.2% vs. −2.5%), strength (leg press; +17% vs. −1.4%), and performance (4-Step-Stair-Climb time; −10.5% vs. +1.1%) vs. the PLA group (p < 0.05). Bone turnover markers, indicative of bone accretion, were increased pre-to-post intervention in the M5 group only (P1NP; p = 0.036, P1NP/CTX ratio; p = 0.088). The overall anabolic response, as indicated by ranking low-to-high responders for Δ% LM (p = 0.0079), strength (p = 0.097), and performance (p = 0.19), was therefore significantly higher in the M5 vs. PLA group (p = 0.013). Conclusions: Our findings confirm that obesity/MetS is a key driver of anabolic resistance in old age and that a high-quality, whey/casein-based MIS is more effective than a collagen-based alternative for maintaining musculoskeletal health in individuals at risk for sarcopenic obesity, even when total daily protein intake exceeds current treatment guidelines.
A Systematic Review and Meta-Analysis of Type 2 Diabetes Prevention Through Lifestyle Interventions in Women with a History of Gestational Diabetes—A Summary of Participant and Intervention Characteristics
Authors: Ukke Gebresilasea , Boyle Jacqueline , Reja Ahmed , Lee Wai , Chen Mingling , Ko Michelle , Alycia Chelsea , Kwon Jane , Lim Siew
Published: December 2024

Objectives: We aimed to review the effect of lifestyle interventions in women with a history of gestational diabetes mellitus (GDM) based on the participants and intervention characteristics. Methods: We systematically searched seven databases for RCTs of lifestyle interventions published up to 24 July 2024. We included 30 studies that reported the incidence of type 2 diabetes mellitus (T2DM) or body weight. A random effects model was used to calculate the relative risk and mean difference with a 95% confidence interval. Subgroup analyses were conducted for participants’ characteristics (age, body mass index (BMI)) and intervention characteristics according to the Template for Intervention Description and Replication (TIDieR). Results: A greater T2DM risk reduction was seen in trials that started within one year postpartum, in participants with a mean baseline BMI of 30 kg/m2 or more, or based on behavioral change theory. For body weight reduction, studies on participants with a mean baseline BMI of 25 kg/m2 or more or ones that included electronic/mobile delivery (text message, web, phone call) were more effective. Conclusions: Diabetes prevention trials in women with a history of GDM are more effective when commencing within one year postpartum, underpinned by behavior change theory, and in participants with overweight or obesity.
Heat-Killed Lactobacillus delbrueckii subsp. lactis 557 Extracts Protect Chondrocytes from Osteoarthritis Damage by Reducing Inflammation: An In Vitro Study
Authors: Hu Yu-Chen , Huang Tzu-Ching , Hsieh Bau-Shan , Huang Li-Wen , Lin Jin-Seng , Hsu Han-Yin , Lee Chia-Chia , Chang Kee-Lung
Published: December 2024

Background: Osteoarthritis (OA) is a chronic condition characterized by joint pain and disability, driven by excessive oxidative stress and inflammatory cytokine production in chondrocytes, resulting in cell death and cartilage matrix breakdown. Our previous study showed that in monosodium iodoacetate (MIA)-induced OA rats, oral administration of heat-killed Lactobacillus delbrueckii subsp. lactis 557 (LDL557) could significantly decrease OA progression. Methods: Accordingly, we designed an in vitro cell culture study aimed at investigating the effects of heat-killed LDL557 extracts on chondrocytes using SW1353 cells (a human chondrosarcoma cell line) challenged with 5 μM MIA to mimic OA conditions. Results: The results showed that the 10 μg/mL LDL557 extracts protected SW1353 cells from MIA-induced death and reduced extracellular matrix (ECM) loss, as evaluated by toluidine blue O staining and extracellular matrix component synthesis with RT-qPCR measurement. This was achieved by decreasing the expression of MIA-induced pro-inflammatory cytokines, including IL-1β, IL-6, and TNF-α, while slightly increasing the MIA-suppressed expression of the anti-inflammatory cytokine IL-10, which were evidenced by RT-qPCR analysis. Moreover, the RT-qPCR evaluation also indicated that the LDL557 extracts slightly reduced the expression of COX-2 compared with the control, while it did not reduce the MIA-increased expression of microsomal prostaglandin E synthase-1 (mPGES-1). In addition, the LDL557 extracts influenced neither the matrix-degrading protease expressions measured via RT-qPCR nor the oxidative stress measured via fluorescence flow cytometry in the cells with or without the MIA challenge. Conclusions: This study demonstrates that LDL557 extracts may protect chondrocytes from OA damage by reducing inflammation-related factors and thus mitigating cartilage matrix loss, suggesting LDL557 extracts are attractive alternatives for OA applications.
Approach to Epistaxis
Authors: Chowdhury Raisa , Turkdogan Sena , Silver Jennifer A. , Hier Jessica , Bursey Stuart , Quttaineh Danah , Khoury Mark , Himdi Lamiae
Published: December 2024

Epistaxis, commonly referred to as nosebleeds, is a frequent clinical presentation with etiologies spanning from localized trauma to systemic conditions and medication effects. Despite its high prevalence, management approaches vary significantly depending on the cause and severity. To provide a comprehensive review of current management strategies for epistaxis, focusing on initial interventions, evaluation techniques, and preventive measures. A structured review of the literature was conducted to identify effective strategies for the initial management, evaluation, and prevention of epistaxis. Emphasis was placed on practical applications for clinicians in both emergency and outpatient settings. Initial Management: Direct pressure and topical vasoconstrictors remain the first-line interventions. Persistent cases may require nasal packing or cautery. Evaluation: Identification of underlying causes such as hypertension, coagulopathies, and structural nasal abnormalities is crucial, particularly in recurrent or severe cases. Laboratory tests and imaging may aid in diagnosis and management planning. Prevention: Patient education on nasal hygiene, avoidance of nasal trauma, and maintenance of a humidified environment are critical in reducing recurrence. Integrating effective initial management with thorough evaluation and preventive strategies significantly improves patient outcomes.
Asymptomatic Malaria Cases and Plasmodium Species in Mainland Tanzania and Zanzibar Archipelago (Pemba)
Authors: Kołodziej Daria , Wilczyńska Wanesa , Marchelek-Myśliwiec Małgorzata , Świetlik Dariusz , Ammi Heriel Zacharia , Athumani Mohamed Othman , Korzeniewski Krzysztof
Published: December 2024

Malaria remains a major public health threat in Sub-Saharan Africa. According to the World Health Organization (WHO) estimates, Plasmodium falciparum species account for nearly 100% of the malaria cases occurring on the African continent. According to the Centers for Disease Control and Prevention (CDC), falciparum malaria predominates, but non-falciparum species are also present in Africa. The aim of the study was to assess the occurrence of asymptomatic malaria cases, as well as to identify Plasmodium species at two different settings with the lowest index of infections in Tanzania (according to the Tanzanian Ministry of Health < 1%), i.e., on the mainland (Arusha Region) and on the Pemba Island (Zanzibar Archipelago). The study was conducted in June 2023 and involved 722 individuals, including 449 residents of mainland Tanzania and 273 residents of the Zanzibar Archipelago. The screening consisted of two phases. In the first one, which was carried out at two different settings, i.e., in the Karatu Lutheran Hospital (Arusha Region, mainland Tanzania) and the Amal Hospital (Pemba, Zanzibar Archipelago), mRDTs (malaria rapid diagnostic tests) were performed, haemoglobin concentrations were measured, and blood samples for further molecular tests were collected onto Whatman micro cards from each of the individuals involved. In the second phase (conducted in Poland, Europe), RT-PCR tests for malaria were performed. The screening found asymptomatic Plasmodium infections in 4.2% of the study subjects from mainland Tanzania and in 4.8% from the Archipelago. The research confirmed cases of P. falciparum malaria but also found single cases of mixed infections with P. falciparum + P. malariae or P. ovale. The results demonstrated that the occurrence of malaria in northern mainland and Zanzibar Archipelago is higher than the official MoH reports present. The study findings are consistent with the reports by CDC, which suggest that non-falciparum species are also present in Sub-Saharan Africa.
Pentagalloyl Glucose from Bouea macrophylla Suppresses the Epithelial–Mesenchymal Transition and Synergizes the Doxorubicin-Induced Anticancer and Anti-Migration Effects in Triple-Negative Breast Cancer
Authors: Kantapan Jiraporn , Innuan Phattarawadee , Kongkarnka Sarawut , Sangthong Padchanee , Dechsupa Nathupakorn
Published: December 2024

Background: Triple-negative breast cancer (TNBC) represents an aggressive form of breast cancer with few available therapeutic options. Chemotherapy, particularly with drugs like doxorubicin (DOX), remains the cornerstone of treatment for this challenging subtype. However, the clinical utility of DOX is hampered by adverse effects that escalate with higher doses and drug resistance, underscoring the need for alternative therapies. This study explored the efficacy of pentagalloyl glucose (PGG), a natural polyphenol derived from Bouea macrophylla, in enhancing DOX’s anticancer effects and suppressing the epithelial–mesenchymal transition (EMT) in TNBC cells. Methods: This study employed diverse methodologies to assess the effects of PGG and DOX on TNBC cells. MDA-MB231 triple-negative breast cancer cells were used to evaluate cell viability, migration, invasion, apoptosis, mitochondrial membrane potential, and protein expression through techniques including MTT assays, wound healing assays, flow cytometry, Western blotting, and immunofluorescence. Results: Our findings demonstrate that PGG combined with DOX significantly inhibits TNBC cell proliferation, migration, and invasion. PGG enhances DOX-induced apoptosis by disrupting the mitochondrial membrane potential and activating caspase pathways; consequently, the activation of caspase-3 and the cleavage of PARP are increased. Additionally, the study shows that the combination treatment upregulates ERK signaling, further promoting apoptosis. Moreover, PGG reverses DOX-induced EMT by downregulating mesenchymal markers (vimentin and β-catenin) and upregulating epithelial markers (E-cadherin). Furthermore, it effectively inhibits STAT3 phosphorylation, associated with cell survival and migration. Conclusions: These results highlight the potential of PGG as an adjuvant therapy in TNBC treatment. PGG synergizes with DOX, which potentiates its anticancer effects while mitigating adverse reactions.
Vitamin E Improves Cellular and Structural Bone Histomorphometry in an Alcohol-Induced Osteoporosis Rat Model
Authors: Mohamed Norazlina , Ahmed Abukhadir Seham Salem , Syed Hashim Syed Alhafiz , Adnan Nur Sabariah , Aziz Muhamad Arizi , Muhammad Norliza
Published: December 2024

Background: Alcohol-induced osteoporosis is a significant health concern, impairing bone formation and enhancing resorption, thereby weakening skeletal integrity. This study examines the effects of palm vitamin E on bone histomorphometry in a male rat model of alcohol-induced osteoporosis. Methods: Three-month-old Sprague–Dawley rats were randomized into seven groups, with one baseline control group (BC) and six experimental groups undergoing a two-phase treatment. In the first month, the control group received normal saline, while experimental groups received intraperitoneal alcohol (3 g/kg) three times weekly. For the subsequent two months, alcohol treatment continued in one group (A), while others received olive oil (C), saline (AN), alpha-tocopherol (AA), or palm vitamin E (AE) orally. Results: Femur histomorphometric analysis post-sacrifice showed that alcohol exposure significantly decreased osteoblastic activity and impaired bone microarchitecture, evidenced by reduced Ob.S/BS, OS/BS, OV/BV, Tb.Th, BV/TV, and Tb.N, alongside increased Oc.S/BS, ES/BS, and Tb.Sp. Both alpha-tocopherol and palm vitamin E improved bone parameters, with palm vitamin E showing superior efficacy except in OV/BV. Conclusions: These findings suggest that palm vitamin E may offer a therapeutic benefit for mitigating alcohol-induced bone damage.
Integrated Network-Based Analysis of Diseases Associated with Amyloid Deposition Through a Disease–Protein–Drug Network
Authors: Rizou Aikaterini E. I. , Nasi Georgia I. , Apostolakou Avgi E. , Dimopoulos Meletios A. , Kastritis Efstathios , Iconomidou Vassiliki A.
Published: December 2024

Background: At present, the complexity that governs the associations between different biological entities is understood better than ever before, owing to high-throughput techniques and systems biology. Networks of interactions are necessary not only for the visualization of these complex relationships but also because their analysis tends to be valuable for the extraction of novel biological knowledge. Methods: For this reason, we constructed a disease–protein–drug network, focusing on a category of rare protein-misfolding diseases, known as amyloidoses, and on other pathological conditions also associated with amyloid deposition. Apart from the amyloidogenic proteins that self-assemble into fibrils, we also included other co-deposited proteins found in amyloid deposits. Results: In this work, protein–protein, protein–drug, and disease–drug associations were collected to create a heterogenous network. Through disease-based and drug-based analyses, we highlighted commonalities between diseases and proposed an approved drug with prospects of repurposing. Conclusions: The identified disease associations and drug candidates are proposed for further study that will potentially help treat diseases associated with amyloid deposition.
The Role of Antioxidant Plant Extracts’ Composition and Encapsulation in Dietary Supplements and Gemmo-Derivatives, as Safe Adjuvants in Metabolic and Age-Related Conditions: A Review
Authors: Negreanu-Pirjol Bogdan-Stefan , Negreanu-Pirjol Ticuta , Busuricu Florica , Jurja Sanda , Craciunescu Oana , Oprea Ovidiu , Motelica Ludmila , Oprita Elena Iulia , Roncea Florentina Nicoleta
Published: December 2024

Given the current global circumstances, marked by severe environmental pollution—including the contamination of food—along with daily stress and a sedentary lifestyle, many consumers choose to improve their quality of life by using, among others, minimally processed food, food supplements, and gemmo-derivatives. Recent lab and clinical studies have shown the positive impact of specific nutrients with antioxidant capacities in the treatment of several conditions generated by oxidative stress. This paper reviews antioxidant plant extracts utilized as components in various dietary supplements and gemmoderivatives, highlighting their chemical composition and biological properties in preventing diseases caused by oxidative stress. A modern approach to food science brings to the fore the concept of dietary supplements vs. functional food, nutraceuticals, and gemmo-derivatives. The definitions of these terms are not being unanimously regulated in this respect and describe each category of compound and product, also emphasizing the need to implement adequate nutrivigilance. In order to enhance the absorption and bioavailability of dietary supplements and gemmo-derivatives based on antioxidant plant extracts, some encapsulation techniques are outlined.