bluuebunny/crossref_metadata_2025 huggingface dataset:
Immunomodulatory Potential of 6-Gingerol and 6-Shogaol in Lactobacillus plantarum-Fermented Zingiber officinale Extract on Murine Macrophages
Authors: Kim Ji Eun , Park Kwang-Hyun , Park Jinny , Kim Byeong Soo , Kim Geun-Seop , Hwang Dong Geon
Published: February 2025

In this study, we aimed to investigate whether the physiological activity of ethanol extracts of Zingiber officinale was improved after fermentation with Lactobacillus plantarum strains KCTC 3108 (FLP8) and KCL005 (FLP9). Total polyphenol and flavonoid content was substantially increased after fermentation with FLP8 and FLP9 for 48 h and 24 h, respectively, compared with the unfermented control. The 6-gingerol content was significantly increased in FLP9 after 24 h of fermentation, whereas in FLP8, it remained comparable to pre-fermentation levels. The 6-shogaol content significantly increased in FLP8 and FLP9 at 48 h and 24 h, respectively, compared with the pre-fermentation levels. The anti-inflammatory effects were evaluated using RAW 264.7 cells stimulated with lipopolysaccharides. The fermented product of FLP8 at 48 h and FLP9 at 24 h maintained over 80% cell viability at a concentration of 200 µg/mL and significantly reduced nitric oxide production compared to the lipopolysaccharide-stimulated control. Moreover, each extract downregulated pro-inflammatory gene expression. Furthermore, the purified 6-gingerol and 6-shogaol, which were purchased as reference compounds, were included in the fermentation extracts of FLP8 at 48 h and FLP9 at 24 h, and both inhibited cell migration in a dose-dependent manner without any cytotoxicity. In conclusion, the fermentation of Z. officinale with these L. plantarum strains enhanced its antioxidant and anti-inflammatory activities, with significant increases in bioactive compound content.
GPCRVS - AI-driven Decision Support System for GPCR Virtual Screening
Authors: Latek Dorota , Prajapati Khushil , Dragan Paulina , Merski Matthew , Osial Przemysław
Published: February 2025

G protein-coupled receptors (GPCRs) constitute the largest and most frequently used family of molecular drug targets. The simplicity of GPCR drug design results from their common seven-transmembrane-helix topology and well-understood signaling pathways. GPCRs are extremely sensitive to slight changes in the chemical structure of compounds, which allows for the reliable design of highly selective and specific drugs. Only recently has the number of GPCR structures, both in their active and inactive conformations, together with their active ligands, become sufficient to comprehensively apply machine learning in decision support systems to predict compound activity in drug design. Here, we describe GPCRVS, an efficient machine learning system for the online assessment of the compound activity against several GPCR targets, including peptide- and protein-binding GPCRs, which are the most difficult for virtual screening tasks. As a decision support system, GPCRVS evaluates compounds in terms of their activity range, the pharmacological effect they exert on the receptor, and the binding mode they could demonstrate for different types and subtypes of GPCRs. GPCRVS allows for the evaluation of compounds ranging from small molecules to short peptides provided in common chemical file formats. The results of the activity class assignment and the binding affinity prediction are provided in comparison with predictions for known active ligands of each included GPCR. Multiclass classification in GPCRVS, handling incomplete and fuzzy biological data, was validated on ChEMBL and Google Patents-retrieved data sets for class B GPCRs and chemokine CC and CXC receptors.
Correction: Flis et al. The Effect of Long-Lasting Swimming on Rats Skeletal Muscles Energy Metabolism after Nine Days of Dexamethasone Treatment. Int. J. Mol. Sci. 2022, 23, 748
Authors: Flis Damian Jozef , Bialobrodzka Emilia Gabriela , Rodziewicz-Flis Ewa Aleksandra , Jost Zbigniew , Borkowska Andzelika , Ziolkowski Wieslaw , Kaczor Jan Jacek
Published: February 2025

Due to the lack of enzyme 17-α hydroxylase, rats and mice cannot produce appreciable cortisol; however, low cortisol concentrations are detectable in these rodents’ blood [...]
Vagus Nerve Mediated Liver-Brain-Axis Is a Major Regulator of the Metabolic Landscape in the Liver
Authors: Brito Camila F. , Fonseca Roberta C. , Rodrigues-Ribeiro Lucas , Guimarães João S. F. , Vaz Bruna F. , Tofani Gabriel S. S. , Batista Ana C. S. , Diniz Ariane B. , Fernandes Paola , Nunes Núbia A. M. , Pessoa Rafaela M. , Oliveira Amanda C. C. , Lula Ivana S. , Cardoso Valbert N. , Fernandes Simone O. A. , Poletini Maristela O. , Alvarez-Leite Jacqueline I. , Menezes Gustavo B. , Ferreira Adaliene V. M. , Magalhães Mariana T. Q. , Gorshkov Vladimir , Kjeldsen Frank , Verano-Braga Thiago , Araujo Alan M. , Oliveira André G.
Published: February 2025

The liver serves as a major energetic reservoir for other tissues and its metabolic function is controlled by humoral and neural factors. The vagus nerve innervating the gastrointestinal tract plays an important role in regulating peripheral metabolism and energy expenditure. Although the liver receives vagus nerve fibers, the impact of this circuitry in the regulation of hepatic metabolism is still poorly understood. Herein, we used a combination of quantitative proteomics and in vivo imaging techniques to investigate the impact of the vagus nerve on liver metabolism in male mice. Liver-brain axis was impaired by vagotomy (VNX) or knocking down of the vesicular acetylcholine transporter (VAChT-KD). Mice were challenged with high carbohydrate or high-fat feeding. The vagus nerve shapes the metabolic framework of the liver, as vagotomy led to a significant alteration of the hepatic proteome landscape. Differential protein expression and pathway enrichment analyses showed that glycolytic and fatty acid biosynthesis were increased following VNX, whereas β-oxidation was decreased. These results were corroborated in VAChT-KD mice. This metabolic shift facilitated lipid accumulation in hepatocytes in mice fed with a standard commercial diet. Furthermore, VNX worsened liver steatosis following high-carbohydrate or high-fat dietary challenges. This study describes the liver-brain axis mediated by the vagus nerve as an important regulator of the hepatic metabolic landscape.
Molecular Mechanism of Vine Tea Dihydromyricetin Extract on Alleviating Glucolipid Metabolism Disorder in db/db Mice: Based on Liver RNA-Seq and TLR4/MyD88/NF-κB Pathway
Authors: Zhou Xixin , Liu Xin , Yi Yuhang , Chen Shiyun , Zhang Yi , Fan Wei , Lv Chenghao , Qin Si
Published: February 2025

The primary active compound in vine tea is dihydromyricetin (DMY), which has a longstanding history as a dietary supplement and traditional ethnic medicine. However, the precise molecular mechanism by which vine tea dihydromyricetin extract (VDMY) regulates glucolipid metabolic disorder remains unclear. In this study, we first assessed the effect of VDMY on various physiological parameters in db/db mice, followed by RNA sequencing (RNA-seq) to identify key signaling pathways affected by VDMY in liver tissues. We also examined the impact of VDMY on the liver’s TLR4/MyD88/NF-κB and FOXO1 pathways using Western blotting. Our results showed that VDMY significantly reduced fasting blood glucose (FBG), total cholesterol (TC), triglycerides (TGs), and low-density lipoprotein cholesterol (LDL-C), while increasing high-density lipoprotein cholesterol (HDL-C) levels. Additionally, VDMY enhanced the liver’s antioxidant capacity by upregulating superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH), while lowering malondialdehyde (MDA), alanine aminotransferase (ALT), and aspartate aminotransferase (AST), thus alleviating liver damage. RNA-seq analysis further revealed that VDMY influenced multiple biological processes, including transcription, glycolysis, gluconeogenesis, and redox reactions, suggesting that its effects may be mediated through the TLR4/MyD88/NF-κB and FOXO1 pathways. Additionally, Western blot analysis revealed that VDMY effectively downregulated the expressions of TLR4, MyD88, NF-κB, and FOXO1 proteins in the liver of db/db mice, indicating that VDMY could target these pathways to intervene glucolipid metabolism dysfunction.
A Retrospective Analysis of the Changes in Prediabetes-Associated Markers of Thyroid Function in Patients from Durban, South Africa
Authors: Aswani Hasnaa Satar , Mdluli Wendy , Khathi Andile
Published: February 2025

Thyroid dysfunction and type 2 diabetes melittus (T2DM) are two of the most common endocrine disorders, and the emerging condition of prediabetes necessitates additional research to better understand the complex interactions between thyroid hormones, metabolic regulation, and the progression from prediabetes to T2DM. This study sought to investigate changes in selected markers of thyroid function in patients with pre-diabetes. Upon obtaining ethics permission, blood samples were collected from patients in King Edward Hospital in Durban, South Africa. The samples were classified as non-diabetic, pre-diabetic, and type 2 diabetic using the ADA guidelines. The thyroid stimulating hormone (TSH), thyroxine (T4) triiodothyronine (T3), Thyroglobulin (TG), and thyroid peroxidase antibody (TPOAb) concentrations were determined in these samples. The results showed elevated TSH, decreased T3 and T4, decreased thyroglobulin (Tg), and elevated TPOAb in the prediabetic group which became considerably pronounced with the shift to T2DM. The alterations in these markers during prediabetes may indicate an early stage of thyroid dysfunction necessitating further investigation as these alterations become more pronounced during type 2 diabetes mellitus.
Euphraticanoids N–T: Aromadendrane-Type Diterpenes and Sesquiterpenes with Fungicidal Activities from Populus euphratica Resins
Authors: Jiang Qinbin , Liu Yun-Yun , Huang Danling , Cheng Yong-Xian
Published: February 2025

Seven previously undescribed terpenoids, including five prenylaromadendrane-type diterpenes euphraticanoids N–R (1–5) and two aromadendrane-type sesquiterpenes, euphraticanoids S and T (6 and 7), were isolated from Populus euphratica resins. Their structures, including their absolute configurations, were elucidated by HRESIMS and spectroscopic analysis, ECD calculations, and crystallographic methods. In addition, an evaluation of the fungicidal activities of compound 1 was carried out, resulting in the discovery of 1 as a fungicidal candidate lead compound with an EC50 of 15.7 and 68.6 mg/L against Curvularia mebaldsii and Fusarium graminearum, respectively.
Targeting Glucosylceramide Synthase: Innovative Drug Repurposing Strategies for Lysosomal Diseases
Authors: Canini Giorgia , Mazzinelli Elena , Nocca Giuseppina , Lattanzi Wanda , Arcovito Alessandro
Published: February 2025

Sphingolipidoses, a subgroup of lysosomal storage diseases (LSDs), are rare and debilitating disorders caused by defects in sphingolipid metabolism. Despite advancements in treatment, therapeutic options remain limited. Miglustat, a glucosylceramide synthase EC 2.4.1.80 (GCS) inhibitor, is one of the few available pharmacological treatments; however, it is associated with significant adverse effects that impact patients’ quality of life. Drug repurposing offers a promising strategy to identify new therapeutic agents from approved drugs, expanding treatment options for rare diseases with limited therapeutic alternatives. This study aims to identify potential alternative inhibitors of GCS through a drug-repurposing approach, using computational and experimental methods to assess their therapeutic potential for sphingolipidoses. A library of approved drugs was screened using advanced computational techniques, including molecular docking, molecular dynamics simulations, and metadynamics, to identify potential GCS inhibitors. Promising candidates were selected for further in vitro validation to evaluate their inhibitory activity and potential as therapeutic alternatives to Miglustat. Computational screening identified several potential GCS inhibitors, with Dapagliflozin emerging as the most promising candidate. Experimental validation confirmed its efficacy, revealing a complementary mechanism of action to Miglustat while potentially offering a more favorable side effect profile. This study underscores the utility of computational and experimental methodologies in drug repurposing for rare diseases. The identification of Dapagliflozin as a potential GCS inhibitor provides a foundation for further preclinical and clinical evaluation, supporting its potential application in the treatment of sphingolipidoses.
Diabetes-Driven Atherosclerosis: Updated Mechanistic Insights and Novel Therapeutic Strategies
Authors: Karakasis Paschalis , Theofilis Panagiotis , Patoulias Dimitrios , Vlachakis Panayotis K. , Antoniadis Antonios P. , Fragakis Nikolaos
Published: February 2025

The global rise in diabetes prevalence has significantly contributed to the increasing burden of atherosclerotic cardiovascular disease (ASCVD), a leading cause of morbidity and mortality in this population. Diabetes accelerates atherosclerosis through mechanisms such as hyperglycemia, oxidative stress, chronic inflammation, and epigenetic dysregulation, leading to unstable plaques and an elevated risk of cardiovascular events. Despite advancements in controlling traditional risk factors like dyslipidemia and hypertension, a considerable residual cardiovascular risk persists, highlighting the need for innovative therapeutic approaches. Emerging treatments, including sodium–glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, epigenetic modulators, and RNA-based therapies, are showing promise in addressing the unique challenges of diabetes-associated ASCVD. Precision medicine strategies, such as nanoparticle-based drug delivery and cell-specific therapies, offer further potential for mitigating cardiovascular complications. Advances in multiomics and systems biology continue to deepen our understanding of the molecular mechanisms driving diabetes-associated atherosclerosis. This review synthesizes recent advances in understanding the pathophysiology and treatment of diabetes-related atherosclerosis, offering a roadmap for future research and precision medicine approaches to mitigate cardiovascular risk in this growing population.
Calcium Signaling Is a Universal Carbon Source Signal Transducer and Effects an Ionic Memory of Past Carbon Sources
Authors: Simpson-Lavy Kobi , Kupiec Martin
Published: February 2025

Glucose is the preferred carbon source for most cells. However, cells may encounter other carbon sources that can be utilized. How cells match their metabolic gene expression to their carbon source, beyond a general glucose repressive system (catabolite repression), remains little understood. By studying the effect of up to seven different carbon sources on Snf1 phosphorylation and on the expression of downstream regulated genes, we searched for the mechanism that identifies carbon sources. We found that the glycolysis metabolites glucose-6-phosphate (G6P) and glucose-1-phosphate (G1P) play a central role in the adaptation of gene expression to different carbon sources. The ratio of G1P and G6P activates analogue calcium signaling via the proton-exporter Pma1 to regulate downstream genes. The signaling pathway bifurcates with calcineurin-reducing ADH2 (alcohol dehydrogenase) expression and with Cmk1-increasing ZWF1 (glucose-6-phosphate dehydrogenase) expression. Furthermore, calcium signaling is not only regulated by the present carbon source; it is also regulated by past carbon sources. We were able to manipulate this ionic memory mechanism to obtain high expression of ZWF1 in media containing galactose. Our findings provide a universal mechanism by which cells respond to all carbon sources.
Development of a Pre-Modification Strategy to Overcome Restriction–Modification Barriers and Enhance Genetic Engineering in Lactococcus lactis for Nisin Biosynthesis
Authors: Chen Chen , Zhang Yue , Chen Ruiqi , Liu Ke , Wu Hao , Qiao Jianjun , Caiyin Qinggele
Published: February 2025

Due to the barriers imposed by the restriction–modification (RM) system, Nisin-producing industrial strains of Lactococcus lactis often encounter low transformation efficiency, which seriously hinders the widespread application of genetic engineering in non-model L. lactis. Herein, we present a novel pre-modification strategy (PMS) coupled with optimized plasmid delivery systems designed to systematically evade RM barriers and substantially improve Nisin biosynthesis in L. lactis. Through the use of engineered Escherichia coli strains with methylation profiles specifically optimized for L. lactis C20, we have effectively evaded RM barriers, thereby facilitating the efficient introduction of large Nisin biosynthetic gene clusters into L. lactis. The PMS tools, which significantly improve the transformation efficiency (~103 transformants per microgram of DNA), have been further improved in combination with a Rolling Circle Amplification, resulting in a higher enhancement in transformation efficiency (~104 transformants per microgram of DNA). Using this strategy, large Nisin biosynthetic gene clusters and the expression regulation of all genes within the cluster were introduced and analyzed in L. lactis, leading to a highest Nisin titer of 11,052.9 IU/mL through a fed-batch fermentation in a 5 L bioreactor. This is the first systematic report on the expression regulation and application of a complete Nisin biosynthesis gene cluster in L. lactis. Taken together, our studies provide a versatile and efficient strategy for systematic evasion and enhancement of RM barriers and Nisin biosynthesis, thereby paving the way for genetic modification and metabolic engineering in L. lactis.
Coupled Influence of Magnetic Biochar and Solution Chemistries on Retention and Release of Nanoplastics in Porous Media
Authors: Qin Yan , Liang Yan , Peng Yongtao
Published: February 2025

Magnetic biochar (MBC), as an environmentally friendly material, has been extensively used for the remediation of soil and groundwater contamination. The retention and release of nanoplastics (NPs) with carboxyl (NPs-COOH) or amino functionalization (NPs- NH2) in saturated porous media were investigated under varying conditions of ionic strength (IS), MBC addition, humic acid (HA) concentration, and cation types. The reversible and irreversible retention of NPs was examined by altering the IS, increasing the solution pH, and inducing cation exchange. The results revealed that MBC enhanced the surface roughness of the media, thereby inhibiting NPs’ transport. The HA promoted NPs-NH2 transport more effectively than NPs-COOH due to electrostatic repulsion, steric hindrance, and competition for deposition sites. Under a reduced IS and increased pH, a portion of the retained NPs was released, with NPs-NH2 showing a greater release than NPs-COOH, indicating reversible retention. Additionally, the stronger charge-shielding and cation-bridging effects of Ca2⁺ significantly enhanced the retention of NPs. Cation exchange resulted in less NPs being released, as most were irreversibly retained in deeper primary minima. However, a small number of retained NPs were remobilized by electrical double layer expansion, surface deprotonation, and cation exchange, indicating reversible retention. These findings provide valuable insights into the fate of NPs in the environment.
Progress in AAV-Mediated In Vivo Gene Therapy and Its Applications in Central Nervous System Diseases
Authors: Wang Shuming , Xiao Lin
Published: February 2025

As the blood–brain barrier (BBB) prevents molecules from accessing the central nervous system (CNS), the traditional systemic delivery of chemical drugs limits the development of neurological drugs. However, in recent years, innovative therapeutic strategies have tried to bypass the restriction of traditional drug delivery methods. In vivo gene therapy refers to emerging biopharma vectors that carry the specific genes and target and infect specific tissues; these infected cells and tissues then undergo fundamental changes at the genetic level and produce therapeutic proteins or substances, thus providing therapeutic benefits. Clinical and preclinical trials mainly utilize adeno-associated viruses (AAVs), lentiviruses (LVs), and other viruses as gene vectors for disease investigation. Although LVs have a higher gene-carrying capacity, the vector of choice for many neurological diseases is the AAV vector due to its safety and long-term transgene expression in neurons. Here, we review the basic biology of AAVs and summarize some key issues in recombinant AAV (rAAV) engineering in gene therapy research; then, we summarize recent clinical trials using rAAV treatment for neurological diseases and provide translational perspectives and future challenges on target selection.
Fabrication and Electrochemical Performance of Br-Doped Na3PS4 Solid-State Electrolyte for Sodium–Sulfur Batteries via Melt-Quenching and Hot-Pressing
Authors: Ma Ao , Liu Shuhui , Li Degui , Gu Bin , Li Sheng , Wang Jing
Published: February 2025

Room-temperature all-solid-state sodium–sulfur (Na-S) batteries are being regarded as a promising technology for large-scale energy storage. However, the low ionic conductivity of existing sulfide solid electrolytes has been hindering the potential and commercialization of Na-S batteries. Na3PS4 has garnered extensive attention among sulfide solid electrolytes due to its potential ionic conductivity (primarily predominated by vacancies) and ease of fabrication. Herein, we demonstrated a combined melt-quenching with Br doping technique to pre-generate abundant defects (vacancies) in the Na3PS4, which expanded ion transport channels and facilitated Na+ migration. The quenched Na2.9PS3.9Br0.1 holds an ionic conductivity of 8.28 × 10−4 S/cm at room temperature. Followed by the hot-pressed fabrication at 450 °C was conducted on the quenched Na2.9PS3.9Br0.1 to reduce interface resistance, the resultant Na2.9PS3.9Br0.1 pellet shows an ionic conductivity up to 1.15 × 10−3 S/cm with a wide electrochemical window and chemical stability towards Na alloy anodes. The assembled all-solid-state Na2S/Na2.9PS3.9Br0.1/Na15Sn4 cell delivers an initial reversible capacity of 550 mAh/g at a current density of 0.1 mA/cm2. After 50 cycles, it still maintains 420 mAh/g with a capacity retention of 76.4%. The integration of melt-quenching, doping, and hot-pressing provides a new strategy to enable sulfide electrolytes with high ionic conductivity and all-solid-state Na-S batteries with high performance.
Mapping the Ulcerative Colitis Patient Journey in Saudi Arabia from Healthcare Professionals’ Perspective: A Cross-Sectional Non-Interventional Study
Authors: Azzam Nahla , Mosli Mahmoud , Almutairdi Abdulelah , Alghamdi Mesfer , Meeralam Yaser , Alolimi Khalid , Arsalan Mohammad , Al-Bawardy Badr
Published: February 2025

Background/Objectives: The burden of ulcerative colitis (UC) is increasing in Saudi Arabia (KSA), and patients with UC often suffer from delays in diagnosis and appropriate management. This study investigates the current UC patient journey in KSA from the healthcare professionals’ (HCPs) perspective. It aims to evaluate treatment patterns, identify critical gaps, and provide insights to guide interventions that enhance the quality of life for UC patients in KSA. Methods: Quantitative interviews were conducted with 60 HCPs (45 gastroenterologists and 15 internal medicine specialists) from different regions in Saudi Arabia (KSA) using a Computer-Assisted Personal Interview (CAPI) system. The survey domains included clinical symptoms, diagnostic testing, endoscopic scoring, treatment goals, and medication sequencing. Results: Data were collected from 60 HCPs with an average of 17 ± 12.5 years of experience. Most patients with UC were referred by general practitioners (28%), internal medicine physicians (25%), followed by surgeons (16%). The first-ranked treatment goals were clinical remission (53.3%), endoscopic remission (35%), and improvement of quality of life (33.3%). For outpatient moderate-to-severe UC, the most common first-line treatments are oral systemic steroids (34%), 5-aminosalicylates (5-ASAs) (26%), and TNF-α inhibitors (21%). While second-line treatment rankings were TNF-α inhibitors (23%), followed by Interleukin 12/23 inhibitors (19%), and Janus kinase (JAK) inhibitors (14%). Sphingosine 1-phosphate (S1P) receptor modulators are not well-utilized due to a lack of availability (88%), unfamiliarity with the treatment (24%), and formulary exclusion (12%). Conclusions: In conclusion, most UC patients are referred by general practitioners. Treating gastroenterologists prioritize clinical remission as a treatment goal. Corticosteroids remain overutilized as reflected by treating physicians’ responses. The underutilization of advanced therapies underscores the need for enhanced education and improved access to integrate emerging therapies effectively.
Relationship Between Plasma Leptin Levels and Airflow Limitation in the Small and Medium Airways in Young Adults
Authors: Muñoz-Cofré Rodrigo , Rojas-Mancilla Edgardo , Lizana Pablo A. , Escobar-Cabello Máximo , García-Herrera Claudio , Conei Daniel , Valenzuela-Aedo Fernando , Soto-Rodríguez Francisco Javier , del Sol Mariano
Published: February 2025

Background/Objectives: To determine the relationship between plasma leptin levels and airflow limitation (AFL) in the small and medium airways of young adults according to their body composition (BC). Methods: To determine AFL, the following measurements were taken: forced expiratory volume in the first second (FEV1), forced expiratory flow between 25–75% (FEF25–75%), airway resistance (Raw), and specific airway resistance (sRaw). The measured BC variables were body mass index (BMI), body fat percentage (%BF), trunk fat percentage (TF%), and fat-free mass (FFM). Plasma leptin was measured using the ELISA technique. Results: In total, 83 participants (40 male and 43 female) aged 21.55 ± 2.08 years were evaluated. Leptin was significantly higher in women than men (p < 0.01). When relating leptin to lung function variables, FEV1 and FEF25–75% showed a significant inverse relationship (p < 0.01), and Raw and sRaw showed a direct and significant relationship (p < 0.01). Female participants with a BF% and leptin higher than their p75 were observed to have a higher risk of increased sRaw (OR = 1.0; OR = 1.15, respectively), regardless of age, and participants with an FFM% higher than their p75 had a lower risk of increased sRaw (OR = 0.71), regardless of gender and age. Conclusions: There is an inverse relationship between FEV1, FEF25–75%, and a direct relationship between Raw and sRaw with leptin. For female participants with a higher BF%, higher FFM%, and leptin, the risk of developing Raw and sRaw was found to be modified.
Plan Quality Comparison at Five Years in Two Cohorts of Breast Cancer Patients Treated with Helical Tomotherapy
Authors: Dicuonzo Samantha , Zerella Maria Alessia , Zaffaroni Mattia , Vincini Maria Giulia , Amin Karl , Ronci Giuseppe , D’arcangelo Micol , Rojas Damaris Patricia , Morra Anna , Gerardi Marianna Alessandra , Fodor Cristiana , Cambria Raffaella , Luraschi Rosa , Cattani Federica , Veronesi Paolo , De Lorenzi Francesca , Rietjens Mario , Orecchia Roberto , Leonardi Maria Cristina , Jereczek-Fossa Barbara Alicja
Published: February 2025

Objectives: this study aimed to evaluate the evolution of planned dose distribution quality in two groups of breast cancer patients treated with hypofractionated intensity-modulated radiotherapy (IMRT) using Helical TomoTherapy® at our institute 5 years apart. Methods: the analysis included two cohorts of patients who underwent implant-based immediate breast reconstruction (IBR) and received post-mastectomy IMRT to the chest wall and infra/supraclavicular lymph nodes, following a 15-fraction regimen (2.67 Gy per fraction). The first group was treated between 2012 and 2015, while the second received treatment between 2019 and 2020. Dosimetric indices derived from dose–volume histograms used in clinical practice were analyzed to assess dose distribution quality. A quantitative scoring system was applied retrospectively to compare the two groups in terms of target coverage and organ-at-risk (OAR) sparing. Additionally, capsular contracture (CC) incidence was examined in both cohorts. Results: A total of 240 patients were included in the study. The percentage of optimal treatment plans increased from 70.8% in the 2012–2015 cohort to 77.5% in the 2019–2020 cohort, while compromised plans decreased from 10.8% to 7.5%. Furthermore, the incidence of moderate-to-severe CC dropped from 54.8% in the earlier cohort to 43.5% in the later one. Conclusions: Helical Tomotherapy® has demonstrated the ability to achieve a high rate of optimal treatment plans concerning both PTV coverage and OAR sparing in a challenging population of postmastectomy patients with IBR. The learning curve showed that, after 5 years, the rate of optimal plans was increased, accompanied by a reduction in compromised plans and treatment-related toxicity.
A Bioartificial Device for the Encapsulation of Pancreatic β-Cells Using a Semipermeable Biocompatible Porous Membrane
Authors: Cuscino Nicola , Castelbuono Salvatore , Centi Claudio , Tinnirello Rosaria , Cimino Maura , Zito Giovanni , Orlando Andrea , Pinzani Massimo , Conaldi Pier Giulio , Mattina Alessandro , Miceli Vitale
Published: February 2025

Background/Objectives: Type 1 diabetes (T1D) is a chronic autoimmune condition characterized by the destruction of pancreatic β-cells, leading to insulin deficiency. Current therapies, such as islet transplantation, face significant challenges, including limited donor availability and the need for lifelong immunosuppression. Encapsulation technologies offer a promising alternative, providing immune protection and maintaining β-cell viability. In this study, we propose an encapsulation device featuring a spiral tubular semipermeable polyethersulfone (PES) membrane reinforced with a rigid biocompatible resin scaffold. Methods: The PES membrane was engineered with a tailored porosity of 0.5 µm, enabling efficient nutrient and oxygen exchange while preventing immune cell infiltration. Using INS-1E insulin-secreting cells aggregated into size-controlled islet-like spheroids (ILSs), we evaluated the device’s performance. Results: The device achieved high ILS viability and insulin secretion over 48 h at therapeutic densities, maintaining functionality comparable to free-floating ILSs (control). The PES membrane, with its mechanical stability and biocompatibility, ensured durability without compromising diffusion dynamics, overcoming a critical limitation of other encapsulation approaches. Importantly, the device geometry allowed for the encapsulation of up to 356,000 islet equivalents (IEQs) in a single capillary fiber, reaching therapeutic thresholds for T1D patients. Conclusions: this device, with its innovative design, enables high-density encapsulation while preserving ILS functionality and scalability, making it a potential platform for clinical application. This work highlights the potential of PES-based encapsulation devices to overcome key barriers in T1D treatment, paving the way for personalized, long-term solutions to restore insulin independence.
Two-Year Data on the Efficacy and Safety of the MINIject Supraciliary Implant in Patients with Medically Uncontrolled Primary Open-Angle Glaucoma
Authors: Dervenis Panagiotis , Dervenis Nikolaos , Lascaratos Gerassimos , Dimitriou Chrysostomos
Published: February 2025

Background/Objectives: The aim of this study is to evaluate the long-term efficacy and safety of the MINIject supraciliary device in patients with medically uncontrolled primary open-angle glaucoma (POAG) with up to 2 years of follow-up. Methods: A retrospective study was conducted using electronic medical records. Patients with medically uncontrolled POAG were included. Patients were either phakic, receiving combined phacoemulsification and MINIject, or pseudophakic receiving standalone MINIject. They were followed up for 24 months postoperatively. The primary outcomes were intraocular pressure (IOP) and use of IOP-lowering medications at 24 months postoperatively. Other secondary outcomes included IOP and use of glaucoma medications at 6, 12, and 18 months, success defined as 6 ≤ IOP ≤ 18 mmHg without the use of medications (complete) or regardless of the use of medications (qualified), average change in visual field (VF) mean deviation (MD) from baseline to 24 months, and adverse events. Results: The study included 37 eyes of 37 consecutive glaucoma patients. Of these, 27 underwent combined phacoemulsification with MINIject implantation and 10 had standalone MINIject. The mean preoperative IOP was 17.95 ± 4.75 mmHg on 2.16 ± 1.12 glaucoma drops. At 24 months, the mean IOP was 14.58 ± 4.55 on 0.69 ± 0.98 medications (p = 0.002). No difference in IOP was noted between the combined and the standalone group, although the latter had a trend for more glaucoma drops. The qualified success and the complete success rates were 67.6% and 56.8%, respectively. Average VF mean deviation progression was 0.19 ± 1.19 dB. No sight threatening complications occurred. Conclusions: MINIject can be a safe and effective alternative to current glaucoma devices, offering significant reduction in IOP and medication use with a good safety profile. Longer term data are needed to confirm its prolonged safety.
Comparative Safety Profiles of Biosimilars vs. Originators Used in Rheumatology: A Pharmacovigilance Analysis of the EudraVigilance Database
Authors: Nikitina Victoria , Laurini Greta Santi , Montanaro Nicola , Motola Domenico
Published: February 2025

Background: The advent of biosimilars has revolutionized the management of conditions like rheumatoid arthritis by offering cost-effective alternatives to expensive biologics. Objectives: This study aims to compare the post-marketing safety profiles of biosimilars used in rheumatology with their respective reference products (RPs). Methods: Data were retrieved from EudraVigilance for biosimilars of adalimumab, etanercept, infliximab, and rituximab, and compared with their RPs. Our analysis focused on biosimilars authorized before 2021, using data from January 2021 to December 2023. We conducted a descriptive analysis of suspected adverse events, categorized using the Medical Dictionary for Regulatory Activities, and performed a comparative analysis using the reporting odds ratio to identify potential safety signals of disproportionate reporting. Results: We analyzed 75,327 reports, identifying 566,249 drug–event pairs. The results indicate that biosimilars have safety profiles largely comparable to their RPs. Female patients predominated in the reports, representing 69.4% of RPs and 56.9% of biosimilars. Notably, biosimilars demonstrated higher reporting rates for non-serious suspected adverse drug events (AEs), such as injection site pain, arthralgia, and fatigue. Specific AEs, including drug ineffectiveness and off-label use, were more frequent for infliximab and etanercept biosimilars, possibly reflecting real-world usage patterns and nocebo effects. Serious AEs, including malignancies and immunological reactions, were also noted, underscoring the necessity for ongoing monitoring. Conclusions: Our findings suggest that biosimilars are safe alternatives to RPs, contributing to significant healthcare cost savings in the EU. This study underscores the need for ongoing pharmacovigilance and long-term safety research to validate the clinical use of biosimilars in rheumatology.
Placental Location Site and Associated Intrapartum, Postpartum, and Neonatal Complications: A Comprehensive Review and Meta-Analysis
Authors: Whitcombe Dayna D. , Hu Zhuopei , Ounpraseuth Songthip T. , Magann Everett F.
Published: February 2025

Background/Objectives: Adverse intrapartum, postpartum, and neonatal complications have been linked to placenta implantations sites. However, different reviews have led to contrasting conclusions about placental locations and pregnancy outcomes. We aim to determine if there is a relationship between the placental implantation site and intrapartum, postpartum, and neonatal outcomes. Methods: The Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines were followed during this review. The literature search used PubMed, CINAHL, and Embase. Years searched was not a study limitation. Only articles in English were included. Two authors reviewed the abstracts. Results: Of 40 articles identified as specific to intrapartum, postpartum, and/or neonatal complications (with some articles overlapping categories), 19 included intrapartum complications, 19 included postpartum complications, and 22 included neonatal complications. Pregnancies with a midline placenta (compared to a lateral placenta) had a greater likelihood of macrosomia/LGA infant (odds ratio (OR), 1.52 (95% CI: 1.22–1.90)) and lesser likelihood to have non-cephalic presentation (OR, 0.17 (95% CI: 0.06–0.51)), FGR/SGA infant (OR, 0.68 (CI: 0.55–0.85)), and retained placenta (OR, 0.33 (95% CI: 0.22–0.50)). Pregnancies with a low-lying placenta (compared to within uterine corpus) were more likely to have non-elective cesarean section (OR, 1.94 (95% CI: 1.06–3.55)) and postpartum hemorrhage (OR 1.49 (95% CI: 1.12–1.97)). Conclusions: Significant associations between placental location site and intrapartum complications (non-cephalic presentation, non-elective cesarean section), postpartum complications (postpartum hemorrhage, retained placenta), and neonatal complications (FGR/SGA, Macrosomia/LGA) were identified. There were no significant associations identified between the placental location site and several neonatal complications, including Apgar < 7 at 5 min, NICU admission, IUFD, and neonatal death.
Serum Lipids, Inflammation, and the Risk of Atrial Fibrillation: Pathophysiological Links and Clinical Evidence
Authors: Mauriello Alfredo , Correra Adriana , Maratea Anna Chiara , Caturano Alfredo , Liccardo Biagio , Perrone Marco Alfonso , Giordano Antonio , Nigro Gerardo , D’Andrea Antonello , Russo Vincenzo
Published: February 2025

Dyslipidemia is a metabolic disorder characterized by quantitative and/or qualitative abnormalities in serum lipid levels. Elevated serum cholesterol levels can modify the turnover and recruitment of ionic channels in myocytes and cellular homeostasis, including those of inflammatory cells. Experimental and clinical data indicate that inflammation is implicated in the pathophysiology of atrial remodeling, which is the substrate of atrial fibrillation (AF). Data about the association between increased lipid serum levels and AF are few and contrasting. Lipoprotein (a), adiposity, and inflammation seem to be the main drivers of AF; in contrast, low-density lipoproteins, high-density lipoproteins and triglycerides are not directly involved in AF onset. The present review aimed to describe the pathophysiological link between dyslipidemia and AF, the efficacy of lipid-lowering therapies in atherosclerotic cardiovascular disease (ASCVD) patients with and without AF, and the impact of lipid-lowering therapies on AF incidence.
Comparison of Negative Pressure Wound Therapy Systems and Conventional Non-Pressure Dressings on Surgical Site Infection Rate After Stoma Reversal: Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Anestiadou Elissavet , Stamiris Stavros , Ioannidis Orestis , Symeonidis Savvas , Bitsianis Stefanos , Bougioukas Konstantinos , Karagiannis Thomas , Kotidis Efstathios , Pramateftakis Manousos-Georgios , Mantzoros Ioannis , Cheva Angeliki , Geropoulos Georgios , Chatzianestiadou Christiana , Kaprianou Magdalini , Tserkezidis Freiderikos , Angelopoulos Stamatios
Published: February 2025

Background/Objectives: Surgical Site Infections (SSIs) rank among the most common complications following stoma takedown and lead to increased morbidity, increased Length of Hospital Stay (LOS), and higher healthcare costs. Negative Pressure Wound Therapy (NPWT) systems have emerged as a promising option for optimizing wound management and minimizing SSI rates. This systematic review and meta-analysis compares postoperative outcomes of NPWT and conventional Non-Pressure Dressings following stoma reversal. Methods: A search of the literature published up to 1 September 2024 was conducted across MEDLINE/PubMed, and the Cochrane Central Register of Controlled Trials (CENTRAL), and Scopus, as well as ClinicalTrials.gov. Only Randomized Controlled Trials (RCTs) were included. The primary outcome was SSI rate, while secondary outcomes included time to complete wound healing, LOS, and patient-reported wound cosmesis. Quality assessment was performed using the Cochrane Risk of Bias 2 (RoB 2) tool. The results were synthesized using means and Standard Deviations for continuous variables, counts and percentages for categorical variables, and presented as Odds Ratios (OR) or Mean Differences (MD) with 95% Confidence Intervals, using random or fixed effects models based on heterogeneity (I2). Results: Six RCTs, including 328 patients, were ultimately eligible for inclusion. No significant difference was revealed in SSI rates between the NPWT and conventional dressing groups (OR = 0.95; 95% CI: 0.27–3.29; p = 0.94; I2 = 38%). Time to complete wound healing was significantly lower in the NPWT group compared to conventional dressings (MD = −3.78 days; 95% CI: −6.29 to −1.27; p = 0.003). Two studies reported a lower rate of wound healing complications other than SSIs in the NPWT group (OR = 0.22; 95% CI: 0.05–1.09; p = 0.06). No substantial differences were observed in terms of LOS (MD = −0.02 days; 95% CI: −1.22 to 1.17; p = 0.97) and patient-reported wound cosmesis (SMD = 0.31; 95% CI: −0.49 to 1.11; p = 0.44). The review’s limitations include potential risk of bias, variability in study designs, and heterogeneity between studies. Conclusions: NPWT contributes to improved wound management through reducing wound healing time compared to Non-Pressure Dressings after stoma reversal, although it does not appear to substantially impact SSI rates, LOS, or patient-assessed wound cosmesis. Further large-scale, multicenter RCTs are necessary to validate these results and identify patient populations most likely to benefit from NPWT application.
Therapeutic Exercise Prescription for Overhead Athletes with Shoulder Impingement Syndrome: A Systematic Review and CERT Analysis
Authors: Guérineau Fabien , Sosa-Reina María Dolores , Almazán-Polo Jaime , Bailón-Cerezo Javier , González-de-la-Flor Ángel
Published: February 2025

Background: Shoulder impingement syndrome (SIS) is a prevalent condition among overhead athletes, often managed through therapeutic exercise interventions. However, the quality of reporting in exercise protocols significantly impacts their reproducibility and clinical implementation. The Consensus for Exercise Reporting Template (CERT) provides a standardized framework to assess the quality of exercise reporting in clinical research. Objectives: This systematic review aimed to evaluate the quality of exercise protocols used to treat SIS in overhead athletes by applying the CERT checklist. Additionally, the risk of bias was assessed to determine the methodological rigor of included studies. Methods: A systematic review was conducted following PRISMA guidelines. Six electronic databases (MEDLINE, CINAHL, Sport Discuss, Web of Science, and Cochrane) were searched for eligible studies. Inclusion criteria encompassed randomized controlled trials (RCTs), cohort studies, and case series that investigated exercise therapy for SIS in overhead athletes. Studies had to be published in English and provide details on exercise interventions. Exclusion criteria included non-human studies, acute injuries, and postoperative management. The primary outcome was the quality of intervention reporting, assessed using the CERT checklist. The secondary outcome was the risk of bias, evaluated using the modified Downs and Black checklist. Results: Five studies met the inclusion criteria, comprising four RCTs and one case series. CERT scores ranged from 6 to 13 (median = 8, IQR = 1), indicating suboptimal reporting quality. Commonly reported CERT items included equipment usage and exercise tailoring. However, key aspects such as adherence, motivation, and intervention fidelity were consistently underreported. None of the included studies provided comprehensive details on exercise interventions as per CERT guidelines, limiting their reproducibility and clinical application. Conclusions: The quality of reporting on exercise-based interventions for SIS in overhead athletes remains insufficient. Critical gaps in adherence monitoring, patient motivation, and intervention fidelity were identified. Future research should prioritize standardized and detailed reporting of exercise interventions to enhance reproducibility and facilitate evidence-based clinical practice.
Potential Impact of Choline Alphoscerate on Depressive Symptoms in Association with Insulin Resistance in Elderly Patients with Type 2 Diabetes
Authors: Lee Inkuk , Lee Minyoung , Yu Min Heui , Han Eugene , Lee Yong-ho , Lee Byung-Wan , Kang Eun Seok , Cha Bong-Soo
Published: February 2025

Background/Objectives: The aim of this study was to investigate whether Gliatamin (choline alphoscerate), an acetylcholine precursor originally used to treat dementia, improves depressive symptoms in patients with type 2 diabetes. Methods: We conducted a 6-month double-blind, randomized, and placebo-controlled trial involving 49 participants with type 2 diabetes, older than 50 years, and with mild depressive symptoms; 33 and 16 participants received choline alphoscerate (800 mg/day) and a placebo, respectively. Results: At 6 months, the Hamilton Depression Rating Scale was significantly decreased in both the choline alphoscerate (15.9 ± 6.5 to 12.6 ± 5.8, p = 0.001) and placebo (15.4 ± 4.7 to 10.2 ± 3.9, p = 0.004) groups compared with baseline, without inter-group difference (p = 0.297). Meanwhile, the choline alphoscerate group showed favorable results in insulin resistance-related parameters at 6 months, including the waist circumference (WC) and the low-density lipoprotein cholesterol (LDL)/high-density lipoprotein cholesterol (HDL) ratio (p for inter-group difference vs. placebo = 0.009 and 0.092). Even after adjusting for multiple confounding factors, choline alphoscerate use was associated with an increased odds for reduction in WC (OR 18.28 [95% CI 2.27–461.35]) and a decreased odds for a high LDL/HDL ratio at 6 months (OR 0.16 [95% CI 0.03–0.76]). Conclusions: Choline alphoscerate did not show superiority over the placebo in terms of the alleviation of depressive symptoms, despite significant pre-post changes observed within the choline alphoscerate group. Nevertheless, given its positive potential for insulin resistance, the effects of choline alphoscerate on depressive mood in relation to insulin resistance in patients with type 2 diabetes require further validation.