Biosaf Health. 2023 Dec 31;6(1):12-20. doi: 10.1016/j.bsheal.2023.12.006. eCollection 2024 Feb.

ABSTRACT

The coronavirus disease of 2019 (COVID-19), a global pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can result in severe health complications. In addition to physical preventative measures, pharmaceutical intervention is also crucial. Numerous natural products from medicinal fungi have shown promise as potential antiviral drugs and may serve as a source of effective components with antiviral activity against SARS-CoV-2 and other coronaviruses. In this study, we developed a workflow that integrates viral infection inhibition assays at both cellular and molecular levels, as well as molecular separation and characterization, to screen and identify natural products with antiviral activity. Using this workflow, we screened 167 extracts extracted from 36 medicinal fungi using optimized extraction methods. We assessed the antiviral effects of these extracts by measuring their ability to inhibit SARS-CoV-2 infection and receptor binding domain - human angiotensin-converting enzyme 2 (RBD-hACE2) binding in vitro. Following charge- and size-based characterization of the active compounds through filtration and chromatographic fractionation, mass spectrometry characterization of the fractionated compounds revealed that the active components are polysaccharides and determined their monosaccharide residue composition. Our findings provide new insights into the antiviral potential of natural products and their screening strategies and may contribute to the development of effective antiviral therapeutics against COVID-19 and other diseases.

PMID:40078308 | PMC:PMC11894996 | DOI:10.1016/j.bsheal.2023.12.006

Philos Trans A Math Phys Eng Sci. 2025 Mar 13;383(2292):20240228. doi: 10.1098/rsta.2024.0228. Epub 2025 Mar 13.

ABSTRACT

The objective of precision medicine is to tailor interventions to an individual patient's unique characteristics. A key technology for this purpose involves medical digital twins, computational models of human biology that can be personalized and dynamically updated to incorporate patient-specific data. Certain aspects of human biology, such as the immune system, are not easily captured with physics-based models, such as differential equations. Instead, they are often multi-scale, stochastic and hybrid. This poses a challenge to existing control and optimization approaches that cannot be readily applied to such models. Recent advances in neural-network control methods hold promise in addressing complex control problems. However, the application of these approaches to biomedical systems is still in its early stages. This work employs dynamics-informed neural-network controllers as an alternative approach to control of medical digital twins. As a first use case, we focus on the control of agent-based models (ABMs), a versatile and increasingly common modelling platform in biomedicine. The effectiveness of the proposed neural-network control methods is illustrated and benchmarked against other methods with two widely used ABMs. To account for the inherent stochastic nature of the ABMs we aim to control, we quantify uncertainty in relevant model and control parameters.This article is part of the theme issue 'Uncertainty quantification for healthcare and biological systems (Part 1)'.

PMID:40078154 | DOI:10.1098/rsta.2024.0228

J Physiol. 2025 Mar 12. doi: 10.1113/JP287595. Online ahead of print.

ABSTRACT

The intrinsic cardiac nervous system (ICNS), termed as the heart's 'little brain', is the final point of neural regulation of cardiac function. Studying the dynamic behaviour of these ICNS neurons via multiscale neuronal computer models has been limited by the sparsity of electrophysiological data. We developed and analysed a computational library of neuronal electrophysiological models based on single neuron transcriptomic data obtained from ICNS neurons. Each neuronal genotype was characterized by a unique combination of ion channels identified from the transcriptomic data, using a cycle threshold cutoff that ensured the electrical excitability of the neuronal models. The parameters of the ion channel models were grounded based on passive properties (resting membrane potential, input impedance and rheobase) to avoid biasing the dynamic behaviour of the model. Consistent with experimental observations, the emergent model dynamics showed phasic activity in response to the current clamp stimulus in a majority of neuronal genotypes (61%). Additionally, 24% of the ICNS neurons showed a tonic response, 11% were phasic-to-tonic with increasing current stimulation and 3% showed tonic-to-phasic behaviour. The computational approach and the library of models bridge the gap between widely available molecular-level gene expression and sparse cellular-level electrophysiology for studying the functional role of the ICNS in cardiac regulation and pathology. KEY POINTS: Computational models were developed of neuron electrophysiology from single-cell transcriptomic data from neurons in the heart's 'little brain': the intrinsic cardiac nervous system. The single-cell transcriptomic data were thresholded to select the ion channel combinations in each neuronal model. The library of neuronal models was constrained by the passive electrical properties of the neurons and predicted a distribution of phasic and tonic responses that aligns with experimental observations. The ratios of model-predicted conductance values are correlated with the gene expression ratios from transcriptomic data. These neuron models are a first step towards connecting single-cell transcriptomic data to dynamic, predictive physiology-based models.

PMID:40077928 | DOI:10.1113/JP287595

Nutrients. 2025 Feb 27;17(5):815. doi: 10.3390/nu17050815.

ABSTRACT

Background/Objectives: Post-menopausal women are at an increased risk of developing cardiovascular disease. Menaquinone-7 (MK-7) is a fat-soluble vitamin involved in coagulation and maintaining vascular health. The aim of the post hoc analysis of this one-year study is to investigate the effects of MK-7 supplementation on the vascular parameters in pre-, peri-, and post-menopausal women. Methods: In a clinical intervention trial (NCT02404519), a total of 165 women with a low vitamin K status received either 180 µg of MK-7 daily (n = 82) or a matching placebo (n = 83) for one year. Established vascular parameters were measured before and after one year of vitamin K2 supplementation. Pre-, peri-, and post-menopausal women were subdivided according to arterial stiffness, with a high b-stiffness index defined as being greater than the overall median of 9.83. Results: The post hoc analyses showed a significant decrease in desphospho-uncarboxylated matrix Gla protein (dp-ucMGP) plasma levels after MK-7 supplementation (pre/peri, p = 0.009; post, p < 0.001). MK-7 treatment significantly attenuated vascular stiffness in post-menopausal women (placebo +49.1% ± 77.4; MK-7 +9.4% ± 67.1; p = 0.035). Post-menopausal women with a high stiffness index showed significantly improved vascular markers after MK-7 treatment, e.g., a decreased blood pressure at brachialis (-3.0% ± 9.0; p = 0.007) and an increased distensibility coefficient (+13.3% ± 32.3; p = 0.040). Conclusions: Our results confirm that menopause affects vascular health status. Post-menopausal women with an increased stiffness benefit most from MK-7 supplementation, with a significantly improved blood pressure. Further research is needed to unravel the beneficial effects of MK-7 in post-menopausal women.

PMID:40077685 | DOI:10.3390/nu17050815

Int J Mol Sci. 2025 Mar 5;26(5):2311. doi: 10.3390/ijms26052311.

ABSTRACT

T cells play diverse roles in cancer immunology, acting as tumor suppressors, cytotoxic effectors, enhancers of cytotoxic T lymphocyte responses and immune suppressors; providing memory and surveillance; modulating the tumor microenvironment (TME); or activating innate immune cells. However, cancer cells can disrupt T cell function, leading to T cell exhaustion and a weakened immune response against the tumor. The expression of exhausted T cell (Tex) markers plays a pivotal role in shaping the immune landscape of multiple cancers. Our aim was to systematically investigate the role of known T cell exhaustion (Tex) markers across multiple cancers while exploring their molecular interactions, mutation profiles, and potential implications for immunotherapy. The mRNA expression profile of six Tex markers, LAG-3, PDCD1, TIGIT, HAVCR2, CXCL13, and LAYN was investigated in pan-cancer. Utilizing data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), The Cancer Proteome Atlas (TCPA), and other repositories, we characterized the differential expression of the Tex markers, their association with the patients' survival outcome, and their mutation profile in multiple cancers. Additionally, we analyzed the effects on cancer-related pathways and immune infiltration within the TME, offering valuable insights into mechanisms of cancer immune evasion and progression. Finally, the correlation between their expression and sensitivity to multiple anti-cancer drugs was investigated extensively. Differential expression of all six markers was significantly associated with KIRC and poor prognosis in several cancers. They also played a potential activating role in apoptosis, EMT, and hormone ER pathways, as well as a potential inhibitory role in the DNA damage response and RTK oncogenic pathways. Infiltration of different immune cells was also found to be associated with the expression of the Tex-related genes in most cancer types. These findings underline that the reviving of exhausted T cells can be used to enhance the efficacy of immunotherapy in cancer patients.

PMID:40076932 | DOI:10.3390/ijms26052311

Int J Mol Sci. 2025 Feb 28;26(5):2224. doi: 10.3390/ijms26052224.

ABSTRACT

Three-dimensional genome organization reveals that gene regulatory elements, which are linearly distant on the genome, can spatially interact with target genes to regulate their expression. DNA fluorescence in situ hybridization (DNA-FISH) is an efficient method for studying the spatial proximity of genomic loci. In this study, we developed an optimized Tn5 transposome-based DNA-FISH method, termed Tn5-labeled DNA-FISH. This approach amplifies the target region and uses a self-assembled Tn5 transposome to simultaneously fragment the DNA into ~100 bp segments and label it with fluorescent oligonucleotides in a single step. This method enables the preparation of probes for regions as small as 4 kb and visualizes both endogenous and exogenous genomic loci at kb resolution. Tn5-labeled DNA-FISH provides a streamlined and cost-effective tool for probe generation, facilitating the investigation of chromatin spatial conformations, gene interactions, and genome architecture.

PMID:40076846 | DOI:10.3390/ijms26052224

Int J Mol Sci. 2025 Feb 28;26(5):2196. doi: 10.3390/ijms26052196.

ABSTRACT

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.

PMID:40076813 | DOI:10.3390/ijms26052196

Int J Mol Sci. 2025 Feb 27;26(5):2078. doi: 10.3390/ijms26052078.

ABSTRACT

Autism spectrum disorder (ASD) is a complex multifactorial neurodevelopmental disorder. Despite extensive research involving genome-wide association studies, copy number variant (CNV) testing, and genome sequencing, the comprehensive genetic landscape remains incomplete. In this context, we developed a systems biology approach to prioritize genes associated with ASD and uncover potential new candidates. A Protein-Protein Interaction (PPI) network was generated from genes associated to ASD in a public database. Leveraging gene topological properties, particularly betweenness centrality, we prioritized genes and unveiled potential novel candidates (e.g., CDC5L, RYBP, and MEOX2). To test this approach, a list of genes within CNVs of unknown significance, identified through array comparative genomic hybridization analysis in 135 ASD patients, was mapped onto the PPI network. A prioritized gene list was obtained through ranking by betweenness centrality score. Intriguingly, by over-representation analysis, significant enrichments emerged in pathways not strictly linked to ASD, including ubiquitin-mediated proteolysis and cannabinoid receptor signaling, suggesting their potential perturbation in ASD. Our systems biology approach provides a promising strategy for identifying ASD risk genes, especially in large and noisy datasets, and contributes to a deeper understanding of the disorder's complex genetic basis.

PMID:40076702 | DOI:10.3390/ijms26052078

Int J Mol Sci. 2025 Feb 21;26(5):1861. doi: 10.3390/ijms26051861.

ABSTRACT

Integrin-linked kinase (ILK) is a key scaffolding protein between extracellular matrix protein and the cytoskeleton and has been implicated previously in the pathogenesis of renal damage. However, its involvement in renal mitochondrial dysfunction remains to be elucidated. We studied the role of ILK and its downstream regulations in renal damage and mitochondria function both in vivo and vitro, using a folic acid (FA)-induced kidney disease model. Wild type (WT) and ILK conditional-knockdown (cKD-ILK) mice were injected with a single intraperitoneal dose of FA and studied after 15 days of chronic renal damage progression. Human Kidney tubular epithelial cells (HK2) were transfected with specific siRNAs targeting ILK, glycogen synthase kinase 3-β (GSK3β), or CCAAT/enhancer binding protein-β (C/EBPβ). The expressions and activities of renal ILK, GSK3β, C/EBPβ, mitochondrial oxidative phosphorylation enzymes, and mitochondrial membrane potential were assessed. Additionally, the expression of markers for fibrosis fibronectin (FN) and collagen 1 (COL1A1), for autophagy p62 and cytosolic light chain 3 (LC3B) isoforms II and I, and mitochondrial homeostasis marker carnitine palmitoyl-transferase 1A (CPT1A) were evaluated using immunoblotting, RT-qPCR, immunofluorescence, or colorimetric assays. FA upregulated ILK expression, leading to the decrease of GSK3β activity, increased tubular fibrosis, and produced mitochondrial dysfunction, both in vivo and vitro. These alterations were fully or partially reversed upon ILK depletion, mitigating FA-induced renal damage. The signaling axis composed by ILK, GSK3β, and C/EBPβ regulated CPT1A transcription as the limiting factor in the FA-based impaired mitochondrial activity. We highlight ILK as a potential therapeutical target for preserving mitochondrial function in kidney injury.

PMID:40076489 | DOI:10.3390/ijms26051861

Int J Mol Sci. 2025 Feb 21;26(5):1854. doi: 10.3390/ijms26051854.

ABSTRACT

In recent years, the emergence of insecticide resistance has been a major challenge to global public health. Understanding the molecular mechanisms of this phenomenon in mosquito vectors is paramount for the formulation of effective vector control strategies. This review explores the current knowledge of insecticide resistance mechanisms through omics approaches. Genomic, transcriptomic, proteomic, and metabolomics approaches have proven crucial to understand these resilient vectors. Genomic studies have identified multiple genes associated with insecticide resistance, while transcriptomics has revealed dynamic gene expression patterns in response to insecticide exposure and other environmental stimuli. Proteomics and metabolomics offer insights into protein expression and metabolic pathways involved in detoxification and resistance. Integrating omics data holds immense potential to expand our knowledge on the molecular basis of insecticide resistance in mosquitoes via information obtained from different omics platforms to understand regulatory mechanisms and differential expression of genes and protein, and to identify the transcription factors and novel molecules involved in the detoxification of insecticides. Eventually, these data will help construct predictive models, identify novel strategies, and develop targeted interventions to control vector-borne diseases.

PMID:40076478 | DOI:10.3390/ijms26051854

Nat Commun. 2025 Mar 12;16(1):2479. doi: 10.1038/s41467-025-56628-w.

ABSTRACT

Predicting and quantifying phenotypic consequences of genetic variants in rare disorders is a major challenge, particularly pertinent for 'actionable' genes such as thyroid hormone transporter MCT8 (encoded by the X-linked SLC16A2 gene), where loss-of-function (LoF) variants cause a rare neurodevelopmental and (treatable) metabolic disorder in males. The combination of deep phenotyping data with functional and computational tests and with outcomes in population cohorts, enabled us to: (i) identify the genetic aetiology of divergent clinical phenotypes of MCT8 deficiency with genotype-phenotype relationships present across survival and 24 out of 32 disease features; (ii) demonstrate a mild phenocopy in ~400,000 individuals with common genetic variants in MCT8; (iii) assess therapeutic effectiveness, which did not differ among LoF-categories; (iv) advance structural insights in normal and mutated MCT8 by delineating seven critical functional domains; (v) create a pathogenicity-severity MCT8 variant classifier that accurately predicted pathogenicity (AUC:0.91) and severity (AUC:0.86) for 8151 variants. Our information-dense mapping provides a generalizable approach to advance multiple dimensions of rare genetic disorders.

PMID:40075072 | DOI:10.1038/s41467-025-56628-w

Semin Ophthalmol. 2025 Mar 13:1-7. doi: 10.1080/08820538.2025.2467853. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate and contrast the effectiveness and safety of two conbercept treatment protocols-a three-dose treat-and-extend (3+T&E) regimen and a three-dose pro re nata (3+PRN) regimen-in Chinese patients diagnosed with neovascular age-related macular degeneration (nAMD).

METHODS: Eligible patients, who had not undergone anti-VEGF intraocular injections within 3 months prior to enrollment, were randomly assigned to either the 3+T&E or 3+PRN regimen. The 3+T&E group received at least three monthly injections, with subsequent visit intervals extended based on disease activity assessment. The primary endpoint was the mean change in best-corrected visual acuity (BCVA) from baseline to week 48, using a predefined noninferiority threshold.

RESULTS: Among 501 participants (249 in 3+T&E, 252 in 3+PRN), approximately half had prior anti-VEGF treatment. At 48 weeks, both regimens showed significant BCVA improvements (+9.9 for 3+PRN, +8.6 for 3+T&E; p = .208), with comparable rates of ≥15-letter gains (32.12% for 3+PRN, 30.77% for 3+T&E; p = .827). The 3+PRN group received fewer injections (mean 6.4 vs. 6.9 in 3+T&E; p = .028) but had shorter intervals between injections (6.93 weeks vs. 7.46 weeks in 3+T&E; p = .010). Drug-related adverse events occurred in 5% of patients, with ocular events evenly distributed and minimal cardiovascular events reported.

CONCLUSION: Both 3+T&E and 3+PRN conbercept regimens effectively improved visual and anatomical outcomes in Chinese nAMD patients. The 3+T&E regimen was noninferior to 3+PRN in improving BCVA from baseline to week 48. The 3+T&E regimen enabled longer injection intervals while 3+PRN regimen with less injections is more cost-effective while maintaining a comparable safety profile. Treatment plan tailored to an individual patient's situation appears necessary.

PMID:40079155 | DOI:10.1080/08820538.2025.2467853

Anesth Pain Med. 2024 Sep 8;14(4):e148739. doi: 10.5812/aapm-148739. eCollection 2024 Aug.

ABSTRACT

BACKGROUND: This study compares the effects of transforaminal magnesium sulfate injection versus other methods for managing radicular back pain, highlighting its potential for improved pain relief and functional outcomes.

METHODS: This randomized, double-blind clinical trial involved 30 patients with radicular back pain who were randomly assigned to receive either transforaminal magnesium sulfate or triamcinolone injection. Primary outcomes were pain intensity and functional disability, assessed using the Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI), respectively. These were evaluated at five time points: Before the injection, 2 weeks, 1 month, 3 months, and 6 months after the injection. Secondary outcomes included drug-related adverse events within the six-month follow-up period.

RESULTS: Baseline characteristics were not significantly different between the two study groups. Compared to pre-injection measures, post-injection pain intensity and functional disability were significantly reduced in both groups at all time points (P < 0.001). At all postoperative evaluations, pain intensity and functional disability were lower in the magnesium sulfate group compared to the steroid group (P < 0.001). No drug-related side effects were recorded in either group.

CONCLUSIONS: For patients with radicular back pain, transforaminal magnesium sulfate injection appears to be an effective and safe alternative to transforaminal steroid injection.

PMID:40078471 | PMC:PMC11895787 | DOI:10.5812/aapm-148739

Front Pharmacol. 2025 Feb 26;16:1522543. doi: 10.3389/fphar.2025.1522543. eCollection 2025.

ABSTRACT

OBJECTIVE: This study aimed to evaluate the efficacy and safety of antiepileptic drugs and non-pharmacological treatments in patients with Lennox-Gastaut syndrome (LGS).

METHODS: We conducted a systematic search of the PubMed, Embase, Cochrane, and Web of Science databases for randomized controlled trials (RCTs) evaluating both pharmacological and non-pharmacological interventions for LGS. The treatments assessed included cannabidiol, fenfluramine, clobazam, rufinamide, felbamate, lamotrigine, topiramate, deep brain stimulation, and anterior corpus callosotomy. The primary efficacy outcome was defined as a reduction of at least 50% in the frequency of drop seizures during treatment compared to baseline levels. The secondary efficacy outcome was measured as the median percentage reduction in monthly drop seizure frequency throughout the treatment period. Safety assessments were based on the incidence of adverse events and serious adverse events. All outcomes were ranked according to their surface under the cumulative ranking curve (SUCRA).

RESULT: This network meta-analysis encompassed 12 RCTs involving a total of 1,445 patients. The SUCRA indicated that clobazam 1 mg/kg/day, anterior corpus callosotomy, and rufinamide were the three most effective interventions for achieving a reduction of at least 50% in drop seizures. In terms of median percentage reduction in drop seizure frequency, clobazam 1 mg/kg/day ranked highest, followed by clobazam 0.5 mg/kg/day and rufinamide. Regarding safety profiles, SUCRA analysis revealed that cannabidiol 20 mg/kg/day had the highest likelihood of inducing adverse events, followed closely by fenfluramine 0.7 mg/kg/day. Lamotrigine was found to be most likely to cause serious adverse reactions, with cannabidiol 10 mg/kg/day following closely behind.

CONCLUSION: Clobazam 1 mg/kg/day, anterior corpus callosotomy, and rufinamide manifested the most optimal efficacy in seizure control among LGS patients. Caution should be exercised when administering cannabidiol, lamotrigine, and fenfluramine 0.7 mg/kg/day in clinical practice to mitigate safety concerns associated with drug-related side effects.

PMID:40078280 | PMC:PMC11898213 | DOI:10.3389/fphar.2025.1522543

Front Oncol. 2025 Feb 26;15:1507281. doi: 10.3389/fonc.2025.1507281. eCollection 2025.

ABSTRACT

Pulmonary arterial intimal sarcoma (PAIS) is a rare malignant mesenchymal tumor often associated with an unfavorable prognosis and lacks a standardized treatment approach to date. This report presents a notable case of PAIS treated with neoadjuvant therapy involving anlotinib concomitantly administered with chemotherapy of ifosfamide and pirarubicin, which resulted in a favorable outcome. A 38-year-old man was admitted to our hospital with chest tightness, cough, and dyspnea, all of which had persisted for more than a week. Initial evaluation via chest computed tomography (CT) revealed a sizable posterior mediastinal tumor measuring 11.9 × 7.6 cm. A CT-guided biopsy was performed, and pathological findings confirmed the diagnosis of PAIS. Efficacy evaluation showed slow progress after one cycle of chemotherapy with ifosfamide and pirarubicin. To enhance treatment outcomes, we incorporated anlotinib as a neoadjuvant therapy alongside ifosfamide and pirarubicin. Subsequent CT imaging demonstrated a significant reduction in tumor size, and the patient experienced notable alleviation of symptoms. The patient then underwent surgery, radiation, and subsequently, maintenance treatment with anlotinib for one year. No severe drug-related side effects were observed. The patient achieved progression-free survival of 25 months following administration of anlotinib. Thus, the combination of anlotinib with ifosfamide and pirarubicin demonstrated significant efficacy and safety. This approach holds promise as an effective therapeutic strategy for managing unresectable, locally advanced, or advanced PAIS. However, further clinical studies are necessary to validate these findings.

PMID:40078190 | PMC:PMC11897571 | DOI:10.3389/fonc.2025.1507281

Diagnostics (Basel). 2025 Mar 4;15(5):619. doi: 10.3390/diagnostics15050619.

ABSTRACT

Background: Prolonged courses of glucocorticoids (GCs) for patients suffering from inflammatory rheumatic diseases (IRDs) are associated with adverse effects. High-frequency ultrasonography (HFUS) has been utilized to quantify skin changes during short-term topical GC treatment. We aimed to quantify skin atrophy in IRD patients treated systemically with prolonged courses of GCs. Methods: We performed a cross-sectional study comparing patients with IRDs and GC treatment who presented with clinically evident skin atrophy to a matched cohort (1:1) without IRDs and GC treatment. Skinfold measurements, utilizing a standardized caliper, and B-mode HFUS images, utilizing an 18 MHz linear sonography probe, were acquired at back-of-hand, cubital, and dorsal midfoot regions and then compared between both groups. Results: A total of 53 GC-treated IRD patients (33 (62%) women, mean age 66.4 (±10.0) years, GC treatment median 8.0 (1.0-47.0) years) were compared to 53 subjects without IRDs and GC treatment (32 (60%) women, 65.9 (±11.3) years). Skinfold thickness measured at the back of hands [1.7 (±0.4) vs. 2.1 (±0.5) mm, p < 0.001], but not at the cubital [6.7 (±2.7) vs. 7.1 (±3.0) mm] or dorsal midfoot [3.6 (±3.7) vs. 4.1 (±3.4) mm] areas, showed a significant difference between the groups. In comparison, all areas displayed statistically significant different cutaneous thickness in the evaluation by HFUS: hand 0.66 (±0.12) vs. 0.82 (±0.18), p < 0.001; cubital 0.86 (±0.15) vs. 1.00 (±0.21), p < 0.001; and midfoot 0.76 (±0.16) vs. 0.94 (±0.18), p < 0.001. Conclusions: This study revealed significantly lower values in the measured cutaneous thickness by HFUS for GC-treated patients with IRDs compared to persons without IRD and GC treatment.

PMID:40075866 | DOI:10.3390/diagnostics15050619

Pediatr Rheumatol Online J. 2025 Mar 12;23(1):26. doi: 10.1186/s12969-025-01074-7.

ABSTRACT

INTRODUCTION: Mycophenolate Mofetil (MMF) has become one of the cornerstone treatments of lupus nephritis (LN). It is converted into mycophenolic acid (MPA), an active metabolite, that displays high inter- and intra-individual pharmacokinetic variability. However, the routine monitoring of MPA trough level is still debatable.

OBJECTIVES: The present study aims to evaluate the relationship between MPA trough levels and both clinical outcomes and drug-related adverse effects during the maintenance phase of LN in Egyptian patients.

METHODS: We included thirty-five adults and twenty-nine children with biopsy-proven class III and IV LN, who had been maintained on steroid and MMF as maintenance therapy for more than six months. Clinical and laboratory markers of lupus activity as well as MMF adverse events were reported. MPA trough levels were measured by High-Performance Liquid Chromatography (HPLC).

RESULTS: There was a significant association between low MPA trough levels and both flares and SLEDAI scores in the adult group (P = 0.027 and 0.019, respectively). Moreover, high MPA trough levels were associated with higher risk of gastritis in the same age group (P = 0.007). There was no significant association with any of the parameters studied in the pediatric group. Gastritis was the most frequent side effect in both age groups.

CONCLUSION: MPA trough levels correlated with disease activity and gastritis in adult LN patients, and this may help to optimize MMF dosage in these patients. However, MPA concentration-effect relationships were not observed in pediatric patients.

PMID:40075510 | DOI:10.1186/s12969-025-01074-7

Sci Rep. 2025 Mar 12;15(1):8597. doi: 10.1038/s41598-025-92330-z.

ABSTRACT

This study aims to explore potential adverse events (AEs) related to Dupilumab using data from the US FDA Adverse Event Reporting System (FAERS) database. The FAERS database from Q2 2017 to Q4 2023 was mined for AEs related to Dupilumab. The types of AEs reported, along with gender, age distribution, and severity, were evaluated. Signal detection methods including Reporting Odds Ratio, Proportional Reporting Ratio, Bayesian Confidence Propagation Neural Network, and Empirical Bayesian Geometric Mean were used. A total of 11,547,571 AE reports were collected, with 5335 reports suspected of being related to Dupilumab, identifying 307 Preferred Terms involving 27 System Organ Classes. Reports from female patients outnumbered males (56.08% vs. 34.65%). Patients aged 45-65 years reported the most events (21.34%). The number of reports increased significantly in 2023 (34.25%) compared to 2017 (0.42%), with the highest reporting rate from the US (98.07%). Common AEs included Pruritus, Product use in unapproved indication, and Rash, with Product dose omission issue indicating widespread misuse of Dupilumab. High signal strength AEs included Rebound atopic dermatitis, Rebound eczema, Dermatitis atopic, and Dry skin; injection site AEs like Injection site dryness and eczema; new potential AEs such as Dry eye, Eye pruritus, Ocular hyperaemia, Eye irritation, Conjunctivitis, Vision blurred, and Sleep disorder. This study reveals various potential AEs associated with Dupilumab, including newly identified risks. Future research needs to delve deeper into the safety of Dupilumab to better guide its clinical application.

PMID:40074775 | DOI:10.1038/s41598-025-92330-z

Daru. 2025 Mar 12;33(1):13. doi: 10.1007/s40199-025-00559-w.

ABSTRACT

INTRODUCTION: Leukocytoclastic vasculitis (LCV) is a small-vessel inflammatory condition that can rarely occur as an adverse drug reaction (ADR). Vancomycin-induced LCV is an uncommon but potentially serious complication, particularly in patients with pre-existing renal impairment.

REASON FOR THE REPORT: This case report describes a patient with end-stage renal disease (ESRD) who developed LCV following vancomycin therapy for a catheter-related infection. The report emphasizes the diagnostic challenges and the importance of prompt and appropriate management of this ADR. A 53-year-old male with ESRD developed skin lesions and systemic symptoms after receiving vancomycin for catheter-related infection. The diagnosis of LCV was confirmed through a skin biopsy. Discontinuation of vancomycin with initiation of mycophenolate mofetil and prednisolone resulted in significant improvement in the patient's condition.

OUTCOME: The presented case underlines the recognition of vancomycin-induced LCV, especially in the vulnerable population of patients with ESRD. It emphasizes the need for a high degree of suspicion of drug-related adverse events and early diagnosis and management to achieve good outcomes.

CLINICAL TRIAL NUMBER: Not applicable.

PMID:40072667 | DOI:10.1007/s40199-025-00559-w

Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2024 Oct 28;49(10):1601-1610. doi: 10.11817/j.issn.1672-7347.2024.240109.

ABSTRACT

OBJECTIVES: Staphylococcus epidermidis (S. epidermidis) adheres to the surface of medical devices, forming highly drug-resistant biofilms, which has made the development of novel antibacterial agents against S. epidermidis and its biofilms a key research focus. By drug repurposing, this study aims to explore the combinational antimicrobial effects between pinaverium bromide (PVB), a L-type calcium channel blocker, and oxacillin (OXA) against S. epidermidis.

METHODS: Clinical isolates of S. epidermidis were collected from January to September 2022 at the Department of Clinical Laboratory of the Third Xiangya Hospital, Central South University. The minimal inhibitory concentrations (MICs) of PVB and OXA were determined using the broth microdilution method. Checkerboard assays and time-kill curves were performed to assess the fractional inhibitory concentration index and synergistic bactericidal efficiency of the drug combination. Resistance selection assays evaluated PVB's ability to inhibit the development of OXA resistance. Biofilm eradication assays, combined with confocal laser scanning microscopy (CLSM) and the persister cell quantification, were conducted to evaluate the effect of PVB and OXA on drug-resistant biofilms and persister cells. The mechanisms of PVB action were further investigated using transmission electronic microscopy (TEM), reactive oxygen species (ROS) quantification, and ATP quantification.

RESULTS: The MICs of PVB and OXA against the standard strain S. epidermidis RP62A were both 8 μg/mL. Checkerboard assays showed that the fractional inhibitory concentration index (FICI) for the combination was 0.250 0 for RP62A and ranged from 0.187 5 to 0.500 0 for clinical isolates, indicating synergistic effects. Resistance selection assays demonstrated that PVB not only failed to induce resistance but also effectively inhibited the development of OXA resistance. The combination of 1×MIC of PVB and OXA reduced biofilm biomass (A570 nm) from (2.36±0.46) to (1.12±0.39) (t=3.504, P=0.02). CLSM revealed significant biofilm structural disruption and an increased proportion of dead bacteria. Additionally, after 4 hours of treatment, the total persister cell count was reduced from lg(7.73±0.21) to lg(2.79±0.43) (t=4.143, P=0.014). Synergistic biofilm eradication was further confirmed in clinical isolates. TEM revealed that PVB caused significant bacterial structural damage. The combination of OXA and PVB significantly induced ROS production, increasing the relative fluorescence intensity from (30 000.00±2 000.00) to (45 666.67±2 081.67) (t=10.68, P<0.001), and markedly reduced ATP generation, lowering the relative fluorescence intensity form (565.00±33.18) to (205.67±35.23) (t=4.932, P=0.003).

CONCLUSIONS: The combination of PVB and OXA exhibits significant synergistic antimicrobial activity against S. epidermidis, its biofilms, and persister cells. This combination holds promise as a potential alternative therapy for biofilm-associated infections caused by S. epidermidis.

PMID:40074309 | DOI:10.11817/j.issn.1672-7347.2024.240109