Medicina (Kaunas). 2025 Feb 6;61(2):283. doi: 10.3390/medicina61020283.

ABSTRACT

Background and Objectives: The aim of our study is to compare the effects of pirfenidone and nintedanib on lung function and radiologic findings in Idiopathic Pulmonary Fibrosis and to identify which drug is more appropriate for which patient group. Materials and Methods: The data of patients who were treated in our department for at least one year between 1 January 2010 and 31 December 2022 and who were started on pirfenidone or nintedanib treatment with the diagnosis of Idiopathic Pulmonary Fibrosis were retrospectively reviewed. The patients were divided into two groups-the nintedanib and pirfenidone groups-and both groups were compared in terms of progression in lung function tests (changes in FEV1, FVC, 6 MWT and DLCO values at the 3rd, 6th, 9th and 12th months compared to baseline values) and radiological findings (the presence of progression in findings such as ground-glass opacity, reticulation, honeycomb and traction bronchiectasis) within 1 year after diagnosis. Results: The study included 109 patients. The number of patients treated with pirfenidone (IPF patients) was 82 (75.2%) and the number of patients treated with nintedanib was 27 (24.8%). When the PFT values at 3, 6, 9 and 12 months were compared with the baseline values in both groups, there was no statistically significant difference in any parameter between the two groups. No significant difference was found in terms of radiological progression at the end of 1 year in both groups. Conclusions: The results of our study show that pirfenidone and nintedanib are equivalent in their effectiveness in preventing disease progression in patients with IPF.

PMID:40005400 | DOI:10.3390/medicina61020283

Medicina (Kaunas). 2025 Jan 31;61(2):244. doi: 10.3390/medicina61020244.

ABSTRACT

Background and Objectives: Acute exacerbation of idiopathic pulmonary fibrosis (IPF-AE) often results in severe respiratory distress requiring treatment in the intensive care unit and has a high mortality rate. Identifying prognostic markers and assessing disease severity are crucial for clinicians to gain detailed insights. The mean platelet volume-to-platelet count ratio (MPR) is an inflammatory marker commonly used in malignancies. This study aimed to evaluate MPR and other factors affecting mortality in patients with IPF-AE who were monitored in the intensive care unit (ICU). Materials and Methods: This retrospective study was conducted on patients monitored in the ICU for IPF-AE between 2017 and 2023. Demographic characteristics, vital signs, laboratory and imaging findings, and administered treatments were reviewed. MPR was calculated by dividing the mean platelet volume by the platelet count. The primary endpoint was defined as 1-month in-hospital mortality. Results: A total of 59 patients monitored in the ICU for IPF-AE were included in the study. The mean age of the patients was 62.75 years, and 81.4% of the participants were male. During the 30-day follow-up period, 62.7% of the patients died. The need for invasive mechanical ventilation (IMV) was significantly associated with increased mortality (p < 0.001). The optimal cutoff value for MPR was determined to be 0.033, with a sensitivity of 83.7% and specificity of 63.64%, indicating its predictive value for mortality (AUC: 0.764; 95% CI: 0.635-0.864; p < 0.001). Conclusions: In this study, the need for IMV emerged as a critical parameter in predicting mortality in patients with IPF-AE. Additionally, the use of the MPR as a prognostic biomarker may offer a novel approach in the management of IPF patients. These findings could contribute to the development of strategies aimed at early intervention in IPF patients. Further studies with larger sample sizes are needed to validate these results. This study has demonstrated that MPR is a significant prognostic biomarker for predicting mortality in patients with IPF-AE who are managed in the intensive care unit. The potential use of MPR as a biomarker in clinical decision-making may provide new approaches to the management of IPF patients. Additionally, the need for IMV in IPF-AE emerges as a critical parameter for predicting mortality. These findings may contribute to the development of early intervention strategies for IPF patients. Further studies with larger cohorts are needed to validate these results.

PMID:40005361 | DOI:10.3390/medicina61020244

J Clin Med. 2025 Feb 17;14(4):1317. doi: 10.3390/jcm14041317.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a relatively common progressive fibrotic interstitial lung disease associated with significant morbidity and mortality. The available medications for IPF only slow down the disease process, with lung transplantation the only option for a cure. Non-pharmacological therapies are significant adjuncts that can improve symptom burden and quality of life with minimal or no side effects. Supplemental oxygen can improve exercise capacity and the sensation of dyspnea in a significant portion of patients with resting or exertional hypoxemia and has been supported by several professional societies. Pulmonary rehabilitation is a comprehensive program that includes education and therapeutic exercises to improve patient stamina and strength. It is one of the few interventions that have been shown to produce a meaningful increase in a patient's exercise capacity, but its wide adoption is limited by availability, especially in rural areas. Sleep optimization with supplemental oxygen and positive airway pressure therapy should actively be investigated for all patients diagnosed with IPF. Although gastroesophageal reflux control with non-pharmacological means is still controversial as an intervention to reduce the rate of lung function decline, it can help control reflux symptoms and improve cough intensity. IPF patients should be educated on the importance of balanced nutrition and the potential benefits of screening for lung transplantation. Palliative medicine can help with symptom control and should be considered for all patients regardless severity, but especially in those in the later stages of disease.

PMID:40004847 | DOI:10.3390/jcm14041317

J Clin Med. 2025 Feb 15;14(4):1300. doi: 10.3390/jcm14041300.

ABSTRACT

Background: Patients with idiopathic pulmonary fibrosis (IPF) have a high prevalence of cardiovascular (CV) risk factors and an increased CV disease burden. The aim of this study was to investigate the prognostic role of the ascending aorta (AA) diameter in patients with mild-to-moderate IPF and to identify the main determinants of AA dilatation. Methods: All IPF patients without severe pulmonary hypertension who underwent a multi-instrumental evaluation, comprehensive of high-resolution computed tomography (HRCT) and transthoracic echocardiography (TTE), between September 2017 and November 2023, were retrospectively analyzed. The primary endpoint was the composite of "all-cause mortality or re-hospitalization for all causes", over a medium-term follow-up. The secondary endpoint was to evaluate the independent predictors of AA dilatation. Additionally, Bland-Altman analysis was used to assess the accuracy and precision of echocardiography-derived AA diameters compared with non-ECG gated HRCT measurements. Results: A total of 105 IPF patients and 102 age-, sex-, and CV risk factor-matched controls without IPF were evaluated retrospectively. Over a follow-up of 3.9 ± 1.9 yrs, 31 patients died and 47 were re-hospitalized. AA/height (HR 1.15, 95% CI 1.06-1.25, p < 0.001) was independently associated with the primary endpoint, whereas unindexed AA (HR 1.01, 95% CI 0.96-1.06, p = 0.83) and AA/BSA (HR 1.00, 95% CI 0.89-1.11, p = 0.39) were not. An AA/height > 20 mm/m showed 100% sensitivity and 63% specificity (AUC = 0.78) for predicting the primary endpoint. C-reactive protein (OR 1.87; 95% CI 1.21-2.89, p = 0.005) and left ventricular mass index (OR 1.13, 95% CI 1.04-1.24, p = 0.006) were independently associated with an AA/height > 20 mm/m in the whole study group. The Bland-Altman analysis revealed a bias of +2.51 mm (with the 95% limits of agreement ranging from -3.62 to 8.65 mm) for AA estimation, suggesting a general overestimation of the AA diameter by TTE in comparison to HRCT. Conclusions: AA dilatation is predictive of poor outcomes in IPF patients without advanced lung disease over a mid-term follow-up. The AA/height assessment may improve the prognostic risk stratification of IPF patients.

PMID:40004830 | DOI:10.3390/jcm14041300

J Clin Med. 2025 Feb 8;14(4):1093. doi: 10.3390/jcm14041093.

ABSTRACT

Interstitial lung diseases (ILDs) represent a heterogenous group of lung disorders marked by inflammation and/or fibrosis of the lung parenchyma, often leading to progressive shortness of breath and end-stage respiratory failure. In the U.S., ILDs affect approximately 650,000 individuals and cause approximately 25,000-30,000 deaths annually. Lung transplantation (LTx) offers definitive treatment for advanced ILD, with improved survival attributed to advancements in immunosuppression, organ preservation, surgical techniques, and postoperative care. However, disease recurrence in transplanted lungs remains a significant concern. Understanding the risk factors and mechanisms underlying recurrence is critical for refining recipient selection and improving outcomes. This review examines ILD recurrence post LTx and its implications for lung transplantation success.

PMID:40004625 | DOI:10.3390/jcm14041093

Diagnostics (Basel). 2025 Feb 16;15(4):474. doi: 10.3390/diagnostics15040474.

ABSTRACT

Hyperpolarized xenon-129 MRI (129XeMRI) has emerged as a powerful tool in the identification, evaluation, and assessment of disease endotyping and in response to interventions for a myriad of pulmonary diseases. Growing investigative efforts ranging from basic science to application in translational research have employed 129XeMRI in the evaluation of pulmonary conditions such as chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), asthma, and cystic fibrosis (CF). The novel feature of 129XeMRI is its ability to generate anatomic and physiologic readouts of the lung with resolution from the whole lung down to the lobar level. Additional advantages include being non-invasive and non-radioactive, and utilizing an inexpensive and ubiquitous noble gas as an inhalation contrast agent: xenon-129. In this review, we outline the clinical advances provided by 129XeMRI among common pulmonary diseases with high healthcare burdens in recent decades.

PMID:40002625 | DOI:10.3390/diagnostics15040474

RSC Med Chem. 2025 Feb 11. doi: 10.1039/d4md00475b. Online ahead of print.

ABSTRACT

The stimulator of interferon genes (STING) has been an attractive target in cancer immunotherapy. However, natural ligand cyclic dinucleotides (CDNs) and CDN derivatives have demonstrated limited efficacy in clinical trials. This limitation stems from the inherent structure of CDNs, which leads to enzymatic degradation, poor cell internalisation, rapid clearance from the tumour microenvironment, and dose-limiting toxicity. In this study, we developed an amphipathic STING agonist, termed albumin-binding CDNs (AlbiCDNs), to enhance the efficacy of c-di-GMP (CDG) via a lipid-conjugated strategy. The lipid provided a platform for albumin hitchhiking, which facilitated the cytoplasmic delivery of CDG without the use of any exogenous components. In addition, incorporating a stimuli-responsive lipid motif further enhanced the cellular release of CDG. Our results indicated that CDG-1C14, an AlbiCDN, efficiently stimulated the maturation and activation of antigen-presenting cells through STING activation. Furthermore, CDG-1C14 exhibited a significant inhibitory effect on the tumour therapeutic model. Therefore, AlbiCDN is a potent platform for cancer immunotherapy that can expedite clinical translation.

PMID:40008189 | PMC:PMC11848399 | DOI:10.1039/d4md00475b

Front Microbiol. 2025 Feb 11;16:1495971. doi: 10.3389/fmicb.2025.1495971. eCollection 2025.

ABSTRACT

INTRODUCTION: Bacteroides fragilis (Bf)'s T6SS locus has been characterized and shown to have functional activity in competition experiments. It has been demonstrated that symbiont nontoxigenic Bf strains have a more effective "weapon" effect on pathogenic Bf, which is realized through the activity of effector-immune (E-I) protein pairs. Intensive study of the T6SS structure has led to an understanding of certain issues related to its functional activity, but the exact regulatory mechanisms of E-I protein pair activity remain unclear. Proteomic annotation of T6SS components and detailed descriptions of all immune-effector pairs are currently available. In this research, we performed detailed proteogenomic analysis and subsequent proteomic annotation of the T6SS components of the toxigenic Bf BOB25.

MATERIAL AND METHODS: Fractionated cells, cultivated media and vesicles were prepared for proteome analysis by HPLC-MS/MS. Proteogenomic annotation and comparative genomic study of the T6SS loci of the toxigenic Bf BOB25 were carried out by comparison with the reference genomes of the following Bf strains: JIM10, NCTC 9343 and 638R.

RESULTS: According to the data obtained, T6SS components were represented in all types of the analysed samples. The following components of the T6SS were identified in culture media and cells: ClpV (TssH), TssK, TssC, TssB, Hcp (TssD), and TetR. The predicted effector protein AKA51715.1 (VU15_08315) was also detected in media. The greatest amount of T6SS proteins, including the Hcp protein, was detected in the vesicle samples, which was also observed by TEM. Potential effectors, including AKA51715.1 (VU15_08315), AKA51716.1 (VU15_08320), AKA51728.1 (VU15_08385) and the immune protein AKA51727.1 (VU15_08380), were detected in vesicles.

DISCUSSION: The presence of the immune and effector proteins in the Bf secretome indicates the high activity of the T6SS without bacterial competition. It is possible that the T6SS is also used by bacteria to regulate population size by altering the activity of different repertoires of E-I pairs.

PMID:40008042 | PMC:PMC11854122 | DOI:10.3389/fmicb.2025.1495971

Front Microbiol. 2025 Feb 11;16:1541797. doi: 10.3389/fmicb.2025.1541797. eCollection 2025.

ABSTRACT

The ArcAB two-component system includes a histidine kinase sensor (ArcB) and a regulator (ArcA) that respond to changes in cell oxygen availability. The ArcA transcription factor activates genes related to metabolism, membrane permeability, and virulence, and its presence is required for pathogenicity in Salmonella Typhimurium, which can be phosphorylated independently of its cognate sensor, ArcB. In this study, we aimed to characterize the transcriptional response to hypochlorous acid (HOCl) mediated by the presence of the ArcB sensor. HOCl is a powerful microbicide widely used for sanitization in industrial settings. We used wild-type S. Typhimurium and the mutant lacking the arcB gene exposed to NaOCl to describe the global transcriptional response. We also infected murine neutrophils to evaluate the expression levels of relevant genes related to the resistance and infection process while facing ROS-related stress. Our results indicate that the absence of the arcB gene significantly affects the ability of S. Typhimurium to grow under HOCl stress. Overall, 6.6% of Salmonella genes varied their expression in the mutant strains, while 8.6% changed in response to NaOCl. The transcriptional response associated with the presence of ArcB is associated with metabolism and virulence, suggesting a critical role in pathogenicity and fitness, especially under ROS-related stress. Our results show that ArcB influences the expression of genes associated with fatty acid degradation, protein secretion, cysteine and H2S biosynthesis, and translation, both in vitro and under conditions found within neutrophils. We found that protein carbonylation is significantly higher in the mutant strain than in the wild type, suggesting a critical function for ArcB in the response and repair processes. This study contributes to the understanding of the pathogenicity and adaptation mechanisms that Salmonella employs to establish a successful infection in its host.

PMID:40008041 | PMC:PMC11850377 | DOI:10.3389/fmicb.2025.1541797

Biophys J. 2025 Feb 25:S0006-3495(25)00106-7. doi: 10.1016/j.bpj.2025.02.015. Online ahead of print.

ABSTRACT

The molecular interactions between a fungal membrane model and SJGAP, a 32-amino-acid antimicrobial peptide (AMP) derived from skipjack tuna GAPDH, as well as four analogs, were investigated using molecular dynamics simulations and Fourier-transform infrared (FTIR) spectroscopy. In a previous study, Analog 7, modified by replacing three alanine residues with leucine residues, exhibited unique antifungal activity without any antibacterial effect. This contrasts with other analogs, which showed both antifungal and antibacterial effects. In the present study, Analog 7 displayed the strongest interactions with the membrane's hydrophobic core, inserting more deeply and causing significantly greater membrane deformation and thinning compared to the other analogs. Its presence caused significant membrane deformation, evident from the displacement of both the phosphate groups and terminal methyls of the lipids. Notably, Analog 7 was the only analog to induce a marked depletion of ergosterol around the peptide insertion site. Fourier-transform infrared (FTIR) spectroscopy experiments further confirmed the distinctive impact of Analog 7 on a fungal membrane model. The combined results from molecular dynamics simulations and spectroscopy emphasize the critical role of leucine substitutions in Analog 7, particularly at residues 18 and 19 within the central α helix, in promoting membrane thinning and inducing ergosterol depletion, suggesting increased membrane permeabilization, which could explain its previously reported antifungal specificity. This study provides the first insights into the molecular interactions between a GAPDH-derived AMP and a fungal membrane model, offering valuable information about its antifungal mechanism of action.

PMID:40007119 | DOI:10.1016/j.bpj.2025.02.015

Sensors (Basel). 2025 Feb 19;25(4):1264. doi: 10.3390/s25041264.

ABSTRACT

Perennial ryegrass is an important temperate grass used for forage and turf worldwide. It forms symbiotic relationships with endophytic fungi (endophytes), conferring pasture persistence and resistance to herbivory. Endophyte performance can be influenced by the host genotype, as well as environmental factors such as seed storage conditions. It is therefore critical to confirm seed quality and purity before a seed is sown. DNA-based methods are often used for quality control purposes. Recently, near-infrared spectroscopy (NIRS) coupled with hyperspectral imaging was used to discriminate perennial ryegrass cultivars and endophyte presence in individual seeds. Here, a NIRS-based analysis of bulk seeds was used to develop models for discriminating perennial ryegrass cultivars (Alto, Maxsyn, Trojan and Bronsyn), each hosting a suite of eight to eleven different endophyte strains. Sub-sampling, six per bag of seed, was employed to minimize misclassification error. Using a nested PLS-DA approach, cultivars were classified with an overall accuracy of 94.1-98.6% of sub-samples, whilst endophyte presence or absence was discriminated with overall accuracies between 77.8% and 96.3% of sub-samples. Hierarchical classification models were developed to discriminate bulked seed samples quickly and easily with minimal misclassifications of cultivars (<8.9% of sub-samples) or endophyte status within each cultivar (<11.3% of sub-samples). In all cases, greater than four of the six sub-samples were correctly classified, indicating that innate variation within a bag of seeds can be overcome using this strategy. These models could benefit turf- and pasture-based industries by providing a tool that is easy, cost effective, and can quickly discriminate seed bulks based on cultivar and endophyte content.

PMID:40006495 | DOI:10.3390/s25041264

Pharmaceuticals (Basel). 2025 Jan 24;18(2):152. doi: 10.3390/ph18020152.

ABSTRACT

In the original publication [...].

PMID:40006093 | DOI:10.3390/ph18020152

Pharmaceuticals (Basel). 2025 Feb 15;18(2):261. doi: 10.3390/ph18020261.

ABSTRACT

Long-lasting brain fatigue is a consequence of stroke or traumatic brain injury associated with emotional, psychological, and physical overload, distress in hypertension, atherosclerosis, viral infection, and aging-related chronic low-grade inflammatory disorders. The pathogenesis of brain fatigue is linked to disrupted neurotransmission, the glutamate-glutamine cycle imbalance, glucose metabolism, and ATP energy supply, which are associated with multiple molecular targets and signaling pathways in neuroendocrine-immune and blood circulation systems. Regeneration of damaged brain tissue is a long-lasting multistage process, including spontaneously regulating hypothalamus-pituitary (HPA) axis-controlled anabolic-catabolic homeostasis to recover harmonized sympathoadrenal system (SAS)-mediated function, brain energy supply, and deregulated gene expression in rehabilitation. The driving mechanism of spontaneous recovery and regeneration of brain tissue is a cross-talk of mediators of neuronal, microglia, immunocompetent, and endothelial cells collectively involved in neurogenesis and angiogenesis, which plant adaptogens can target. Adaptogens are small molecules of plant origin that increase the adaptability of cells and organisms to stress by interaction with the HPA axis and SAS of the stress system (neuroendocrine-immune and cardiovascular complex), targeting multiple mediators of adaptive GPCR signaling pathways. Two major groups of adaptogens comprise (i) phenolic phenethyl and phenylpropanoid derivatives and (ii) tetracyclic and pentacyclic glycosides, whose chemical structure can be distinguished as related correspondingly to (i) monoamine neurotransmitters of SAS (epinephrine, norepinephrine, and dopamine) and (ii) steroid hormones (cortisol, testosterone, and estradiol). In this narrative review, we discuss (i) the multitarget mechanism of integrated pharmacological activity of botanical adaptogens in stress overload, ischemic stroke, and long-lasting brain fatigue; (ii) the time-dependent dual response of physiological regulatory systems to adaptogens to support homeostasis in chronic stress and overload; and (iii) the dual dose-dependent reversal (hormetic) effect of botanical adaptogens. This narrative review shows that the adaptogenic concept cannot be reduced and rectified to the various effects of adaptogens on selected molecular targets or specific modes of action without estimating their interactions within the networks of mediators of the neuroendocrine-immune complex that, in turn, regulates other pharmacological systems (cardiovascular, gastrointestinal, reproductive systems) due to numerous intra- and extracellular communications and feedback regulations. These interactions result in polyvalent action and the pleiotropic pharmacological activity of adaptogens, which is essential for characterizing adaptogens as distinct types of botanicals. They trigger the defense adaptive stress response that leads to the extension of the limits of resilience to overload, inducing brain fatigue and mental disorders. For the first time, this review justifies the neurogenesis potential of adaptogens, particularly the botanical hybrid preparation (BHP) of Arctic Root and Ashwagandha, providing a rationale for potential use in individuals experiencing long-lasting brain fatigue. The review provided insight into future research on the network pharmacology of adaptogens in preventing and rehabilitating long-lasting brain fatigue following stroke, trauma, and viral infections.

PMID:40006074 | DOI:10.3390/ph18020261

Microorganisms. 2025 Jan 28;13(2):291. doi: 10.3390/microorganisms13020291.

ABSTRACT

The ilvBNC operon in Corynebacterium glutamicum encodes key enzymes for the biosynthesis of branched-chain amino acids (L-isoleucine, L-leucine, and L-valine). This operon has been studied for quite a long time, and it is assumed that three hairpin mRNA structures can be formed in its regulatory region; however, their functionality and role in the attenuation mechanism of the ilvBNC operon are not completely clear. In the present work, we performed a mutational analysis of mRNA secondary structures in the regulatory region of the C. glutamicum ilvBNC operon, which allowed us to propose a model of the regulation of its transcription involving three mRNA hairpins that essentially act as a transcription terminator, an antiterminator, and an antiantiterminator. In this work, we proved the existence of a transcription terminator in this operon and experimentally confirmed the effectiveness of its influence on the expression of the ilvBNC operon, AHAS enzyme activity, and valine production. We demonstrated the unique functional features of this attenuator, which, due to the overlapping of the terminator and antiterminator hairpins, is capable of rapid low-energy transitions between them without the complete disruption of the hairpin structures.

PMID:40005659 | DOI:10.3390/microorganisms13020291

Microorganisms. 2025 Jan 25;13(2):268. doi: 10.3390/microorganisms13020268.

ABSTRACT

Ammonia, essential for fertilizers and energy storage, is mainly produced through the energy-demanding Haber-Bosch process. Microbial production offers a sustainable alternative, but natural yeast cells have not yet demonstrated success. This study aimed to enhance ammonia production in Saccharomyces cerevisiae by optimizing amino acid utilization through its deamination metabolism. Adaptive laboratory evolution is a method for rapidly generating desirable phenotypes through metabolic and transcriptional reorganization. We applied it to the efficiently fermenting S. cerevisiae strain CEN.PK113-7D using an unbalanced carbon/nitrogen medium to impose selective pressure. We selected several evolved strains with a 3-5-fold increase in amino acid utilization and ammonia secretion. The multi-step bioreactor strategy of the evolved strain AAV6, supplemented with concentrated nitrogen sources, resulted in the production of 1.36 g/L of ammonia, a value in line with levels produced by other microbial systems. This proof-of-concept study suggests that yeast-based processes can be adapted straightforwardly to ammonia production from high-protein waste derived from several sources.

PMID:40005635 | DOI:10.3390/microorganisms13020268

Nutrients. 2025 Feb 7;17(4):604. doi: 10.3390/nu17040604.

ABSTRACT

Background: Individuals diagnosed with autism spectrum disorder (ASD) commonly experience sensory processing that differs from general-population norms, and the autistic lived experience of eating includes preferences for routine, and sensory processing difficulty related to scents, tastes, temperatures, and textures of food. Meanwhile, research indicates that nutrients involved in one-carbon metabolism (OCM) may be related to sensory processing. Methods: This study enrolled 33 school-aged children with autism to assess whether OCM nutrient intake is associated with sensory processing. Parents completed two parent-report assessments: the youth and adult food frequency questionnaire (YAFFQ), and a sensory processing tool, Sensory Profile 2 (SP2). Results: Participant data showed generally good nutritional profiles mirroring those of general-population U.S. children. A group-binarized linear regression model showed the following relationships (p < 0.05): vitamin B12 consumption had a negative association with the SP2 Oral and Sensor domain scores. Choline intake had a positive association with the SP2 Avoider domain score. Vitamin B1 showed a positive association with the SP2 Visual domain score. Conclusions: These results support the possible existence of a relationship between sensory symptoms and OCM nutrient consumption levels in school-aged children diagnosed with autism. Future research is needed to confirm and explore the potential for causality.

PMID:40004933 | DOI:10.3390/nu17040604

Genes (Basel). 2025 Feb 17;16(2):229. doi: 10.3390/genes16020229.

ABSTRACT

BACKGROUND/OBJECTIVES: Prostate cancer (PC) is the most common non-cutaneous cancer in men globally, and one which displays significant racial disparities. Men of African descent (AF) are more likely to develop PC and face higher mortality compared to men of European descent (EU). The biological mechanisms underlying these differences remain unclear. Long non-coding RNAs (lncRNAs), recognized as key regulators of gene expression and immune processes, have emerged as potential contributors to these disparities. This study aimed to investigate the regulatory role of lncRNAs in localized PC in AF men relative to those of EU and assess their involvement in immune response and inflammation.

METHODS: A systems biology approach was employed to analyze differentially expressed (DE) lncRNAs and their roles in prostate cancer (PC). Immune-related pathways were investigated through over-representation analysis of lncRNA-mRNA networks. The study also examined the effects of vitamin D supplementation on lncRNA expression in African descent (AF) PC patients, highlighting their potential regulatory roles in immune response and inflammation.

RESULTS: Key lncRNAs specific to AF men were identified, with several being implicated for immune response and inflammatory processes. Notably, 10 out of the top 11 ranked lncRNAs demonstrated strong interactions with immune-related genes. Pathway analysis revealed their regulatory influence on antigen processing and presentation, chemokine signaling, and ribosome pathways, suggesting their critical roles in immune regulation.

CONCLUSIONS: These findings highlight the pivotal role of lncRNAs in PC racial disparities, particularly through immune modulation. The identified lncRNAs may serve as potential biomarkers or therapeutic targets to address racial disparities in PC outcomes.

PMID:40004558 | DOI:10.3390/genes16020229

Int J Mol Sci. 2025 Feb 11;26(4):1520. doi: 10.3390/ijms26041520.

ABSTRACT

Tick bites and tick-related diseases are on the rise. Diagnostic tests that identify well-characterised tick-borne pathogens (TBPs) possess limited capacity to address the causation of symptoms associated with poorly characterised tick-related illnesses, such as debilitating symptom complexes attributed to ticks (DSCATT) in Australia. Identification of local signals in tick-bitten skin that can be detected systemically in blood would have both clinical (diagnostic or prognostic) and research (mechanistic insight) utility, as a blood sample is more readily obtainable than tissue biopsies. We hypothesised that blood samples may reveal signals which reflect relevant local (tissue) events and that the time course of these signals may align with local pathophysiology. As a first step towards testing this hypothesis, we compared molecular signatures in skin biopsies taken from the tick-bite location of human participants, as published in our previous study, together with peripheral blood signatures obtained concurrently. This approach captures differentially expressed molecules across multiple omics datasets derived from peripheral blood (including cellular and cell-free transcriptomics, proteomics, metabolomics, and DNA methylation), and skin biopsies (spatial transcriptomics). Our original data revealed that extracellular matrix organisation and platelet degranulation pathways were upregulated in the skin within 72 h of a tick bite. The same signals appeared in blood, where they then remained elevated for three months, displaying longitudinally consistent alterations of biological functions. Despite the limited sample size, these data represent proof-of-concept that molecular events in the skin following a tick bite can be detectable systemically. This underscores the potential value of blood samples, akin to a liquid biopsy, to capture biomarkers reflecting local tissue processes.

PMID:40003986 | DOI:10.3390/ijms26041520

Insects. 2025 Feb 19;16(2):230. doi: 10.3390/insects16020230.

ABSTRACT

Grape phylloxera, Daktulosphaira vitifoliae (Fitch), is an economically significant pest of grapevines. Identification of phylloxera genotypes is an important aspect of management as genotypes differ in virulence and susceptibility to control using resistant rootstocks. Microsatellite markers developed on polyacrylamide gel systems have been the most widely used molecular method for phylloxera genotype identification, but this approach has been superseded by fluorescent capillary-based genotyping. The current study presents new laboratory methods for amplifying a standard set of eight phylloxera microsatellite markers using PCR-incorporated fluorescently labelled primers, genotyped on an ABI capillary platform. Comparison of allele size data scored on (i) polyacrylamide, (ii) capillary, and (iii) high-throughput sequencing (HTS) platforms revealed that the capillary genotyping most closely matched the HTS allele sizes, while alleles of loci originally scored on a polyacrylamide platform differ in size by up to three base pairs, mostly due to the presence of previously uncharacterised DNA sequence indels. Seven common clonal lineages of phylloxera known from Australia are proposed as reference samples for use in calibrating genotyping systems between platforms and laboratories to ensure universal scoring of allele sizes, providing a critical link for accurately matching previous phylloxera genotype studies with current research.

PMID:40003859 | DOI:10.3390/insects16020230

Entropy (Basel). 2025 Jan 22;27(2):106. doi: 10.3390/e27020106.

ABSTRACT

Spontaneous pattern formation is a universal phenomenon that occurs in purely physical systems, biology, and human societies. Salt fingering due to differential diffusion of heat and salt in seawater is a typical example, although the general principle that governs pattern formation remains unknown. We show through simple experiments injecting a salt solution into a sucrose solution of equal density that a salt finger exhibits characteristic pattern transitions depending on the injection flow rate. When the rate increases, a linear finger starts meandering, branching, and multiple branching, whereas when the rate is decreased, it produces a beading pattern. These morphological instabilities and associated pattern formation are caused by a local accumulation of kinetic energy that minimizes the flow resistance and maximizes the energy dissipation in the final steady state. We suggest that this energy accumulation mechanism governs a wide variety of pattern formation phenomena in non-equilibrium systems, including morphogenesis of abiotic protocells.

PMID:40003103 | DOI:10.3390/e27020106