Sci Rep. 2025 Mar 26;15(1):10359. doi: 10.1038/s41598-025-95021-x.

ABSTRACT

To use the FDA Adverse Event Reporting System (FAERS) database to identify drugs associated with orthostatic hypotension. Adverse event reports of orthostatic hypotension from Q1 2004 to Q3 2024 were obtained from the FAERS and JADER databases. We employed algorithms such as the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multi-item gamma Poisson shrinker (MGPS) for signal detection. JADER database was used to validate the findings from FAERS analysis. We identified 15,737 adverse events associated with orthostatic hypotension, involving 15,480 patients for analysis. The patient demographic included 6,745 males (43.5%) and 7,248 females (46.8%), with the largest group comprising adults over 65 years (7,654 cases, 49.4%). The three drugs with the highest ROR risk signals were terazosin [ROR (95% CI): 153.96 (124.57-190.28)], rasagiline [ROR (95% CI): 37.46 (29.99-46.78)], and doxazosin [ROR (95% CI): 37.06 (31.32-43.86)]. Apomorphine, abalopatine and levodopa were associated with the shortest onset time of orthostatic hypotension. Most of the signal detection results from the FAERS database were verified in the JADER database. Drugs associated with orthostatic hypertension still focused on cardiovascular and nervous system drugs. This study employed the FAERS database to identify 33 drugs that may be potentially linked to orthostatic hypotension. Medical workers should remain vigilant regarding the risk of these drugs causing orthostatic hypotension.

PMID:40133436 | DOI:10.1038/s41598-025-95021-x

Metabolites. 2025 Feb 27;15(3):159. doi: 10.3390/metabo15030159.

ABSTRACT

Background: Aging is characterized by shared cellular and molecular processes, and aging-related diseases might co-exist in a cluster of comorbidities, particularly in vulnerable individuals whose phenotype meets the criteria for frailty. Whilst the multidimensional definition of frailty is still controversial, there is an increasing understanding of the common pathways linking metabolic syndrome, cognitive decline, and sarcopenia, frequent conditions in frail elderly patients. Methods: We performed a systematic search in the electronic databases Cochrane Library and PubMed and included preclinical studies, cohort and observational studies, and trials. Discussion: Metabolic syndrome markers, such as insulin resistance and the triglyceride/HDL C ratio, correlate with early cognitive impairment. Insulin resistance is a cause of synaptic dysfunction and neurodegeneration. Conversely, fasting and fasting-mimicking agents promote neuronal resilience by enhancing mitochondrial efficiency, autophagy, and neurogenesis. Proteins acting as cellular metabolic sensors, such as SIRT1, play a pivotal role in aging, neuroprotection, and metabolic health. In AD, β-amyloid accumulation and hyperphosphorylated tau in neurofibrillary tangles can cause metabolic reprogramming in brain cells, shifting from oxidative phosphorylation to aerobic glycolysis, similar to the Warburg effect in cancer. The interrelation of metabolic syndrome, sarcopenia, and cognitive decline suggests that targeting these shared metabolic pathways could mitigate all the conditions. Pharmacological interventions, including GLP-1 receptor agonists, metformin, and SIRT 1 inducers, demonstrated neuroprotective effects in animals and some preliminary clinical models. Conclusions: These findings encourage further research on the prevention and treatment of neurodegenerative diseases as well as the drug-repurposing potential of molecules currently approved for diabetes, dyslipidemia, and metabolic syndrome.

PMID:40137124 | DOI:10.3390/metabo15030159

Metabolites. 2025 Feb 25;15(3):156. doi: 10.3390/metabo15030156.

ABSTRACT

BACKGROUND/OBJECTIVES: Neutrophil cells' lysis forms the extracellular traps (NETs) to counter the foreign body during insults to the body. Peptidyl arginine deiminase (PAD) participates in this process and is then released into the extracellular fluid with the lysed cell components. In some diseases, patients with abnormal function of PADs, especially PAD 4, tend to form autoantibodies against the abnormal citrullinated proteins that are the result of PAD activity on arginine side chains. Those antibodies, which are highly distinct in RA, are distinctly anti-citrullinated protein antibodies (ACPA). This study used an in-silico drug repurposing approach of FDA-approved medications to identify potential alternative medications that can inhibit this process and address solutions to the current limitations of existing therapies.

METHODS: We utilized Maestro Schrödinger as a computational tool for preparing and docking simulations on the PAD 4 enzyme crystal structure that is retrieved from RCSB Protein Data Bank (PDB ID: 4X8G) while the docked FDA-approved medications are obtained from the Zinc 15 database. The protein was bound to GSK 199-an investigational compound-as a positive control for the docked molecules. Preparation of the protein was performed by Schrödinger Protein Preparation Wizard tool. Binding pocket determination was performed by Glide software (Schrödinger Release 2021-3:Schrödinger, LLC., New York, NY, USA, 2021). and validation of molecular docking was carried out through the redocking of GSK 199 and superimposition. After that, standard and induced fit docking were performed.

RESULTS/CONCLUSIONS: Among the four obtained hits Pemetrexed, Leucovorin, Chlordiazepoxide, and Ioversol, which showed the highest XP scores providing favorable binding interactions. The induced-fit docking (IFD) results displayed the strong binding affinities of Ioversol, Pemetrexed, Leucovorin, Chlordiazepoxide in the order IFD values -11.617, -10.599, -10.521, -9.988, respectively. This research investigates Pemetrexed, Leucovorin, Chlordiazepoxide, and Ioversol as potential repurposing agents in the treatment of rheumatoid arthritis (RA) as they are identified as PAD4 inhibitors.

PMID:40137121 | DOI:10.3390/metabo15030156

Curr Issues Mol Biol. 2025 Feb 26;47(3):153. doi: 10.3390/cimb47030153.

ABSTRACT

Metastatic endometrial cancer continues to be a common cause of death as of 2024, even after maximal use of all currently available standard treatments. To address this problem of metastatic cancer generally in 2025, the drug repurposing movement within oncology identifies medicines in common general medical use that have clinical or preclinical experimental data indicating that they interfere with or inhibit a specific growth driving element identified in a given cancer. The drug repurposing movement within oncology also uses data from large scale in vitro screens of thousands of drugs, looking for simple empirical growth inhibition in a given cancer type. This paper outlines the data showing that five drugs from general medical practice meet these evidence criteria for inhibition of endometrial cancer growth, the EC5 regimen. The EC5 regimen uses the osteoporosis treatment drug, alendronate; the analgesic drug, celecoxib; the antifungal drug, itraconazole; the sleep aid, ramelteon; and the cholesterol lowering drug, simvastatin. Side effects seen with these drugs are usually minimal and easily tolerated by patients.

PMID:40136407 | DOI:10.3390/cimb47030153

mBio. 2025 Mar 26:e0020525. doi: 10.1128/mbio.00205-25. Online ahead of print.

ABSTRACT

Coccidioidomycosis or valley fever is a treatment-limited fungal infection endemic to the alkaline deserts of North and South America for which two classes of antifungals are typically used: the polyenes and the triazoles. In light of the limited usefulness of the echinocandins and a growing trend of azole resistance, it is essential that we identify novel antifungals. In this study, we have developed and optimized a screening methodology for identifying potential antifungals effective against Coccidioides spherule initials using a metabolic assay, used it to screen four diverse drug libraries with limited drug overlap, and established safety and efficacy data for a majority of the compounds, including the Broad Repurposing Hub, Prestwick Chemicals 1520, Selleck L8200 Anti-parasitic, and MedChemExpress CNS Penetrants libraries. Hits were defined as compounds with strong metabolic inhibition (≥70%), which were significantly different compared to the median plate readout (B-scores ≤ -3). We identified 30 promising hits and found 12 compounds exhibiting half-maximal inhibitory concentrations below 6 µM. Among these, oxethazaine, niclosamide ethanolamine, 10058-F4, niclosamide (NIC), and pentamidine isethionate showed synergy with amphotericin B, suggesting their potential use in combination therapy. Further assessment of lead compounds' effects on spherules was conducted by image flow cytometry. Additionally, we explored the potential to use an attenuated, Biosafety Level 2 containment mutant, C. posadasii ∆cts2/∆ard1/∆cts3 (∆T), as a surrogate model for drug screening. Overall, our findings provide a foundation for future research focused on screening and developing novel coccidioidomycosis treatments.IMPORTANCEThe antifungal treatment arsenal is especially limited against Coccidioides. Due to toxicity concerns, amphotericin B is generally reserved for triazole-recalcitrant infections. Recent laboratory susceptibility tests show an increase in fluconazole resistance, highlighting a need for new treatments. We have developed a large-scale metabolic screening assay under Biosafety Level 3 containment to identify existing drugs with novel activity against Coccidioides spherules. This drug-repurposing approach represents a convenient and cost-effective strategy to increase the available antifungals effective against these infections.

PMID:40135873 | DOI:10.1128/mbio.00205-25

J Biomol Struct Dyn. 2025 Mar 26:1-12. doi: 10.1080/07391102.2025.2483963. Online ahead of print.

ABSTRACT

Poly (ADP-ribose) polymerase 1 (PARP1) is a nuclear protein that plays a pivotal role in DNA repair and has emerged as a promising target for cancer therapy. Repurposing existing FDA-approved drugs for PARP1 inhibition offers an accelerated route to drug discovery. Here, we present an integrated approach to drug repurposing for PARP1 inhibition while utilizing an integrated approach involving structure-based virtual screening and molecular dynamics (MD) simulations. First, a curated library of 3648 FDA-approved drugs from DrugBank was screened to identify potential candidates capable of binding to the PARP1. Our study reveals a subset of drug molecules with favorable binding profiles and stable interactions within the PARP1 active site. The standout candidate, Nilotinib, was selected based on its drug profile and subjected to a detailed analysis, including interaction studies and 500 ns all-atom MD simulations. By integrating multiple computational approaches, we provide a rational framework for the selection of Nilotinib, demonstrating its PARP1 binding features and potential for therapeutic development after further experimentation. This study highlights the power of computational methods in accelerating drug repurposing efforts, offering an efficient strategy for identifying novel therapeutic options for PARP1-associated diseases.

PMID:40135853 | DOI:10.1080/07391102.2025.2483963

Clin Pract. 2025 Mar 7;15(3):54. doi: 10.3390/clinpract15030054.

ABSTRACT

Background/Objectives: During the last decade, there has been an increased interest in phenolic compound-rich natural products as natural therapies for regulating the molecular pathways behind central obesity and associated metabolic disorders. The present scoping review presents the outcomes of clinical and preclinical studies examining the anti-obesity effects of high phenolic extra virgin olive oil (HP-EVOO) and its possible underlying molecular mechanisms. Methods: Studies published between 2014 and 2024 were searched via MEDLINE, Scopus, Cochrane, the Web of Science, Semantic Scholar, Google Scholar, Science.gov, and Clinicaltrials.gov databases. A combination of keywords and Boolean logic was used to search throughout the last decade in all databases, including "hyperglycemia" or "hypertension" or "metabolic syndrome" or "dyslipidemia" or "hyperlipidemia" or "hypoglycemia" or "obesity" or "macrovascular diabetic complications" or "microvascular diabetic complications" or "cardiovascular disease" or "overweight" or "insulin sensitivity" or "insulin resistance" and "extra virgin olive oil" or "high phenolic olive oil" and "human" or "animal model". Results: The 10-year literature survey identified 21 studies in both animal models and humans, indicating that HP-EVOO improves inflammation, glycemic control, oxidative stress and endothelial function, potentially protecting against metabolic syndrome, hypertension and type 2 diabetes, even compared to EVOO. Moreover, HP-EVOO's antiplatelet effect and improvement in HDL functionality reduce cardiovascular risk. Conclusions: The evidence presented in this study demonstrates that HP-EVOO represents an effective preventive and therapeutic dietary approach to cardiometabolic diseases.

PMID:40136590 | DOI:10.3390/clinpract15030054

J Pers Med. 2025 Mar 13;15(3):110. doi: 10.3390/jpm15030110.

ABSTRACT

Background/Objectives: Pharmacogenomics is an emerging field in precision medicine that aims to improve patient outcomes by tailoring drug selection and dosage to an individual's genetic makeup. However, patients in rural communities often cannot take advantage of specialized services such as pharmacogenomics due to various barriers that limit access to healthcare. This article aims to identify the barriers to implementing pharmacogenomic initiatives in rural communities and assess strategies for integrating pharmacogenomics into rural healthcare systems. Methods: This article describes the qualitative research that was conducted using semi-structured interviews with various stakeholders in addition to explaining how strategic frameworks were used to synthesize secondary research. Results: The findings of this article indicated mixed awareness of pharmacogenomics as an option amongst stakeholders, highlighting the need for targeted outreach and education intervention. Solutions such as mail-in testing and telemedicine were determined to be feasible solutions to address various geographical and logistical barriers that exist for rural patients. This article determines that successful strategies will leverage existing infrastructure and prioritize patient care, workflow integration, and adoption. Conclusions: Making pharmacogenomics a viable option for rural patients will take a multi-faceted approach that combines outreach, education, and innovative delivery models to overcome the multiple barriers facing rural communities.

PMID:40137426 | DOI:10.3390/jpm15030110

J Pers Med. 2025 Mar 5;15(3):103. doi: 10.3390/jpm15030103.

ABSTRACT

Background: In the United States, approximately 1 in 5 children experience comorbidities with mental illness, including depression and anxiety, which lead to poor general health outcomes. Adolescents with substance use disorders exhibit high rates of co-occurring mental illness, with over 60% meeting diagnostic criteria for another psychiatric condition in community-based treatment programs. Comorbidities are influenced by both genetic (DNA antecedents) and environmental (epigenetic) factors. Given the significant impact of psychiatric comorbidities on individuals' lives, this study aims to uncover common mechanisms through a Genome-Wide Association Study (GWAS) meta-meta-analysis. Methods: GWAS datasets were obtained for each comorbid phenotype, followed by a GWAS meta-meta-analysis using a significance threshold of p < 5E-8 to validate the rationale behind combining all GWAS phenotypes. The combined and refined dataset was subjected to bioinformatic analyses, including Protein-Protein Interactions and Systems Biology. Pharmacogenomics (PGx) annotations for all potential genes with at least one PGx were tested, and the genes identified were combined with the Genetic Addiction Risk Severity (GARS) test, which included 10 genes and eleven Single Nucleotide Polymorphisms (SNPs). The STRING-MODEL was employed to discover novel networks and Protein-Drug interactions. Results: Autism Spectrum Disorder (ASD) was identified as the top manifestation derived from the known comorbid interaction of anxiety, depression, and attention deficit hyperactivity disorder (ADHD). The STRING-MODEL and Protein-Drug interaction analysis revealed a novel network associated with these psychiatric comorbidities. The findings suggest that these interactions are linked to the need to induce "dopamine homeostasis" as a therapeutic outcome. Conclusions: This study provides a reliable genetic and epigenetic map that could assist healthcare professionals in the therapeutic care of patients presenting with multiple psychiatric manifestations, including anxiety, depression, and ADHD. The results highlight the importance of targeting dopamine homeostasis in managing ASD linked to these comorbidities. These insights may guide future pharmacogenomic interventions to improve clinical outcomes in affected individuals.

PMID:40137419 | DOI:10.3390/jpm15030103

J Pers Med. 2025 Mar 4;15(3):101. doi: 10.3390/jpm15030101.

ABSTRACT

Background/Objectives: While there is mounting scientific evidence supporting the effectiveness of PGx (pharmacogenomics)-guided medical treatment, its implementation into clinical care is still lagging. Stakeholder buy-in, in particular from prescribers, will be key in the implementation efforts. Previous implementation studies have primarily focused on prescriber attitudes or have used hypothetical scenario methodology in a variety of healthcare settings. Real-world studies provide better insight into prescriber experience and needs. In this prospective observational qualitative research study, we report the perspectives of prescribers working in military medical care after a one-year PGx implementation trial. Methods: At the end of the PGx implementation period, thirteen prescribers participated in a semi-structured interview. The interview was designed based on the Technology Acceptance Model and queried their perceptions of effectiveness and ease of use of the PGx innovation. Results: Three main themes emerged from the qualitative data: (1) the knowledge required for PGx testing, (2) the integration of the testing into the existing workflow and (3) the perceived clinical utility of the PGx results. Prescribers had educational and training opportunities prior to the study but still encountered difficulty with the interpretation of the test results. They generally managed well the workflow changes occasioned by the testing. They reported that the clinical value came primarily from an increased confidence in prescribing safe medications and improving the therapeutic alliance with their patients. There was uncertainty about which patient population would most benefit from the testing. Conclusions: Our results lend support to the general ongoing challenges identified in PGx implementation studies conducted in other clinical settings and using other methodologies. They also revealed specific factors that the prescribers found of value and areas that needed improvement to support future implementation efforts.

PMID:40137417 | DOI:10.3390/jpm15030101

J Pers Med. 2025 Feb 28;15(3):93. doi: 10.3390/jpm15030093.

ABSTRACT

Background: Certain CYP2D6 genotypes are linked to a lower efficacy of tamoxifen therapy. This study aimed to observe CYP2D6 polymorphisms and examine the impact of CYP2D6 genotyping among tamoxifen-treated breast cancer patients in Indonesia. Methods: 150 breast cancer participants were recruited. Buccal swab samples were collected; gDNA was extracted and genotyped using the qPCR method. Blood samples were collected, and measurement of tamoxifen metabolite levels was performed using UPLC-MS/MS. Results: 43.3% (n = 65) of participants were IMs. *10 was the most common haplotype (n = 89, 29.7%), followed by *36 (n = 73, 29.7%), making *10/*36 the most common diplotype (n = 34, 22.7%) in this study. The difference in endoxifen levels between the NM and IM-PM groups at baseline was statistically significant (p ≤ 0.001). A dose increase in tamoxifen to 40 mg daily successfully increased endoxifen levels in IMs to a similar level with NMs at baseline (p > 0.05) without exposing IMs to serious side effects. No statistically significant differences were observed between the 20mg group and the 40 mg group on the adjusted OS (p > 0.05) and the adjusted PFS (p > 0.05). Conclusions: Our study observed a considerably high proportion of CYP2D6 IMs. The dose adjustment of tamoxifen was proven to significantly and safely improve the level of endoxifen and survival.

PMID:40137409 | DOI:10.3390/jpm15030093

J Fungi (Basel). 2025 Mar 9;11(3):210. doi: 10.3390/jof11030210.

ABSTRACT

Cystic fibrosis is a severe, inherited, life-limiting disorder, and over half of those living with CF are children. Persistent airway infection and inflammation, resulting in progressive lung function decline, is the hallmark of this disorder. Aspergillus colonization and infection is a well-known complication in people with CF and can evolve in a range of Aspergillus disease phenotypes, including Aspergillus bronchitis, fungal sensitization, and allergic bronchopulmonary aspergillosis (ABPA). Management strategies for children with CF are primarily aimed at preventing lung damage and lung function decline caused by bacterial infections. The role of Aspergillus infections is less understood, especially during childhood, and therefore evidence-based diagnostic and treatment guidelines are lacking. This narrative review summarizes our current understanding of the impact of Aspergillus on the airways of children and young people with CF.

PMID:40137248 | DOI:10.3390/jof11030210

Cells. 2025 Mar 19;14(6):459. doi: 10.3390/cells14060459.

ABSTRACT

Polycystic kidney disease (PKD) is the most common hereditary disorder that disrupts renal function and frequently progresses to end-stage renal disease. Recent advances have elucidated the critical role of primary cilia and ciliary ion channels, including transient receptor potential (TRP) channels, cystic fibrosis transmembrane conductance regulator (CFTR), and polycystin channels, in the pathogenesis of PKD. While some channels primarily function as chloride conductance channels (e.g., CFTR), others primarily regulate calcium (Ca+2) homeostasis. These ion channels are essential for cellular signaling and maintaining the normal kidney architecture. Dysregulation of these pathways due to genetic mutations in PKD1 and PKD2 leads to disrupted Ca+2 and cAMP signaling, aberrant fluid secretion, and uncontrolled cellular proliferation, resulting in tubular cystogenesis. Understanding the molecular mechanisms underlying these dysfunctions has opened the door for innovative therapeutic strategies, including TRPV4 activators, CFTR inhibitors, and calcimimetics, to mitigate cyst growth and preserve renal function. This review summarizes the current knowledge on the roles of ciliary ion channels in PKD pathophysiology, highlights therapeutic interventions targeting these channels, and identifies future research directions for improving patient outcomes.

PMID:40136708 | DOI:10.3390/cells14060459

Cells. 2025 Mar 9;14(6):400. doi: 10.3390/cells14060400.

ABSTRACT

Pulmonary homeostasis can be agitated either by external environmental insults or endogenous factors produced during respiratory/pulmonary diseases. The lungs counter these insults by initiating mechanisms of inflammation as a localized, non-specific first-line defense response. Cytokines are small signaling glycoprotein molecules that control the immune response. They are formed by numerous categories of cell types and induce the movement, growth, differentiation, and death of cells. During respiratory diseases, multiple proinflammatory cytokines play a crucial role in orchestrating chronic inflammation and structural changes in the respiratory tract by recruiting inflammatory cells and maintaining the release of growth factors to maintain inflammation. The issue aggravates when the inflammatory response is exaggerated and/or cytokine production becomes dysregulated. In such instances, unresolving and chronic inflammatory reactions and cytokine production accelerate airway remodeling and maladaptive outcomes. Pro-inflammatory cytokines generate these deleterious consequences through interactions with receptors, which in turn initiate a signal in the cell, triggering a response. The cytokine profile and inflammatory cascade seen in different pulmonary diseases vary and have become fundamental targets for advancement in new therapeutic strategies for lung diseases. There are considerable therapeutic approaches that target cytokine-mediated inflammation in pulmonary diseases; however, blocking specific cytokines may not contribute to clinical benefit. Alternatively, broad-spectrum anti-inflammatory approaches are more likely to be clinically effective. Herein, this comprehensive review of the literature identifies various cytokines (e.g., interleukins, chemokines, and growth factors) involved in pulmonary inflammation and the pathogenesis of respiratory diseases (e.g., asthma, chronic obstructive pulmonary, lung cancer, pneumonia, and pulmonary fibrosis) and investigates targeted therapeutic treatment approaches.

PMID:40136649 | DOI:10.3390/cells14060400

Rev Paul Pediatr. 2025 Mar 24;43:e2024155. doi: 10.1590/1984-0462/2025/43/2024155. eCollection 2025.

ABSTRACT

OBJECTIVE: Determine the immediate effect of forced expiration technique (FET) on the respiratory mechanics of children and adolescents with cystic fibrosis (CF). As a secondary objective, the effect of cough induced by FET was evaluated by comparing respiratory mechanics and lung function between those who coughed and those who did not during the FET.

METHODS: A before-after clinical trial was conducted with children and adolescents with CF aged six to 15 years. Respiratory mechanics parameters were assessed using the impulse oscillometry system (IOS) in three stages: basal IOS, post-huff IOS, and final post-diaphragmatic breathing exercises (DBE) IOS. For the intervention, FET was requested with five low-volume followed by three high-volume huffs, and finally ten DBE repetitions. Coughing occurred randomly and was not previously requested. To investigate whether FET-induced coughing alters oscillometric parameters, the participants were divided into two groups: those who presented with cough (CG) during the protocol and those who did not (NCG).

RESULTS: Forty-three children and adolescents with CF participated in the study (51.2% female), with an average age of 10.44±2.64 years, where forced expiratory value - FEV1=78.51±23.28%, and body mass index - BMI=17.18±2.24 kg/m2. The huffing sequence increased all oscillometric parameters, while DBE repetitions led to an increase in these parameters, without a complete return to baseline values. In terms of coughing, there was no significant difference between the NCG and CG in any of the parameters studied.

CONCLUSIONS: It was observed that, during the FET, diaphragmatic breathing exercises can attenuate the effort exerted by the forced expiratory maneuver on the airways.

PMID:40136119 | DOI:10.1590/1984-0462/2025/43/2024155

J Bacteriol. 2025 Mar 26:e0002925. doi: 10.1128/jb.00029-25. Online ahead of print.

ABSTRACT

Pseudomonas aeruginosa is an opportunistic pathogen that uses several mechanisms to survive in the iron-limiting host environment. The innate immune protein calprotectin (CP) sequesters ferrous iron [Fe(II)], among other divalent transition metal ions, to limit its availability to pathogens. CP levels are increased in individuals with cystic fibrosis (CF), a hereditary disease that leads to chronic pulmonary infection by P. aeruginosa. We previously showed that aerobic CP treatment of P. aeruginosa induces a multi-metal starvation response that alters expression of several virulence properties. However, the CF lung is a hypoxic environment due to the growth of P. aeruginosa in dense biofilms. Here, we report that anaerobic CP treatment of P. aeruginosa induces many processes associated with an aerobic iron starvation response, including decreased phenazine production and increased expression of the PrrF small regulatory RNAs (sRNAs). However, the iron starvation response elicited by CP in anaerobic conditions shows characteristics that are distinct from responses observed in aerobic growth, including a lack of siderophore production and increased induction of genes for the FeoAB Fe(II) and Phu heme uptake systems. Also distinct from aerobic conditions, CP treatment induces expression of genes for predicted manganese transporters MntH1 and MntH2 during anaerobic growth while eliciting a less robust zinc starvation response compared to aerobic conditions. Induction of mntH2 is dependent on the PrrF sRNAs, suggesting a novel example of metal regulatory cross-talk. Thus, anaerobic CP treatment results in a multi-metal starvation response with key distinctions from aerobic conditions, revealing differences in P. aeruginosa metal homeostasis during anaerobic growth.IMPORTANCEIron is critical for most microbial pathogens, and the innate immune system sequesters this metal to limit microbial growth. Pathogens must overcome iron sequestration to survive during infection. For many pathogens, iron homeostasis has primarily been studied in aerobic conditions. Nevertheless, some host environments are hypoxic, including chronic lung infection sites in individuals with cystic fibrosis (CF). Here, we use the innate immune protein calprotectin, which sequesters divalent metal ions including Fe(II), to study the anaerobic iron starvation response of a common CF lung pathogen, Pseudomonas aeruginosa. We report several distinctions of this response during anaerobiosis, highlighting the importance of carefully considering the host environment when investigating the role of nutritional immunity in host-pathogen interactions.

PMID:40135923 | DOI:10.1128/jb.00029-25

J Bacteriol. 2025 Mar 26:e0011623. doi: 10.1128/jb.00116-23. Online ahead of print.

ABSTRACT

Staphylococcus aureus asymptomatically colonizes the nasal cavity and pharynx of up to 60% of the human population and, as an opportunistic pathogen, can breach its normal habitat, resulting in life-threatening infections. S. aureus infections are of additional concern for populations with impaired immune function such as those with cystic fibrosis (CF) or chronic granulomatous disease. Multi-drug resistance is increasingly common in S. aureus infections, creating an urgent need for new antimicrobials or compounds that improve efficacy of currently available antibiotics. S. aureus biofilms, such as those found in the lungs of people with CF and in soft tissue infections, are notoriously recalcitrant to antimicrobial treatment due to the characteristic metabolic differences associated with a sessile mode of growth. In this work, we show that another CF pathogen, Burkholderia cenocepacia, produces one or more secreted compounds that can prevent S. aureus biofilm formation and inhibit existing S. aureus biofilms. The B. cenocepacia-mediated antagonistic activity is restricted to S. aureus species and perhaps some other staphylococci; however, this inhibition does not necessarily extend to other Gram-positive species. This inhibitory activity is due to death of S. aureus through a contact-independent mechanism, potentially mediated through the siderophore pyochelin and perhaps additional compounds. This works paves the way to better understanding of interactions between these two bacterial pathogens.IMPORTANCEStaphylococcus aureus is a major nosocomial pathogen responsible for infecting thousands of people each year. Some strains are becoming increasingly resistant to antimicrobials, and consequently new treatments must be sought. This paper describes the characterization of one or more compounds capable of inhibiting S. aureus biofilm formation and may potentially lead to development of a new therapeutic.

PMID:40135855 | DOI:10.1128/jb.00116-23

J Pers Med. 2025 Mar 20;15(3):121. doi: 10.3390/jpm15030121.

ABSTRACT

(1) Background: Helminth infections are a widespread global health concern, with Ascaris and taeniasis representing two of the most prevalent infestations. Traditional diagnostic methods, such as egg-based microscopy, are fraught with challenges, including subjectivity and low throughput, often leading to misdiagnosis. This study evaluates the efficacy of advanced deep learning models in accurately classifying Ascaris lumbricoides and Taenia saginata eggs from microscopic images, proposing a technologically enhanced approach for diagnostics in clinical settings. (2) Methods: Three state-of-the-art deep learning models, ConvNeXt Tiny, EfficientNet V2 S, and MobileNet V3 S, are considered. A diverse dataset comprising images of Ascaris, Taenia, and uninfected eggs was utilized for training and validating these models by performing multiclass experiments. (3) Results: All models demonstrated high classificatory accuracy, with ConvNeXt Tiny achieving an F1-score of 98.6%, followed by EfficientNet V2 S at 97.5% and MobileNet V3 S at 98.2% in the experiments. These results prove the potential of deep learning in streamlining and improving the diagnostic process for helminthic infections. The application of deep learning models such as ConvNeXt Tiny, EfficientNet V2 S, and MobileNet V3 S shows promise for efficient and accurate helminth egg classification, potentially significantly enhancing the diagnostic workflow. (4) Conclusion: The study demonstrates the feasibility of leveraging advanced computational techniques in parasitology and points towards a future where rapid, objective, and reliable diagnostics are standard.

PMID:40137437 | DOI:10.3390/jpm15030121

J Funct Morphol Kinesiol. 2025 Feb 22;10(1):73. doi: 10.3390/jfmk10010073.

ABSTRACT

BACKGROUND/OBJECTIVES: Falls among the older adult population represent a significant public health concern, often leading to diminished quality of life and serious injuries that escalate healthcare costs, and they may even prove fatal. Accurate fall risk prediction is therefore crucial for implementing timely preventive measures. However, to date, there is no definitive metric to identify individuals with high risk of experiencing a fall. To address this, the present study proposes a novel approach that transforms biomechanical time-series data, derived from gait analysis, into visual representations to facilitate the application of deep learning (DL) methods for fall risk assessment.

METHODS: By leveraging convolutional neural networks (CNNs) and Siamese neural networks (SNNs), the proposed framework effectively addresses the challenges of limited datasets and delivers robust predictive capabilities.

RESULTS: Through the extraction of distinctive gait-related features and the generation of class-discriminative activation maps using Grad-CAM, the random forest (RF) machine learning (ML) model not only achieves commendable accuracy (83.29%) but also enhances explainability.

CONCLUSIONS: Ultimately, this study underscores the potential of advanced computational tools and machine learning algorithms to improve fall risk prediction, reduce healthcare burdens, and promote greater independence and well-being among the older adults.

PMID:40137325 | DOI:10.3390/jfmk10010073

J Imaging. 2025 Mar 20;11(3):91. doi: 10.3390/jimaging11030091.

ABSTRACT

Human activity recognition (HAR) has emerged as a transformative field with widespread applications, leveraging diverse sensor modalities to accurately identify and classify human activities. This paper provides a comprehensive review of HAR techniques, focusing on the integration of sensor-based, vision-based, and hybrid methodologies. It explores the strengths and limitations of commonly used modalities, such as RGB images/videos, depth sensors, motion capture systems, wearable devices, and emerging technologies like radar and Wi-Fi channel state information. The review also discusses traditional machine learning approaches, including supervised and unsupervised learning, alongside cutting-edge advancements in deep learning, such as convolutional and recurrent neural networks, attention mechanisms, and reinforcement learning frameworks. Despite significant progress, HAR still faces critical challenges, including handling environmental variability, ensuring model interpretability, and achieving high recognition accuracy in complex, real-world scenarios. Future research directions emphasise the need for improved multimodal sensor fusion, adaptive and personalised models, and the integration of edge computing for real-time analysis. Additionally, addressing ethical considerations, such as privacy and algorithmic fairness, remains a priority as HAR systems become more pervasive. This study highlights the evolving landscape of HAR and outlines strategies for future advancements that can enhance the reliability and applicability of HAR technologies in diverse domains.

PMID:40137203 | DOI:10.3390/jimaging11030091