Brain Behav. 2025 Jan;15(1):e70200. doi: 10.1002/brb3.70200.

ABSTRACT

INTRODUCTION: The cognitive side-effects of medication are common, but often overlooked in practice, and not routinely considered in interventional trials or post-market surveillance. The cognitive footprint of a medication seeks to quantify the impact of its cognitive effects based on magnitude, duration, and interaction with other factors, evaluated across the exposed population.

METHODS: Bayesian multivariable regression analysis of retrospective population-based cross-sectional cohorts.

RESULTS: We replicate positive and negative cognitive effects of commonly used medications in UK Biobank, and extend observed associations to two additional cohorts, the EPIC Norfolk, and the Caerphilly Prospective Cohort. We quantify the resultant cumulative impact at the population level given known patterns of prescribing and compare it with exemplar common diseases.

CONCLUSION: The cognitive side-effects of commonly used drugs may have significant impact at the population level. Consideration should be given to a routine structured assessment of cognition in interventional trials and post-market surveillance.

PMID:39829148 | DOI:10.1002/brb3.70200

Cell Rep. 2025 Jan 18;44(2):115220. doi: 10.1016/j.celrep.2024.115220. Online ahead of print.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease characterized by excess accumulation of the extracellular matrix (ECM). The role of macrophage-fibroblast crosstalk in lung fibrogenesis is incompletely understood. Here we found that fibroblast growth factor-inducible molecule 14 (Fn14), the receptor for tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is highly induced in myofibroblasts in the lungs of IPF patients and the bleomycin-induced lung fibrosis model. TWEAK-Fn14 signaling inhibits fibroblast activation and ECM synthesis and induces chemokine expression to recruit monocytes/macrophages into the lung. Fn14 deficiency increases ECM production and impairs macrophage infiltration and differentiation, leading to exacerbated lung fibrosis and impaired alveolar regeneration in a bleomycin model. Interestingly, Fn14 deficiency diminishes an injury-induced SiglecF- CD11b- MHCIIlo intermediate macrophage (IntermM) subpopulation, which promotes alveolar type II (AT2) cell proliferation in organoid cultures. These results collectively demonstrate a protective role of TWEAK-Fn14 signaling in lung fibrosis, highlighting the complexities and multilayered regulation of macrophage-fibroblast crosstalk.

PMID:39827460 | DOI:10.1016/j.celrep.2024.115220

J Biol Chem. 2025 Jan 17:108206. doi: 10.1016/j.jbc.2025.108206. Online ahead of print.

ABSTRACT

It has been well established that adenosine plays a key role in the control of inflammation through G protein coupled receptors and recently shown that it can regulate thermogenesis. Here we investigated the specific requirements of the adenosine A2A receptor (A2AR) in mature adipocytes for thermogenic functionality and metabolic homeostasis. We generated fat tissue specific adenosine A2A receptor knock-out mice to assess the influence of signaling through this receptor on brown and beige fat functionality, obesity, insulin sensitivity, inflammation and liver function. Fat specific A2AR knock-out and wild type littermate mice were compared for potential differences in cold tolerance and energy metabolism. In addition, we measured glucose metabolism, AT inflammation and liver phenotypes in mice of the two genotypes after exposure to a diet rich in fat. Our results provide novel evidence indicating that loss of the adenosine A2A receptor specifically in adipocytes is associated with cold intolerance and decreased oxygen consumption. Furthermore, mice with fat specific ablation of the A2AR exposed to a diet rich in fat showed increased propensity to obesity, decreased insulin sensitivity, elevated adipose tissue inflammation and hepato-steatosis and -steatitis. Overall, our data provide novel evidence that A2AR in mature adipocytes safeguards metabolic homeostasis, suggesting the possibility of targeting this receptor selectively in fat for the treatment of metabolic disease.

PMID:39828097 | DOI:10.1016/j.jbc.2025.108206

N Biotechnol. 2025 Jan 17:S1871-6784(25)00006-8. doi: 10.1016/j.nbt.2025.01.005. Online ahead of print.

ABSTRACT

In order to improve predictability of outcome and reduce costly rounds of trial-and-error, machine learning models have been of increasing importance in the field of synthetic biology. Besides applications in predicting genome annotation, process parameters and transcription initiation frequency, such models have also been of help for pathway optimization. The latter is a common strategy in metabolic engineering and improves the production of a desirable compound by optimizing enzyme expression levels of the production pathway. However, engineering steps might not lead to sufficient improvement, and bottlenecks may remain hidden among the hundreds of metabolic reactions occurring in a living cell, especially if the production pathway is highly interconnected with other parts of the cell's metabolism. Here, we use the synthesis of chitooligosaccharides (COS) to show that the production from such complex pathways can be improved by using machine learning models and feature importance analysis to find new compounds with an impact on COS production. We screened Escherichia coli libraries of engineered transcription regulators with an expected broad range of metabolic diversity and trained several machine learning models to predict COS production titers. Subsequent feature analysis led to the finding of iron, whose addition we could show improved COS production in vivo up to 2-fold. Additionally, the analysis revealed important clues for future engineering steps.

PMID:39827984 | DOI:10.1016/j.nbt.2025.01.005

Comput Biol Med. 2025 Jan 18;186:109624. doi: 10.1016/j.compbiomed.2024.109624. Online ahead of print.

ABSTRACT

Studying and analysing the various phases and key proteins of cell cycles is essential for the understanding of cell development and differentiation. To this end, mechanistic models play an important role towards a system level understanding of the interactions between cell cycle components. Many quantitative models of cell cycles have been previously constructed using either stochastic or deterministic approaches. However, cell cycle models are inherently hybrid requiring the full and accurate interplay of the continuous system dynamics and their corresponding discrete events. Moreover, not all required experimental data are usually available when designing in-silico experiments for these scenarios. In this paper, we employ hybrid Petri nets to implement a hybrid model of the Caulobacter crescentus cell cycle. The model handles all required logics of cell cycles in a very elegant way. We then extend this model to support fuzzy kinetics for those parts where sufficient experimental data are not available and thus precise kinetic parameters cannot be estimated. With some of the kinetic parameters being set as fuzzy numbers, the model produces uncertain bands of outputs reflecting different possibilities of an output comprising most likely the correct one.

PMID:39827734 | DOI:10.1016/j.compbiomed.2024.109624

Sci Rep. 2025 Jan 19;15(1):2452. doi: 10.1038/s41598-025-86422-z.

ABSTRACT

Misoprostol was originally used to treat gastric ulcers, and has been widely used in abortion, cervical maturation, induced labour and postpartum hemorrhage. But there are still many undetected adverse events (AEs). The purpose of this study was to provide a comprehensive overview of the safety of misoprostol. Adverse events related to misoprostol were collected from the FDA Adverse Event Reporting System (FAERS) database from the first quarter of 2004 to the second quarter of 2024. This study used proportional disequilibrium methods such as reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and empirical Bayes geometric mean (EBGM) to detect AEs. After analyzing 17,427,762 adverse event reports, a total of 2032 adverse events reports related to misoprostol were identified, involving 23 system organ classes and 30 preferred terms. The most common AEs were foetal exposure during delivery(n = 201), uterine tachysystole(n = 95), uterine rupture (n = 95), and heart rate decreased (n = 93). Although most AEs complied with the drug instruction, new AEs signals such as congenital aqueductal stenosis and congenital brain damage were also identified. Clinicians should make appropriate evaluation when using misoprostol, closely monitor the indicators of patients, and have appropriate countermeasures for possible adverse events.

PMID:39828758 | DOI:10.1038/s41598-025-86422-z

Zhonghua Yi Xue Za Zhi. 2025 Jan 21;105(3):233-239. doi: 10.3760/cma.j.cn112137-20240725-01713.

ABSTRACT

Objective: To evaluate the efficacy of domestic and imported sugammadex for reversal of rocuronium-induced deep neuromuscular block (NMB) in adult patients. Methods: The clinical data of adult patients who scheduled for elective surgery with general anesthesia that required muscle relaxants in Peking University First Hospital from June 2023 to June 2024 were prospectively included. The patients were devided into domestic group and imported group according to random number table method. Anesthetized patients received rocuronium for intubation and muscle relaxation, and anesthesia was maintained with propofol, sevoflurane, and remifentanil. The effect of neuromuscular block was monitored. During deep muscle relaxation (with a single stimulation muscle twitch count of 1-2 after tetanic stimulation), domestic and imported sugammadex 4 mg/kg was given, respectively. The primary outcome was the recovery time from sugammadex injection to return of the train-of-four ratio (TOFr) to 0.9, with a non-inferiority margin of 1 minute (the range of non-inferiority boundary value is ±1 minute). The secondary outcome included the ratios of TOFr to 0.9 at different times and adverse effects. Results: A total of 70 patients were included, including 35 patients in the domestic group (13 males and 22 females), aged (46.9±12.7) years, and 35 patients in the imported group (13 males and 22 females), aged (45.7±11.5) years. There was no statistically significant difference in demographic characteristics, surgical time, anesthesia time, total rocuronium dose, and extubation time between two groups. All patients recovered to a TOFr of 0.9 within 5 minutes. Reversal time was 1.8 (1.3, 2.6) minutes in the domestic sugammadex group and 2.0 (1.7, 2.9) minutes in the imported sugammadex group respectively. The difference in reversal times between two groups was -0.40 minutes (95%CI:-0.75 to -0.02, P=0.039), which was within the range of non-inferiority threshold. Within 5 minutes of administration of antagonists, the incidence of bradycardia was 14% (5/35 and 5/35) in both domestic and imported groups. The incidence of skin allergy in patients transported to the post-anesthesia recovery room (PACU) was 3% (3/35) and 0 in both groups, respectively, with no statistical significance (all P>0.05). There were no serious drug-related adverse events in both groups. Conclusion: The effect of domestic sugammadex is not inferior to imported sugammadex in reversal of deep rocuronium-induced neuromuscular block in adult patients, and the incidence of postoperative adverse events is not increased.

PMID:39828581 | DOI:10.3760/cma.j.cn112137-20240725-01713

Dig Liver Dis. 2025 Jan 18:S1590-8658(25)00038-6. doi: 10.1016/j.dld.2025.01.037. Online ahead of print.

ABSTRACT

BACKGROUND: Immune-related sclerosing cholangitis (irSC) induced by immune checkpoint inhibitors (ICIs) is relatively rare, and its clinical and pathological features are not well known.

AIMS: We aimed to compare the clinical course and pathological findings of irSC with those of non-irSC liver injury.

METHODS: Clinical data were retrospectively collected from 2416 patients with advanced malignancies treated with ICIs between September 2014 and October 2023. The data of patients with severe ICI-induced liver injury who underwent liver biopsy were analyzed and compared between patients with irSC and non-irSC.

RESULTS: Ninety-three (3.8 %) patients had severe ICI-induced liver injury, and 38 underwent liver biopsy. Of these, five were diagnosed with irSC. The irSC group had a significantly longer time to onset of ICI-induced liver injury and a lower rate of improvement of liver injury than did the non-irSC group (irSC, 3/5; non-irSC, 32/33). Liver biopsies revealed more moderate-to-severe pathological cholangitis in the irSC group than in the non-irSC group (irSC, n = 5/5; non-irSC, n = 16/33). Other pathological findings were similar between the two groups.

CONCLUSION: Appropriate management of irSC requires an understanding of its characteristics of late onset and steroid resistance, and liver biopsy, in addition to imaging, may be useful for diagnosing irSC.

PMID:39828442 | DOI:10.1016/j.dld.2025.01.037

Hum Vaccin Immunother. 2025 Dec;21(1):2449714. doi: 10.1080/21645515.2025.2449714. Epub 2025 Jan 19.

ABSTRACT

To analyze the coverage rate of adult herpes zoster (HZ) vaccine and the incidence of Adverse event following immunization (AEFI) in Jiangsu province, China. The vaccination information of HZ vaccine in people aged 50 years and above in Jiangsu province in 2023 and the AEFI information of HZ vaccine from 2020 to 2023 were collected through the Jiangsu Province vaccination management information system and China AEFI information management system, and the vaccination rate and AEFI incidence of HZ vaccine were analyzed. The overall vaccination rate among individuals aged 50 years and above was merely 0.19%. About 20% of vaccinated individuals (12,821 people) received only the first dose, failing to complete the recommended two-dose regimen. A total of 43 and 217 cases of AEFIs following vaccination were reported after administration of the HZ vaccine during the periods of 2020-2021 and 2022-2023, respectively, resulting in reporting rates (RRs) of 240.7 and 201.2 per 100,000 doses, correspondingly. The majority of AEFIs following vaccination with HZ vaccines were common reactions, while rare reactions and coincidental events accounted for only 1.5% and 0.4% of cases, respectively. Over 55% of AEFIs occurred within 30 minutes post-vaccination , with fever, allergic eruptions, and drowsiness being the most reported systemic symptoms, and redness and induration being the main symptoms at the injection site. Despite the proven safety profile of the HZ vaccine, its coverage remains significantly low among individuals aged 50 years and above in Jiangsu Province, China as of 2023. The majority of AEFIs were mild and commonly observed. To enhance the comprehensiveness of post-marketing safety data, it is imperative to conduct further active surveillance studies.

PMID:39827897 | DOI:10.1080/21645515.2025.2449714

Eur J Radiol. 2025 Feb;183:111926. doi: 10.1016/j.ejrad.2025.111926. Epub 2025 Jan 13.

ABSTRACT

Pathologies of the vulva encompass a wide range of mesenchymal and epithelial benign and malignant lesions. Suspicion is raised by non-specific symptoms or clinical findings detected during routine gynecological examinations, and histopathology is essential for the diagnosis. The role of imaging has often been limited, but it can be essential in guiding treatment and, in some cases, in helping differential diagnosis. In particular, magnetic resonance imaging (MRI) can play a central role in identifying the extent of disease and planning surgical treatment. To this aim, rigorous image acquisition, correct disease evaluation in the context of vulvar anatomy and understanding of the possible differential diagnosis are essential. The aim of this article is to review the role of MRI in the evaluation of rare vulvar pathologies, focusing on different sites of origin, imaging characteristics, and local extent.

PMID:39826155 | DOI:10.1016/j.ejrad.2025.111926

J Clin Densitom. 2025 Jan-Mar;28(1):101559. doi: 10.1016/j.jocd.2024.101559. Epub 2024 Dec 28.

ABSTRACT

The 24th Annual Santa Fe Bone Symposium (SFBS) was held in Santa Fe, New Mexico, USA, on August 2-3, 2024. This was a "hybrid" meeting, with in-person and real-time remote participants representing a broad range of geographical locations and medical disciplines. The focus was on new developments in the care of patients with osteoporosis, other metabolic bone diseases, and inherited skeletal disorders. The most current medical evidence was presented and discussed with consideration of implications for patient management. Topics included an update on clinical uses of osteoanabolic agents, management of patients discontinuing denosumab, bone health optimization for orthopedic surgery, estrogen and testosterone in the management of osteoporosis, osteoporosis treatment in the very old, overview of rare bone diseases, treat-to-target for osteoporosis, and a progress report on global activities of Bone Health ECHO. There were two highly interactive faculty panel discussions - one with case presentations by attendees and another with open microphone for all topics of interest. Endocrinology fellows, selected from attendees of the Santa Fe Fellows Workshop on Metabolic Bone Diseases, held the two days preceding the SFBS, participated with presentations of oral abstracts. Ancillary events addressed modern approaches to menopause and bone health, case studies of management of patients at very high fracture risk, and management of patients with rare bone diseases, such as hypophosphatasia, fibrodysplasia ossificans progressiva, X-linked hypophosphatemia, and hypoparathyroidism. These proceedings of the SFBS present the clinical highlights of the plenary sessions and the discussions that followed.

PMID:39826229 | DOI:10.1016/j.jocd.2024.101559

Commun Biol. 2025 Jan 18;8(1):85. doi: 10.1038/s42003-025-07519-9.

ABSTRACT

Phosphodiesterase-5 (PDE5) inhibitors have shown promise as anti-cancer agents in malignancies. However, their specific effects on gastric cancer (GC) and the underlying mechanisms remain elusive. Our aim was to investigate this by combining evidence from population-based studies with data obtained from in vivo and in vitro experiments. By combing a couple of nationwide Swedish registers, GC patients who received PDE5 inhibitors were compared to matched controls while adjusting for confounding factors. The anti-tumor effect and mechanism of the PDE5 inhibitor sildenafil were evaluated via using tumor cells, patient-derived tumor organoids and xenograft animal models in GC. A total of 161 Swedish GC patients from a nationwide population-based cohort who received post-diagnostic PDE5 inhibitors demonstrated lower cancer-specific mortality compared to the controls (HR = 0.66, 95% CI = 0.47-0.92, P = 0.016). Functionally, the PDE5 inhibitor sildenafil exhibited the suppressive ability to prevent oncogenic growth in GC. Mechanistically, sildenafil restrained GC growth by directly activating PKG through PDE5 inhibition for regulating c-MYC expression via its phosphorylation and ubiquitination degradation, thereby suppressing c-MYC stability for IL-6 transcription within the downstream IL-6/JAK/STAT3 signalling pathway. The PDE5 inhibitor sildenafil may serve as a promising adjuvant for GC therapy if further randomized clinical trials confirm its efficacy.

PMID:39827331 | DOI:10.1038/s42003-025-07519-9

Cancer Lett. 2025 Jan 16:217437. doi: 10.1016/j.canlet.2025.217437. Online ahead of print.

NO ABSTRACT

PMID:39826666 | DOI:10.1016/j.canlet.2025.217437

Comput Methods Programs Biomed. 2025 Jan 13;261:108604. doi: 10.1016/j.cmpb.2025.108604. Online ahead of print.

ABSTRACT

BACKGROUND: Alzheimer's disease (AD), the most prevalent form of dementia, remains enigmatic in its origins despite the widely accepted "amyloid hypothesis," which implicates amyloid-beta peptide aggregates in its pathogenesis and progression. Despite advancements in technology and healthcare, the incidence of AD continues to rise. The traditional drug development process remains time-consuming, often taking years to bring an AD treatment to market. Drug repurposing has emerged as a promising strategy for developing cost-effective and efficient therapeutic options by identifying new uses for existing approved drugs, thus accelerating drug development.

OBJECTIVES: This study aimed to examine two key drug repurposing methodologies in general diseases and specifically in AD, which are artificial intelligent (AI) approach and molecular docking approach. In addition, the hybrid approach that integrates AI with molecular docking techniques will be explored too.

METHODOLOGY: This study systematically compiled a comprehensive collection of relevant academic articles, scientific papers, and research studies which were published up until November 2024 (as of the writing of this review paper). The final selection of papers was filtered to include studies related to Alzheimer's disease and general diseases, and then categorized into three groups: AI articles, molecular docking articles, and hybrid articles.

RESULTS: As a result, 331 papers were identified that employed AI for drug repurposing in general diseases, and 58 papers focused specifically in AD. For molecular docking in drug repurposing, 588 papers addressed general diseases, while 46 papers were dedicated to AD. The hybrid approach combining AI and molecular docking in drug repurposing has 52 papers for general diseases and 9 for AD. A comparative review was done across the methods, results, strengths, and limitations in those studies. Challenges of drug repurposing in AD are explored and future prospects are proposed.

DISCUSSION AND CONCLUSION: Drug repurposing emerges as a compelling and effective strategy within AD research. Both AI and molecular docking methods exhibit significant potential in this domain. AI algorithms yield more precise predictions, thus facilitating the exploration of new therapeutic avenues for existing drugs. Similarly, molecular docking techniques revolutionize drug-target interaction modelling, employing refined algorithms to screen extensive drug databases against specific target proteins. This review offers valuable insights for guiding the utilization of AI, molecular docking, or their hybrid in AD drug repurposing endeavors. The hope is to speed up the timeline of drug discovery which could improve the therapeutic approach to AD.

PMID:39826482 | DOI:10.1016/j.cmpb.2025.108604

Sci Rep. 2025 Jan 18;15(1):2390. doi: 10.1038/s41598-025-86211-8.

ABSTRACT

Burkholderia cenocepacia H111 is an obligate aerobic bacterium which has been isolated from a cystic fibrosis (CF) patient. In CF lungs the environment is considered micro-oxic or even oxygen-depleted due to bacterial activities and limited oxygen diffusion in the mucus layer. To adapt to low oxygen concentrations, bacteria possess multiple terminal oxidases. In this study, we identified six terminal oxidases of B. cenocepacia H111 and constructed reporter strains to monitor their expression in different environments. While the heme-copper oxidase aa3 (cta) was constitutively expressed, the bd-1 oxidase (cyd) was induced under oxygen-limited growth conditions. The cyanide-insensitive bd-type terminal oxidase (cio-1) was mainly expressed in cells grown on the surface of solid medium or in liquid cultures in presence of cyanide, which is known to be produced in the CF lung by the often co-residing CF pathogen Pseudomonas aeruginosa. Indeed, a cio-1 insertional mutant was not able to grow in the presence of cyanide confirming the important role of Cio-1 in cyanide resistance. The caa3 oxidase (caa), was only expressed under nutrient limitation when cells were grown on the surface of solid medium. We also investigated the involvement of two regulatory systems, Anr and RoxS/RoxR, in the expression of cio-1 and cyd. Our data suggest, that, given that Cio-1 is only present in prokaryotes and plays an important role in the defense against cyanide-producing P. aeruginosa, it may be a valuable drug target for treatment of polymicrobial infections in CF patients.

PMID:39827173 | DOI:10.1038/s41598-025-86211-8

Respir Res. 2025 Jan 18;26(1):19. doi: 10.1186/s12931-024-03089-2.

ABSTRACT

This retrospective population-based study investigated the impact of elexacaftor/tezacaftor/ivacaftor (ETI) therapy on inhaled medication adherence in people with cystic fibrosis (pwCF). Prescription refill rate (PRR) for several inhaled medications were compared before and after ETI introduction in three major Italian CF centers. We found a significant decrease in PRR for most inhaled antibiotics and dornase-alpha after ETI implementation.This suggests that patients may be reducing their adherence to inhaled medications, potentially due to improved respiratory symptoms and quality of life. The study highlights the challenges of maintaining adherence to chronic inhaled medications in pwCF, even after the introduction of breakthrough therapies like ETI. Monitoring adherence remains crucial for optimizing patient outcomes, and the PRR emerges as a valuable tool for tracking adherence in real-world settings.

PMID:39827103 | DOI:10.1186/s12931-024-03089-2

J Thorac Cardiovasc Surg. 2025 Feb;169(2):484-504. doi: 10.1016/j.jtcvs.2024.08.052.

ABSTRACT

BACKGROUND: Donor lung procurement and preservation is critical for lung transplantation success. Unfortunately, the large variability in techniques impacts organ utilization rates and transplantation outcomes. Compounding this variation, recent developments in cold static preservation and new technological advances with machine perfusion have increased the complexity of the procedure. The objective of the American Association for Thoracic Surgery (AATS) Clinical Practice Standards Committee (CPSC) expert panel was to make evidence-based recommendations for best practices in donor lung procurement and preservation based on review of the existing literature.

METHODS: The AATS CPSC assembled an expert panel of 16 lung transplantation surgeons from 14 centers who developed a consensus document of recommendations. The panel was divided into 7 subgroups covering (1) intraoperative donor assessment, (2) surgical techniques, (3) ex situ static lung preservation methods, (4) hypothermic preservation, (5) normothermic ex vivo lung perfusion (EVLP), (6) donation after circulatory death (DCD) and normothermic regional perfusion, and (7) donor management centers, organ assessment centers, and third-party procurement teams. Following a focused literature review, each subgroup formulated recommendation statements for each subtopic, which were reviewed and further refined using a Delphi process until a 75% consensus was achieved on each final statement by the voting group.

RESULTS: The expert panel achieved consensus on 34 recommendations for current best practices in donor lung procurement and preservation both in brain-dead as well as DCD donation. The use of new methods of cold preservation, the role of EVLP, and DCD with and without concomitant heart donation are described in detail.

CONCLUSIONS: Consistent and best practices in donor lung procurement and preservation are critical to improve both lung transplantation numbers as well as recipient outcomes. The recommendations described here provide guidance for professionals involved in the care of patients with end-stage lung disease considered for transplantation.

PMID:39826938 | DOI:10.1016/j.jtcvs.2024.08.052

Eur J Med Chem. 2025 Feb 15;284:117229. doi: 10.1016/j.ejmech.2024.117229. Epub 2024 Dec 30.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease for which few drugs are available in clinical practice. Here, we identified novel capsaicin analogs by combining in-house chemical library screening and further structural optimization. (E)-1-(3,4-dihydroxyphenyl)-7-phenylhept-1-en-3-one (Compound 14) was found to be the most potent in inhibiting TGF-β-induced collagen accumulation, proliferation and migration in fibroblast cells. Furthermore, compound 14 (IC50 = 0.51 ± 0.06 μM) showed over 100-fold increasing antifibrotic activity compared to capsaicin (IC50 = 53.71 ± 4.78 μM). Notably, compound 14 could target TRPV1, thereby affecting the expression of the fibrosis markers Collagen Ⅰ and α-SMA by inhibiting the TGF-β/Smads and MAPK pathways to exert antifibrotic activity in vitro. Compound 14 significantly inhibited collagen deposition in lung tissues, ameliorated alveolar structures, and increased survival rates in mice with bleomycin-induced pulmonary fibrosis. In addition, compound 14 possessed lower cytotoxicity (compared to nitedanib) and no toxicity in mice. Overall, compound 14 promise as a potential drug candidate for the treatment of IPF.

PMID:39826937 | DOI:10.1016/j.ejmech.2024.117229

Nat Commun. 2025 Jan 18;16(1):825. doi: 10.1038/s41467-025-56077-5.

ABSTRACT

As next-generation sequencing technologies produce deeper genome coverages at lower costs, there is a critical need for reliable computational host DNA removal in metagenomic data. We find that insufficient host filtration using prior human genome references can introduce false sex biases and inadvertently permit flow-through of host-specific DNA during bioinformatic analyses, which could be exploited for individual identification. To address these issues, we introduce and benchmark three host filtration methods of varying throughput, with concomitant applications across low biomass samples such as skin and high microbial biomass datasets including fecal samples. We find that these methods are important for obtaining accurate results in low biomass samples (e.g., tissue, skin). Overall, we demonstrate that rigorous host filtration is a key component of privacy-minded analyses of patient microbiomes and provide computationally efficient pipelines for accomplishing this task on large-scale datasets.

PMID:39827261 | DOI:10.1038/s41467-025-56077-5

Sci Rep. 2025 Jan 18;15(1):2368. doi: 10.1038/s41598-024-83942-y.

ABSTRACT

Antarctic environments are dominated by microorganisms, which are vulnerable to viral infection. Although several studies have investigated the phylogenetic repertoire of bacteria and viruses in these poly-extreme environments with freezing temperatures, high ultra violet irradiation levels, low moisture availability and hyper-oligotrophy, the evolutionary mechanisms governing microbial immunity remain poorly understood. Using genome-resolved metagenomics, we test the hypothesis that Antarctic poly-extreme high-latitude microbiomes harbour diverse adaptive immune systems. Our analysis reveals the prevalence of prophages in bacterial genomes (Bacteroidota and Verrucomicrobiota), suggesting the significance of lysogenic infection strategies in Antarctic soils. Furthermore, we demonstrate the presence of diverse CRISPR-Cas arrays, including Class 1 arrays (Types I-B, I-C, and I-E), alongside systems exhibiting novel gene architecture among their effector cas genes. Notably, a Class 2 system featuring type V variants lacks CRISPR arrays, encodes Cas1 and Cas2 adaptation module genes. Phylogenetic analysis of Cas12 effector proteins hints at divergent evolutionary histories compared to classified type V effectors and indicates that TnpB is likely the ancestor of Cas12 nucleases. Our findings suggest substantial novelty in Antarctic cas sequences, likely driven by strong selective pressures. These results underscore the role of viral infection as a key evolutionary driver shaping polar microbiomes.

PMID:39827180 | DOI:10.1038/s41598-024-83942-y