Literature Watch
The large milkweed bugs' Na,K-ATPase β-subunits colocalize with septate junction proteins in a tissue-specific manner
Cell Tissue Res. 2025 Mar 26. doi: 10.1007/s00441-025-03965-3. Online ahead of print.
ABSTRACT
The Na,K-ATPase is a vital transmembrane enzyme, which is important for maintaining cell membrane potentials and the general functionality of animal cells. The enzyme's minimal functional unit consists of one α and one β-subunit, whereas the number of existing paralogs varies in different insect species. The functional roles of different β-subunits, which can account for their diversity within a single species, are so far only partially explained. The emphasis of this study was to specifically elucidate the involvement in septate junctions of the four β-subunits of the new model system Oncopeltus fasciatus. Septate junctions function as a paracellular barrier controlling the flow of solutes across epithelia. So far, studies in Drosophila revealed that nervana2, the β2 homolog of Drosophila, is involved in septate junction formation. In O. fasciatus, we demonstrate that most of the Na,K-ATPase subunits colocalize with septate junction proteins. This agrees with our previous findings implying a role of β2 in the control of tracheal tube size in O. fasciatus, which according to the findings in Drosophila appears to be dependent on a stable formation of septate junctions. Finally, our data suggest a connection between the septate junction protein coracle and the enigmatic, N-terminally strongly truncated βx, which has no obvious homologs in other insects. Our study proposes that the four β-subunits form functional units with septate junction proteins, either allowing tissue-adjusted formation of cell-cell contacts or other yet unknown functions.
PMID:40137937 | DOI:10.1007/s00441-025-03965-3
The Effect of <em>Helicobacter pylori</em> Gene Combinations of <em>cagA</em>, <em>cagE</em>, <em>virB11</em>, <em>vacA</em>, and <em>babA</em> on the Outcome of Gastric Disease in a Southern Moroccan Population
Pathogens. 2025 Mar 14;14(3):279. doi: 10.3390/pathogens14030279.
ABSTRACT
Helicobacter pylori (H. pylori) possess an arsenal of virulence genes that makes them the main etiological factor in gastric diseases. In this study, 120 southern Moroccan patients who were dyspeptic were profiled to investigate the potential association between disease severity and the combination of multiple virulence genes. Gastric biopsies were taken from patients, followed by histopathological evaluation and genotyping of H. pylori using PCR. H. pylori was detected in 58.3% of cases, and genotypes were distributed as follows: oipA (94.3%), cagA (62.9%), virB11 (60%), babA (55.7%), dupA (54.3%), cagE (51.4%), iceA1 (31.4%), iceA2 (45.7%), vacA s2m2 (47.1%), vacA s1m1 (30%), and vacA s1m2 (7.1%). Statistically significant associations with males were observed for the cagA, cagE, and virB11 genes and multiple strain infections. Multivariate analysis revealed an association between cagE and heightened neutrophil activity, with an odds ratio (OR) of 4.99 (p = 0.03). The gene combination [cagA (+), cagE (+), virB11 (+), vacA s1m1, and babA (+)] emerged as a predictive factor for gastric cancer (OR = 11.10, p = 0.046), while the combination [cagA (-), cagE (-), virB11 (-), vacA s2m2, babA (+)] was associated with gastric atrophy (OR = 10.25, p = 0.016). Age (≤40 years) (OR = 5.87, p = 0.013) and moderate to severe bacterial density (OR = 15.38, p = 0.017) were identified as predictive factors for follicular gastritis. These findings underscore the significance of multigene profiling as a prognostic marker and emphasize the importance of age and sex in preventing adverse outcomes in severe gastric diseases.
PMID:40137764 | DOI:10.3390/pathogens14030279
High-Throughput Sequencing Enables Rapid Analyses of Nematode Mitochondrial Genomes from an Environmental Sample
Pathogens. 2025 Feb 27;14(3):234. doi: 10.3390/pathogens14030234.
ABSTRACT
Mitochondrial genomes serve as essential tools in evolutionary biology, phylogenetics, and population genetics due to their maternal inheritance, lack of recombination, and conserved structure. Traditional morphological methods for identifying nematodes are often insufficient for distinguishing cryptic species complexes. This study highlights recent advancements in nematode mitochondrial genome research, particularly the impact of long-read sequencing technologies such as Oxford Nanopore. These technologies have facilitated the assembly of mitochondrial genomes from mixed soil samples, overcoming challenges associated with designing specific primers for long PCR amplification across different groups of parasitic nematodes. In this study, we successfully recovered and assembled eleven nematode mitochondrial genomes using long-read sequencing, including those of two plant-parasitic nematode species. Notably, we detected Heterodera cruciferae in Victoria, expanding its known geographic range within Australia. Additionally, short-read sequencing data from a previous draft genome study revealed the presence of the mitochondrial genome of Heterodera filipjevi. Comparative analyses of Heterodera mitogenomes revealed conserved protein-coding genes essential for oxidative phosphorylation, as well as gene rearrangements and variations in transfer RNA placement, which may reflect adaptations to parasitic lifestyles. The consistently high A+T content and strand asymmetry observed across species align with trends reported in related genera. This study demonstrates the utility of long-read sequencing for identifying coexisting nematode species in agricultural fields, providing a rapid, accurate, and comprehensive alternative to traditional diagnostic methods. By incorporating non-target endemic species into public databases, this approach enhances biodiversity records and informs biosecurity strategies. These findings reinforce the potential of mitochondrial genomics to strengthen Australia's as well as the global biosecurity framework against plant-parasitic nematode threats.
PMID:40137719 | DOI:10.3390/pathogens14030234
Recent updates from <em>BNF</em> (<em>BNF 89</em>)
Drug Ther Bull. 2025 Mar 26:dtb-2025-000012. doi: 10.1136/dtb.2025.000012. Online ahead of print.
ABSTRACT
The BNF is jointly published by the Royal Pharmaceutical Society and BMJ. BNF is published in print twice a year and interim updates are issued and published monthly in the digital versions. The following summary provides a brief description of some recent key changes that have been made to BNF content.
PMID:40139730 | DOI:10.1136/dtb.2025.000012
Enhancing Care Through a Virtual Canadian Community of Practice for Managing Immune-Related Adverse Events
Curr Oncol. 2025 Feb 27;32(3):140. doi: 10.3390/curroncol32030140.
ABSTRACT
The advent of immune checkpoint inhibitors (ICIs) has significantly transformed cancer treatment outcomes. However, these therapies can induce immune-related adverse events (irAEs) that may affect any organ system, sometimes requiring specialized expertise. As ICIs are increasingly used across various tumor types and in earlier treatment settings, not all practitioners have the necessary support network to handle complex irAEs. To address this gap, we collaborated with ONCOassist, a leading app for oncology professionals, to establish the first virtual Canadian Community of Practice (CoP) focused on irAEs. The CoP facilitates continuous learning and improves patient care among Canadian clinicians treating patients with immunotherapy by providing a platform for knowledge exchange and peer-to-peer support. This article outlines the development and growth of the CoP on irAEs, highlighting both successes and challenges. As of May 2024, over a year since its inception, the CoP on irAEs has attracted almost 130 Canadian oncology healthcare professionals, and peer-to-peer interactions and engagement continue to increase. To ensure its long-term sustainability, we plan to evolve and adapt the CoP to meet the needs of the oncology community and address clinical challenges associated with new therapies.
PMID:40136344 | DOI:10.3390/curroncol32030140
Drug repurposing for non-small cell lung cancer by predicting drug response using pathway-level graph convolutional network
J Bioinform Comput Biol. 2025 Mar 25:2550001. doi: 10.1142/S0219720025500015. Online ahead of print.
ABSTRACT
Drug repurposing is the process of identifying new clinical indications for an existing drug. Some of the recent studies utilized drug response prediction models to identify drugs that can be repurposed. By representing cell-line features as a pathway-pathway interaction network, we can better understand the connections between cellular processes and drug response mechanisms. Existing deep learning models for drug response prediction do not integrate known biological pathway-pathway interactions into the model. This paper presents a drug response prediction model that applies a graph convolution operation on a pathway-pathway interaction network to represent features of cancer cell-lines effectively. The model is used to identify potential drug repurposing candidates for Non-Small Cell Lung Cancer (NSCLC). Experiment results show that the inclusion of graph convolutional model applied on a pathway-pathway interaction network makes the proposed model more effective in predicting drug response than the state-of-the-art methods. Specifically, the model has shown better performance in terms of Root Mean Squared Error, Coefficient of Determination, and Pearson's Correlation Coefficient when applied to the GDSC1000 dataset. Also, most of the drugs that the model predicted as top candidates for NSCLC treatment are either undergoing clinical studies or have some evidence in the PubMed literature database.
PMID:40134346 | DOI:10.1142/S0219720025500015
Repurposing of nervous system drugs for cancer treatment: recent advances, challenges, and future perspectives
Discov Oncol. 2025 Mar 26;16(1):396. doi: 10.1007/s12672-025-02067-4.
ABSTRACT
The nervous system plays a critical role in developmental biology and oncology, influencing processes from ontogeny to the complex dynamics of cancer progression. Interactions between the nervous system and cancer significantly affect oncogenesis, tumor growth, invasion, metastasis, treatment resistance, inflammation that promotes tumors, and the immune response. A comprehensive understanding of the signal transduction pathways involved in cancer biology is essential for devising effective anti-cancer strategies and overcoming resistance to existing therapies. Recent advances in cancer neuroscience promise to establish a new cornerstone of cancer therapy. Repurposing drugs originally developed for modulating nerve signal transduction represent a promising approach to target oncogenic signaling pathways in cancer treatment. This review endeavors to investigate the potential of repurposing neurological drugs, which target neurotransmitters and neural pathways, for oncological applications. In this context, it aims to bridge the interdisciplinary gap between neurology, psychiatry, internal medicine, and oncology. By leveraging already approved drugs, researchers can utilize existing extensive safety and efficacy data, thereby reducing both the time and financial resources necessary for the development of new cancer therapies. This strategy not only promises to enhance patient outcomes but also to expand the array of available treatments, thereby enriching the therapeutic landscape in oncology.
PMID:40133751 | DOI:10.1007/s12672-025-02067-4
Drug repurposing through Biophysical Insights: Focus on Indoleamine 2,3-Dioxygenase and Tryptophan 2,3-Dioxygenase Dual Inhibitors
Cell Biochem Biophys. 2025 Mar 26. doi: 10.1007/s12013-025-01725-2. Online ahead of print.
ABSTRACT
The kynurenine pathway (KP) plays a pivotal role in dampening the immune response in many types of cancer, including TNBC. The intricate involvement of tryptophan degradation via KP serves as a critical regulator in mediating immunosuppression in the tumor microenvironment. The key enzymes that facilitate this mechanism and contribute to tumor progression are indoleamine 2,3-dioxygenase (IDO1) and tryptophan 2,3-dioxygenase (TDO). Despite attempts to use navoximod as a dual-specific inhibitor, its poor bioavailability and lack of clinical efficacy have hampered its utility. To date, no FDA-approved drugs have advanced for dual targeting of these enzymes. Therefore, this study aimed to repurpose the approved drugs from the DrugBank database as novel IDO1/TDO inhibitors. Initially, 2588 FDA-approved compounds were screened by employing molecular docking and pharmacokinetic profiling. Subsequently, methods such as MM-GBSA calculations and machine learning based analysis precisely identified 20 potential lead compounds. The resultant compounds were then assessed for various toxicity endpoints and anticancer activity. The PaccMann server revealed potent anticancer activity, with sensitivities ranging from 0.203 to 24.119 μM against MDA-MB-231 TNBC cell lines. Alongside, the interaction profile with critical residues, strongly reinforced DB06292 (Dapagliflozin) as a compelling hit candidate. Finally, the reliability of the result was corroborated through a rigorous 200 ns molecular dynamics simulation, ensuring the stable binding of the hit against the target proteins. Considering the promising outcomes, we speculate that the proposed hit compound holds strong potential for the management of TNBC.
PMID:40133710 | DOI:10.1007/s12013-025-01725-2
Drug repositioning model based on knowledge graph embedding
Sci Rep. 2025 Mar 25;15(1):10298. doi: 10.1038/s41598-025-95372-5.
ABSTRACT
Drug repositioning utilizes existing drugs for new therapeutic applications, driven by the rapid increase in disease and drug-related data. However, organizing knowledge in this field and integrating the complex and scattered data from multiple systems into a cohesive knowledge network have become urgent problems to address. In this paper, we propose a drug repositioning model based on knowledge graph embedding. The model employs multivariate relational data to embed entities and relationships in a low-dimensional vector space. It also innovatively introduces the attention mechanism into translation and bilinear models, forming new models such as Attranse, Attdismult, and Attrescal. This model's feature extraction does not rely on a single approach, instead, it integrates multiple models and combines their screening results to enhance drug screening quality. The model's effectiveness was validated using COVID-19 data, yielding results consistent with 7 clinically approved drugs for COVID-19 treatment, indicating high accuracy in identifying new drug indications. The successful application of this model to COVID-19 suggests its potential for broader use in emerging infectious diseases and complex conditions, providing valuable insights for future drug development.
PMID:40133375 | DOI:10.1038/s41598-025-95372-5
Semantic approaches for query expansion: taxonomy, challenges, and future research directions
PeerJ Comput Sci. 2025 Mar 5;11:e2664. doi: 10.7717/peerj-cs.2664. eCollection 2025.
ABSTRACT
The internet has been inundated with an ocean of information, and hence, information retrieval systems are failing to provide optimal results to the user. In order to meet the challenge, query expansion techniques have emerged as a game-changer and are improving the results of information retrieval significantly. Of late, semantic query expansion techniques have attracted increased interest among researchers since these techniques offer more pertinent and practical results to the users. These allow the user to retrieve more meaningful and useful information from the web. Currently, few research works provide a comprehensive review on semantic query expansion; usually, they cannot provide a full view on recent advances, diversified data application, and practical challenges. Therefore, it is imperative to go deep in review in order to explain these advances and assist researchers with concrete insights for future development. This article represents the comprehensive review of the query expansion methods, with a particular emphasis on semantic approaches. It overviews the recent frameworks that have been developed within a period of 2015-2024 and reviews the limitations of each approach. Further, it discusses challenges that are inherent in the semantic query expansion field and identifies some future research directions. This article emphasizes that the linguistic approach is the most effective and flexible direction for researchers to follow, while the ontology approach better suits domain-specific search applications. This, in turn, means that development of the ontology field may further open new perspectives for semantic query expansion. Moreover, by employing artificial intelligence (AI) and making most of the query context without relying on user intervention, improvements toward the optimal expanded query can be achieved.
PMID:40134880 | PMC:PMC11935759 | DOI:10.7717/peerj-cs.2664
Psychiatric Genetics in Clinical Practice: Essential Knowledge for Mental Health Professionals
Am J Psychiatry. 2025 Mar 26:appiajp20240295. doi: 10.1176/appi.ajp.20240295. Online ahead of print.
ABSTRACT
OBJECTIVE: The authors provide recommendations on incorporating recent advances in psychiatric genetics into clinical practice for mental health clinicians.
METHOD: The International Society for Psychiatric Genetics Education Committee met monthly to come to a consensus on priority topics in psychiatric genetics. Topics were then assigned to small teams of subspecialty experts to summarize the current knowledge base and create an illustrative clinical case. Topics included, familial aggregation, common and rare genetic variants, epigenetics, gene-environment interactions, pharmacogenomics, genetic counseling, and ethical and social implications. Each section was reviewed and revised by all committee members and then finalized by the Committee Chair.
RESULTS: Key findings highlight the importance of understanding the genetic architecture of psychiatric disorders, the potential applications of genetic information in risk assessment, diagnosis, treatment selection, and patient education, as well as the ethical and social considerations surrounding the use of genetic data. The committee emphasizes the need for a nuanced approach that integrates genetic factors with environmental and experiential factors in a holistic model of care.
CONCLUSION: As psychiatric genetics continues to evolve rapidly, mental health clinicians must stay informed about the latest findings and their clinical implications. Ongoing education, collaboration with genetics professionals, and effective communication strategies are crucial to harness the power of genetics while avoiding potential pitfalls such as genetic determinism and stigma. The committee recommends a balanced perspective that recognizes the complex interplay of genetic and non-genetic factors in shaping mental health outcomes.
PMID:40134266 | DOI:10.1176/appi.ajp.20240295
Leveraging large-scale biobank EHRs to enhance pharmacogenetics of cardiometabolic disease medications
Nat Commun. 2025 Mar 25;16(1):2913. doi: 10.1038/s41467-025-58152-3.
ABSTRACT
Electronic health records (EHRs) coupled with large-scale biobanks offer great promises to unravel the genetic underpinnings of treatment efficacy. However, medication-induced biomarker trajectories stemming from such records remain poorly studied. Here, we extract clinical and medication prescription data from EHRs and conduct GWAS and rare variant burden tests in the UK Biobank (discovery) and the All of Us program (replication) on ten cardiometabolic drug response outcomes including lipid response to statins, HbA1c response to metformin and blood pressure response to antihypertensives (N = 932-28,880). Our discovery analyses in participants of European ancestry recover previously reported pharmacogenetic signals at genome-wide significance level (APOE, LPA and SLCO1B1) and a novel rare variant association in GIMAP5 with HbA1c response to metformin. Importantly, these associations are treatment-specific and not associated with biomarker progression in medication-naive individuals. We also found polygenic risk scores to predict drug response, though they explained less than 2% of the variance. In summary, we present an EHR-based framework to study the genetics of drug response and systematically investigated the common and rare pharmacogenetic contribution to cardiometabolic drug response phenotypes in 41,732 UK Biobank and 14,277 All of Us participants.
PMID:40133288 | DOI:10.1038/s41467-025-58152-3
Personalised CFTR Modulator Treatment Initiation and Monitoring in CF-Related Liver Disease: When Less Is More
Respirol Case Rep. 2025 Mar 24;13(3):e70146. doi: 10.1002/rcr2.70146. eCollection 2025 Mar.
ABSTRACT
Hepatotoxicity due to Elexacaftor/Tezacaftor/Ivacaftor (ETI) use has been well documented. There are no dose adjustments or increased-frequency monitoring algorithms recommended for people who experience elevated transaminases without cirrhosis, only suggested treatment interruption or withdrawal depending on the severity of the derangement. Here we describe a patient with non-cirrhotic hepatic steatosis who experienced persistently elevated liver function tests due to modulator therapy but demonstrated a remarkable response to a notably low dose of ETI.
PMID:40134928 | PMC:PMC11932953 | DOI:10.1002/rcr2.70146
Hydrogel-Based Tumor Tissue Microarchitecture Reshapes Dendritic Cell Metabolic Profile and Functions
Adv Healthc Mater. 2025 Mar 26:e2500681. doi: 10.1002/adhm.202500681. Online ahead of print.
ABSTRACT
The extracellular matrix (ECM) plays a pivotal role in immunomodulation, providing structural and biochemical cues that shape immune cell function. In pathological conditions like cancer and chronic inflammation, dysregulated remodeling often results in altered ECM composition and architecture, with fibrillar alignment being a hallmark linked to disease progression. Here, how ECM alignment influences dendritic cell (DC) behavior using 3D biomimetic collagen matrices with controlled fibril anisotropy is investigated. This results show that immature DCs in aligned matrices exhibited increased expression of CD86 and HLA-DR with elevated secretion of CXCL8 and CCL2 chemokines, which may enhance immune cell recruitment. However, transcriptomic and metabolomic analysis revealed significant downregulation of oxidative phosphorylation and an insufficient compensatory shift toward glycolysis, resulting in reduced ATP production. This metabolic constraint correlated with impaired/reduced DC migratory speed and distance. In contrast, mature DCs displayed minimal sensitivity to ECM alignment, maintaining uniform differentiation and functional profiles across matrix conditions. T-cell coculture experiments revealed that ECM alignment dampens T-cell activation and proliferation, likely through direct modulation of T-cell behavior. These findings highlight the stage-specific effects of ECM alignment on DC function, highlighting its role in DC immunomodulation, with implications for therapeutic development in cancer and other pathological contexts.
PMID:40134371 | DOI:10.1002/adhm.202500681
Transmission dynamics of the 2022 mpox epidemic in New York City
Nat Med. 2025 Mar 25. doi: 10.1038/s41591-025-03526-9. Online ahead of print.
ABSTRACT
The 2022 global mpox epidemic was caused by transmission of MPXV clade IIb, lineage B.1 through sexual contact networks, with New York City (NYC) experiencing the first and largest outbreak in the United States. By performing phylogeographic analysis of MPXV genomes sampled from 757 individuals in NYC between April 2022 and April 2023, and 3,287 MPXV genomes sampled around the world, we identify over 200 introductions of MPXV into NYC with at least 84 leading to onward transmission. These infections primarily occurred among men who have sex with men, transgender women and nonbinary individuals. Through a comparative analysis with HIV in NYC, we find that both MPXV and HIV genomic cluster sizes are best fit by scale-free distributions, and that people in MPXV clusters are more likely to have previously received an HIV diagnosis and be a member of a recently growing HIV transmission cluster. We model MPXV transmission through sexual contact networks and show that highly connected individuals would be disproportionately infected at the start of an epidemic, which would likely result in the exhaustion of the most densely connected parts of the network, and, therefore, explain the rapid expansion and decline of the NYC outbreak. By coupling the genomic epidemiology of MPXV and HIV with epidemic modeling, we demonstrate that the transmission dynamics of MPXV in NYC can be understood by general principles of sexually transmitted pathogens.
PMID:40133528 | DOI:10.1038/s41591-025-03526-9
Enzymatic cleavage of model lignin dimers depends on pH, enzyme, and bond type
Sci Rep. 2025 Mar 25;15(1):10296. doi: 10.1038/s41598-025-88571-7.
ABSTRACT
Lignin is composed of phenylpropanoid monomers linked by ether and carbon-carbon bonds to form a complex heterogeneous structure. Bond-specific studies of lignin-modifying enzymes (LMEs; e.g., laccases and peroxidases) are limited by the polymerization of model lignin substrates and repolymerization of cleavage products. Here we present a high throughput platform to screen LME activities on four tagged model lignin compounds that represent the β-O-4', β-β', 5-5', and 4-O-5' linkages in lignin. We utilized nanostructure-initiator mass spectrometry (NIMS) and model lignin compounds with tags containing perfluorinated and cationic moieties, which effectively limit polymerization and condensation of the substrates and their degrading products. Sub-microliter sample droplets were printed on the NIMS chip with a novel robotics method. This rapid platform enabled characterization of LMEs across a range of pH 3-10 and relative quantification of modified (typically oxidized), cleaved, and polymerized products. All tested enzymes oxidized the four substrates and cleaved the β-O-4' and β-β' substrates to monomeric products. We discovered that the active pH range depended on both the substrate and the enzyme type. This has important applications for biomass conversion to biofuels and bioproducts, where the relative percentages of different bond types in lignin varies depending on feedstock and chemical pretreatment methods.
PMID:40133407 | DOI:10.1038/s41598-025-88571-7
Identification of neutralizing nanobodies protecting against poxvirus infection
Cell Discov. 2025 Mar 25;11(1):31. doi: 10.1038/s41421-025-00771-7.
ABSTRACT
An outbreak of mpox has triggered concerns regarding the adequacy of intervention strategies. Passive immunity conferred by neutralizing antibodies exhibits potential in the prophylaxis and treatment of orthopoxvirus infections. Despite this, the investigations of effective antibody therapeutics have been hindered by the varied nature of orthopoxvirus envelope proteins and the intricate mechanisms underpinning viral invasion. Our study involves the production of six mpox virus (MPXV) envelope proteins, which are relatively conservative and considered to play a role in the neutralization process. We employed a synthetic nanobody (Nb) library to derive a broad array of specific Nbs against these viral proteins. We identified a cross-reactive Nb, termed M1R-01, which targets the M1R protein and effectively neutralizes both vaccinia virus (VACV) and MPXV. Notably, the M1R-01-based antibody strategy provided optimal protection against a lethal VACV challenge in mice. Additionally, we determined the crystal structure of the M1R-Nb complex, uncovering novel binding attributes of M1R-01 and detailed conformational epitope information. This work provides a promising candidate for the therapy and prophylaxis of orthopoxvirus infections.
PMID:40133273 | DOI:10.1038/s41421-025-00771-7
The ER-phagy receptor FAM134B is targeted by Salmonella Typhimurium to promote infection
Nat Commun. 2025 Mar 25;16(1):2923. doi: 10.1038/s41467-025-58035-7.
ABSTRACT
Macroautophagy/autophagy is a key catabolic-recycling pathway that can selectively target damaged organelles or invading pathogens for degradation. The selective autophagic degradation of the endoplasmic reticulum (hereafter referred to as ER-phagy) is a homeostatic mechanism, controlling ER size, the removal of misfolded protein aggregates, and organelle damage. ER-phagy can also be stimulated by pathogen infection. However, the link between ER-phagy and bacterial infection remains poorly understood, as are the mechanisms evolved by pathogens to escape the effects of ER-phagy. Here, we show that Salmonella enterica serovar Typhimurium inhibits ER-phagy by targeting the ER-phagy receptor FAM134B, leading to a pronounced increase in Salmonella burden after invasion. Salmonella prevents FAM134B oligomerization, which is required for efficient ER-phagy. FAM134B knock-out raises intracellular Salmonella number, while FAM134B activation reduces Salmonella burden. Additionally, we found that Salmonella targets FAM134B through the bacterial effector SopF to enhance intracellular survival through ER-phagy inhibition. Furthermore, FAM134B knock-out mice infected with Salmonella presented severe intestinal damage and increased bacterial burden. These results provide mechanistic insight into the interplay between ER-phagy and bacterial infection, highlighting a key role for FAM134B in innate immunity.
PMID:40133256 | DOI:10.1038/s41467-025-58035-7
Fuzheng Huayu tablets for treating pulmonary fibrosis in post-COVID-19 patients: a multicenter, randomized, double-blind, placebo-controlled trial
Front Pharmacol. 2025 Mar 11;16:1508276. doi: 10.3389/fphar.2025.1508276. eCollection 2025.
ABSTRACT
BACKGROUND: Effective therapies for pulmonary fibrosis caused by coronavirus disease (COVID-19) and other etiologies are lacking. Our previous studies demonstrated that Fuzheng Huayu tablet (FZHY), a traditional Chinese medicine known for its anti-liver fibrotic properties, can improve lung function in patients with chronic obstructive pulmonary disease and attenuate bleomycin-induced pulmonary fibrosis in rats.
PURPOSE: This study aimed to evaluate the efficacy and safety of FZHY in post-COVID-19 pulmonary fibrosis.
METHODS: A multi-center, randomized, double-blind, placebo-controlled clinical trial was conducted to evaluate the efficacy of a 24-week treatment with FZHY, combined with vitamin C and respiratory function rehabilitation, for treating pulmonary fibrosis in discharged convalescent COVID-19 patients. The primary outcome was the regression rate of pulmonary fibrosis assessed by the high-resolution computed tomography scores and lung function improvement (forced vital capacity [FVC], forced expiratory volume in one second [FEV1], and FEV1/FVC) after 24 weeks. Secondary outcomes included the 6-min walk distance, improvement in pulmonary inflammation, clinical symptoms, and quality of life.
RESULTS: This study included 142 patients, who were randomized to the FZHY (n = 72) and placebo groups (n = 70). By week 24, the regression rates of pulmonary fibrosis in the FZHY and placebo groups were 71.2% and 49.2%, respectively (p = 0.01). Limited spirometry data revealed higher FEV1/FVC in the FZHY group than in the placebo group at week 8 ([87.7 ± 7.2] % vs. [82.7 ± 6.9] %; p = 0.018). The regression rates in pulmonary inflammation in the FZHY and placebo groups were 83.8% and 68.8%, respectively (p = 0.04). At week 4, the increase in 6-min walking distance was greater in the FZHY group than in the placebo group ([41.4 ± 64.1] m vs. [21.8 ± 50.3] m; p = 0.05). However, no significant differences were observed between the groups in the improvement rate of clinical symptoms, quality of life-BREF, patient health questionnaire-9, or generalized anxiety disorder-7 scores (p > 0.05). No drug-related adverse events were reported in the FZHY group.
CONCLUSION: FZHY attenuates post-COVID-19 pulmonary fibrosis, with good safety profiles.
CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/study/NCT04279197, identifier NCT04279197.
PMID:40135237 | PMC:PMC11933019 | DOI:10.3389/fphar.2025.1508276
Sevoflurane-Associated Acute Liver Injury in Renal Transplantation and Review of Literature
Case Rep Anesthesiol. 2025 Mar 18;2025:1303993. doi: 10.1155/cria/1303993. eCollection 2025.
ABSTRACT
Acute liver injury can be precipitated by several factors perioperatively. One of the rare factors identified intraoperatively is the use of sevoflurane, an inhalational anesthetic agent which can cause significant acute hepatotoxicity. The report presents a case of acute liver injury followed by graft loss in a patient who underwent kidney transplantation. The patient developed several complications which resulted in graft loss. Close postoperative monitoring of patients following kidney transplantation is crucial. The case supports the current literature describing sevoflurane as a hepatotoxic agent. Medication side effects should be closely monitored both intraoperatively and postoperatively in those with renal dysfunction.
PMID:40134944 | PMC:PMC11936524 | DOI:10.1155/cria/1303993
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