Front Cell Infect Microbiol. 2025 Jul 9;15:1539240. doi: 10.3389/fcimb.2025.1539240. eCollection 2025.

ABSTRACT

Tuberculosis (TB) remains a major global health threat, with the urgent need for rapid and accurate diagnostic methods to improve control and treatment outcomes. This study evaluates the performance of MassARRAY technology for detecting Mycobacterium tuberculosis (MTB) and identifying drug resistance, compared to traditional culture methods and Xpert MTB/RIF. From July 2021 to February 2024, bronchoalveolar lavage fluid (BALF) samples from 289 suspected pulmonary tuberculosis patients at Henan Provincial Chest Hospital, China, were tested using MassARRAY, Xpert MTB/RIF, and conventional culturing techniques. The performance of each method was assessed for MTB detection, and the ability of MassARRAY to identify drug resistance was compared with standard drug susceptibility testing (DST). MassARRAY demonstrated a sensitivity of 96.5% and a specificity of 34.6% for MTB detection, outperforming the Xpert MTB/RIF assay in sensitivity (94.7%) but showing lower specificity. In detecting rifampicin resistance, MassARRAY achieved concordance rates of 83.93% with Xpert MTB/RIF and 72.73% with DST. Furthermore, MassARRAY successfully identified key genetic mutations associated with drug resistance, such as rpoB 531 for rifampicin and katG 315 for isoniazid. MassARRAY demonstrated high concordance with DST for several drugs, including isoniazid, kanamycin, and streptomycin, but exhibited limitations in detecting resistance to pyrazinamide, clofazimine, cycloserine, and linezolid. Overall, MassARRAY provides a rapid, cost-effective, and high-throughput diagnostic platform for MTB and drug resistance, particularly for first-line anti-tuberculosis drugs. While limitations in specificity and resistance detection for certain second-line drugs exist, its ability to rapidly provide comprehensive resistance profiles makes it a valuable tool for TB management.

PMID:40703669 | PMC:PMC12283603 | DOI:10.3389/fcimb.2025.1539240

Evol Appl. 2025 Jul 23;18(7):e70138. doi: 10.1111/eva.70138. eCollection 2025 Jul.

ABSTRACT

Maternally transmitted symbionts such as Wolbachia spread within host populations by mediating reproductive phenotypes. Cytoplasmic incompatibility (CI) is a reproductive phenotype that interferes with embryonal development when infected males fertilize uninfected females. Wolbachia-based pest control relies on strong CI to suppress or replace pest populations. Host genetic background determines CI strength, and host suppressors that cause weak CI threaten the efficacy of Wolbachia-based pest control programs. In haplodiploids, CI embryos either die (Female Mortality, FM-CI) or develop into uninfected males (Male Development, MD-CI). The reciprocal spread of host suppressors and infection, as well as the interaction with the two CI outcomes in haplodiploids, remains poorly understood. The contribution of sex allocation distortion (Sd), an independent Wolbachia-mediated reproductive phenotype that causes a female-biased sex ratio, to infection persistence in haplodiploids is also poorly understood, especially with imperfect maternal transmission. To address these issues, we developed individual-based simulations and validated this computational tool by tracking Wolbachia spread in experimental Tetranychus urticae populations and by contrasting infection dynamics with deterministic mathematical models. Within ⁓14 host generations, we found that deterministic models inflate infection frequencies relative to simulations by ⁓8.1% and overestimate the driving potential of CI, particularly under low initial infection frequencies. Compared to MD-CI, we show that FM-CI strongly extends infection persistence when nuclear suppressors are segregating in the population. We also quantify how maternal transmission modulates the reciprocal spread of suppressors and infection. Upon loss of CI, we show that hypomorphic expression of Sd (~5%) is sufficient for a stable persistence of infection. We derive a mathematical expression that approximates the stable polymorphic infection frequencies that can be maintained by Sd. Collectively, our results advance our understanding of how symbiosis with CI-inducing Wolbachia and haplodiploid hosts might evolve and inform CI-based pest control programs of potential future risks.

PMID:40703634 | PMC:PMC12284905 | DOI:10.1111/eva.70138

Front Immunol. 2025 Jul 9;16:1596113. doi: 10.3389/fimmu.2025.1596113. eCollection 2025.

ABSTRACT

Hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS) are life-threatening hyperinflammatory conditions. Primary HLH is caused by genetic mutations associated with defective cytotoxicity, while secondary HLH is triggered by various factors, including infection-associated HLH (IAHS), rheumatic diseases-associated HLH (MAS), or malignancy-associated HLH (M-HLH). We retrospectively reviewed the medical records of patients younger than 20 years of age with physician-diagnosed HLH or MAS between January 2005 and July 2022 in a large medical center in Taiwan. Seven patients were prospectively enrolled since Jan 2019. Clinical and laboratory features, treatments rendered, and outcomes of patients with HLH/MAS were analyzed. Fifty-two patients with HLH/MAS were included in this study and classified as follows: 21 (40.4%) with IAHS, 20 (38.5%) with MAS, 5 (9.6%) with M-HLH, 4 (7.7%) with primary HLH, and 2 (3.8%) with unclassified HLH (U-HLH). The median age of diagnosis for all patients was 9.04 years, while it ranged between 5.12 (for primary HLH) to 16.03 (for M-HLH) years. Two-year probabilities of survival of each group of HLH/MAS were 100%, 85.7%, 65.63%, 25%, and 20% for patients with U-HLH, IAHS, MAS, primary HLH, and M-HLH, respectively (log-rank, P =0.0018). The five-year probability of survival was 65.63% for patients with MAS. M-HLH and ICU admission were significantly associated with mortality. Infections and rheumatic diseases are the main triggers or conditions associated with pediatric HLH/MAS, whereas malignancy is an important etiology among adolescents.

PMID:40703525 | PMC:PMC12284797 | DOI:10.3389/fimmu.2025.1596113

iScience. 2025 Jun 28;28(8):113031. doi: 10.1016/j.isci.2025.113031. eCollection 2025 Aug 15.

ABSTRACT

For cancer patients, metastasis is a life-threatening event limiting therapeutic options. Molecularly, the metastatic phenotype can be conferred by mitochondrial reactive oxygen species (mtROS) generated upon metabolic stress. Mitochondrial damage can also trigger mtROS production, which is particularly well illustrated for anthracyclines. Here, we tested in mouse models of murine and human breast cancer whether this type of chemotherapy can trigger metastasis. We report that subcytotoxic doses of doxorubicin mimicking the clinical situation in poorly perfused tumor areas sequential trigger mtROS production, activate TGFβ pathway effector Pyk2, and increase cancer cell migration and invasion. Fortunately, the metastatic switch was incompletely induced, and doxorubicin did not promote breast cancer metastasis in immunocompetent mice. Yet, MitoTEMPO fully prevented metastatic dissemination and did not interfere with doxorubicin cytotoxicity, making it attractive to combine anthracyclines with mitochondria-targeted antioxidants.

PMID:40703453 | PMC:PMC12283550 | DOI:10.1016/j.isci.2025.113031

iScience. 2025 Jun 28;28(8):113038. doi: 10.1016/j.isci.2025.113038. eCollection 2025 Aug 15.

ABSTRACT

Preterm infants are frequently administered antibiotics to prevent infections, yet their impact on the developing gut microbiota and metabolome remains complex and clinically significant. To systematically assess these effects, we analyzed longitudinal stool samples from 54 extremely- and very-low-birthweight infants by integrating clinical data, 16S rRNA-based microbiome profiling, targeted metabolomics, and community-scale metabolic modeling. Antibiotic exposure disrupted microbial diversity, depleted beneficial taxa, and altered metabolites such as short-chain fatty acids (SCFAs) and bile acids. Class-specific antibiotic effects were observed, with cephalosporins promoting Staphylococcus dominance and potentially reducing bile acid diversity. Necrotizing enterocolitis (NEC) samples showed SCFAs depletion and enrichment of antibiotic-resistant genera. In silico models further identified microbial contributors to SCFAs production and recapitulated metabolite trends. These findings demonstrate how antibiotic regimens can perturb the neonatal gut ecosystem and highlight the need for precision antibiotic stewardship to preserve microbiome-derived metabolic functions and reduce disease risk in preterm infants.

PMID:40703452 | PMC:PMC12283561 | DOI:10.1016/j.isci.2025.113038

Front Microbiol. 2025 Jul 9;16:1582121. doi: 10.3389/fmicb.2025.1582121. eCollection 2025.

ABSTRACT

INTRODUCTION: Elizabethkingia miricola is a gram-negative bacterium that causes life-threatening infections in vulnerable populations. Unlike other species in the Elizabethkingia genus, E. miricola also leads to meningitis-like diseases in aquatic invertebrates such as frogs, raising concerns about its zoonotic transmission potential. Management of its infection is complicated by unclear transmission pathways and multi-drug resistance.

METHODS: In this study, we analyzed three clinical strains (E. miricola Mich-1, Mich-2, and Mich-3) isolated from patients in Michigan using morphology observations, biochemical tests, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-ToF/MS), and genome sequencing.

RESULTS: Average Nucleotide Identity (ANI) analysis revealed that the Michigan strains were nearly identical and shared 96.52% identity with the type strain E. miricola DSM 14571, confirming their classification as E. miricola. Comprehensive comparative genomic analyses were conducted across 28 strains, including human isolates and strains from invertebrates like frogs. The strains exhibited open pan-genome characteristics. Mich-1 shared 3,199 genes (83.2%) with human isolates but fewer genes with frog-derived isolates (ranging from 3,319 to 3,375). This phylogenetic analysis highlights regional variation and the global diversity of E. miricola isolates, revealing connections between clinical and environmental strains. Antibiotic susceptibility testing revealed that the three clinical strains were resistant to 13 out of 16 tested drugs, with susceptibility only to trimethoprim/sulfamethoxazole and ciprofloxacin. The strains carried five β-lactamase-encoding genes (BlaB-10, BlaB-39, CME-1, CME-2, and GOB-25), conferring resistance to penams, cephalosporins, and carbapenems. Several virulence-associated genes were conserved across clinical and frog isolates. These genes contribute to stress adaptation, adherence, and immune modulation.

DISCUSSION: This study underscores the evolutionary adaptability of E. miricola genomes, highlighting their capacity to acquire genetic traits that enable survival in diverse niches. This adaptability facilitates the emergence of more resistant and virulent strains, posing significant threats to both human and animal health.

PMID:40703244 | PMC:PMC12283610 | DOI:10.3389/fmicb.2025.1582121

Comput Struct Biotechnol J. 2025 Jul 10;27:3079-3089. doi: 10.1016/j.csbj.2025.07.009. eCollection 2025.

ABSTRACT

This study presents the development and validation of a liquid chromatography-quadrupole-time-of-flight mass spectrometry method with data-independent acquisition (LC-QTOF-MSE) for targeted quantification, post-targeted screening, and untargeted metabolite profiling. Using MS1-based precursor ion quantification, the method demonstrated excellent analytical performance with linearity (R² > 0.99), accuracy (84 %-131 %), and precision (1 %-17 % relative standard deviation (RSD)). Although LC-QTOF‑MSE sensitivity is at least nine-fold lower than LC-triple quadrupole MS with multiple reaction monitoring, it remains adequate for quantifying urinary metabolites, particularly those that fragment poorly or yield low‑intensity product ions. For post‑targeted screening and untargeted profiling, an in‑house reference library (the Siriraj Metabolomics Data Warehouse, SiMD), comprising 174 curated metabolite standards, was integrated into the workflow to enhance metabolite identification confidence. The official website for SiMD can be accessed at https://si-simd.com/. To demonstrate the method's utility, 11 amino and organic acids were quantified in urine samples from 100 healthy individuals. Four compounds-L-methionine, L-histidine, L-tryptophan, and trans-ferulic acid-were significantly higher levels in females (P < 0.05), likely reflecting sex-specific physiological or dietary intake differences. Post‑targeted screening identified 29 additional metabolites and assigned them to level 1 (m/z, RT, isotope pattern, and MS/MS spectra matched to reference standards) based on the Metabolomics Standards Initiative guidelines. Untargeted retrospective profiling revealed level 1 seven metabolites, including ribitol, creatine, glucuronic acid, trans-ferulic acid, succinic acid, dimethylglycine, and 3-hydroxyphenylacetic acid related to sex variation (VIP > 1.5). In summary, the LC-QTOF-MSE method coupled with SiMD provides a robust and comprehensive workflow for metabolomics analysis. It enables reliable target quantification and enhances confidence in metabolite identification while also reducing sample and instrumental demands. These features make it particularly well-suited for clinical metabolomics studies.

PMID:40703097 | PMC:PMC12284563 | DOI:10.1016/j.csbj.2025.07.009

Br J Pharmacol. 2025 Jul 24. doi: 10.1111/bph.70129. Online ahead of print.

ABSTRACT

Addressing complexity in the study of life sciences through Systems Biology and Systems Medicine has been transformative, making Systems Pharmacology the next logical step. In this review, we focus on physical stimuli, whose potential in pharmacology has been neglected, despite demonstrated therapeutic properties. To address this overlooked aspect of pharmacology, we aim to (i), highlight how physical stimuli (mechanical, optical, magnetic, electrical) influence inflammation; (ii) identify known overlaps among transduction mechanisms of physical stimuli and highlight the need for deeper understanding of these mechanisms; (iii) promote advanced network approaches as tools to understand this complexity and enhance the potential of anti-inflammatory physical therapies; and (iv), integrate physical stimuli into the mindset of pharmacologists. The overall purpose of this review is to spark questions rather than provide answers, and to drive research in this critically underexplored area.

PMID:40702933 | DOI:10.1111/bph.70129

Br J Pharmacol. 2025 Jul 23. doi: 10.1111/bph.70133. Online ahead of print.

ABSTRACT

BACKGROUND AND PURPOSE: Thiamine (vitamin B1) is an essential coenzyme and catalyses various reactions in central metabolic pathways. Since mammals have lost the ability to synthesise thiamine de novo, this micronutrient has to be imported via the high affinity solute carriers SLC19A2 and A3 across the plasma membrane. Perturbations of these transport systems have severe effects on human health. Recent structural work on SLC19A2 and A3 have provided molecular insights into substrate and drug recognition and conformational changes during transport. Based on the analysis of the available SLC19A3 structures, we hypothesise that the binding site is rather promiscuous, allowing different small molecules to interact and potentially inhibit this transporter.

EXPERIMENTAL APPROACH: We employed a computational approach, by which 538 approved and investigational drugs were docked into an ensemble of SLC19A3 cryo-EM structures, followed by experimental binding studies, transport inhibition assays, and structural validation.

KEY RESULTS: Eight novel compounds were identified that bind and inhibit SLC19A3. To visualise such a new drug interaction, we determined the cryo-EM structure of SLC19A3 bound to domperidone, a dopamine D2 receptor antagonist used for the treatment of nausea and gastrointestinal disorders. Our computational work together with biochemical and cellular transport assays expands the understanding of SLC19A3-drug interactions, highlights the power of virtual screening approaches using structural ensembles, and provides a three-dimensional pharmacophore model for SLC19A3 inhibitors.

CONCLUSION AND IMPLICATIONS: These findings offer a basis for addressing drug-induced thiamine deficiencies and pre approach can be used to optimise pharmacological strategies involving SLC19A3-interacting compounds in the future.

PMID:40702645 | DOI:10.1111/bph.70133

Genome Biol. 2025 Jul 23;26(1):219. doi: 10.1186/s13059-025-03682-8.

ABSTRACT

Biological insights often depend on comparing conditions such as disease and health. Yet, we lack effective computational tools for integrating single-cell genomics data across conditions or characterizing transitions from normal to deviant cell states. Here, we present Decipher, a deep generative model that characterizes derailed cell-state trajectories. Decipher jointly models and visualizes gene expression and cell state from normal and perturbed single-cell RNA-seq data, revealing shared and disrupted dynamics. We demonstrate its superior performance across diverse contexts, including in pancreatitis with oncogene mutation, acute myeloid leukemia, and gastric cancer.

PMID:40702544 | DOI:10.1186/s13059-025-03682-8

eNeuro. 2025 Jul 23;12(7):ENEURO.0410-20.2025. doi: 10.1523/ENEURO.0410-20.2025. Print 2025 Jul.

ABSTRACT

The development of Schwann cells, which myelinate axons in the peripheral nervous system, is critically dependent on MEK/ERK signaling. While Ets-domain transcription factors (Etv1, Etv4, Etv5) are downstream effectors of this pathway, only Etv1 has been specifically linked to Schwann cell development. Here, we examined the functions of Etv5, which is expressed in Schwann cell precursors, neural crest cells and satellite glia, at embryonic stages and at low levels in mature Schwann cells. In hypomorphic Etv5tm1Kmm homozygous mutant mice, no overt defects in Schwann cell differentiation were observed at embryonic stages. To study the function of Etv5 in juvenile (postnatal days 21-30) and mature adult (6 month) mice, we generated Etv5 conditional knock-outs (cKOs) using a Sox10-Cre driver. In juvenile male Etv5-cKO mice, Schwann cell numbers increased normally after a peripheral nerve crush injury, a response that was attenuated by 6 months. Transmission electron microscopy of the naive sciatic nerve revealed a decline in axonal diameter and perturbed myelination in Etv5-cKO male and female mice. The innervated gastrocnemius muscle declined in area and volume in Etv5-cKO mice of both sexes, suggesting nerve structural abnormalities cause muscle atrophy. However, control and Etv5-cKO male and female mice performed similarly in motor behavior tests after a crush injury. Thus, Etv5 is not essential for Schwann cell differentiation, but Etv5 plays a crucial role in the age-dependent regulation of Schwann cell function, including nerve repair and the maintenance of axonal integrity in mature peripheral nerves.

PMID:40701803 | DOI:10.1523/ENEURO.0410-20.2025

Plant Cell. 2025 Jul 23:koaf181. doi: 10.1093/plcell/koaf181. Online ahead of print.

NO ABSTRACT

PMID:40701651 | DOI:10.1093/plcell/koaf181

J Agric Food Chem. 2025 Jul 23. doi: 10.1021/acs.jafc.5c01195. Online ahead of print.

ABSTRACT

This study explores the chemical space of bitter peptides through a curated data set, named Bitter Peptide Space (BPS)-1000, which includes experimentally validated bitter and nonbitter peptides. The data set integrates sensory data, bitter taste thresholds (BTTs), and bitter taste receptor (TAS2R) activity when available. The inclusion of modified peptides further expands the data set's diversity. The HELM (Hierarchical Editing Language for Macromolecules) and BILN (Boehringer Ingelheim Line Notation) notations have been generated to provide a unique representation for both canonical and modified peptides. Through sequence-based and structure-based analyses, the study highlights the role of hydrophobicity, molecular size, and specific amino acid composition in the bitter and nonbitter sets in canonical and modified peptides, suggesting differences that could contribute to bitterness and enhancing the understanding of bitter peptide characteristics.

PMID:40701541 | DOI:10.1021/acs.jafc.5c01195

Eur J Vasc Endovasc Surg. 2025 Jul 21:S1078-5884(25)00693-8. doi: 10.1016/j.ejvs.2025.07.030. Online ahead of print.

NO ABSTRACT

PMID:40701423 | DOI:10.1016/j.ejvs.2025.07.030

Antiviral Res. 2025 Jul 21:106241. doi: 10.1016/j.antiviral.2025.106241. Online ahead of print.

ABSTRACT

Dengue virus is the most important arbovirus for public health worldwide. Aedes aegypti is the DENV primary vector and acquires the virus during blood meal from a viremic human. BCN0941 is a structure-based designed antiviral peptide that inhibits early stages of DENV infection in mammalian cells [WO2015131858A2]. Studies of structure-activity relationship indicate that the molecular target of the antiviral activity of BCN0941 is the Low-density lipoprotein receptor related protein-1 (LRP1), an evolutionary conserved receptor that we have identified as putative DENV receptor in mammalian cells. In this work, we evaluated the antiviral activity of BCN0941 peptide against DENV serotype 1 in mosquito cells. In vitro assays were performed in cell lines C6/36 (Aedes albopictus) and Aag2 (Aedes aegypti). The antiviral activity in vivo in a metapopulation of field-collected A. aegypti mosquitoes was also evaluated. BCN0941 peptide exhibited the capacity to decrease viral infection in both experimental set up, in vivo and in vitro, up to a 50% and 60% of the treatment controls respectively, as determined by immunofluorescence. BCN0941 may be an effective DENV transmission-blocking drug due to its dual action in decreasing the viral load in infected people and the mosquito vector.

PMID:40701277 | DOI:10.1016/j.antiviral.2025.106241

Mol Cell Proteomics. 2025 Jul 21:101039. doi: 10.1016/j.mcpro.2025.101039. Online ahead of print.

ABSTRACT

Antigenic noncanonical epitope and novel protein discovery are research areas with therapeutical applications, predominantly done via mass spectrometry. The latter should rely on a well-characterized proteogenomic search space. Its size is barely known for antigenic noncanonical peptides and novel proteins, and this could impact on their identification. To address these issues, we here develop an automated workflow comprised of Sequoia for the creation of RNA sequencing informed and exhaustive sequence search spaces for various noncanonical peptide origins, and SPIsnake for pre-filtering and exploration of sequence search space prior to mass spectrometry searches. We apply our workflow to characterize the exact sizes of tryptic and nonspecific peptide sequence search spaces in a variety of definitions, their reduction when using RNA expression, their inflation by post-translational modifications, and the frequency of peptide sequence multimapping to different noncanonical origins. Furthermore, we explore the application of Sequoia and SPIsnake on HLA-I immunopeptidomes, thereby rescuing sensitivity in peptide identification when confronted with inflated search spaces. Taken together, Sequoia and SPIsnake pave the way for an educated development of methods addressing large-scale exhaustive proteogenomic discovery by exposing the consequences of database size inflation and ambiguity of peptide and protein sequence identification.

PMID:40701202 | DOI:10.1016/j.mcpro.2025.101039

Dev Cell. 2025 Jul 21:S1534-5807(25)00436-8. doi: 10.1016/j.devcel.2025.06.038. Online ahead of print.

ABSTRACT

Xylem, the predominant tissue for structural support, forms tension wood with G-layer-rich fibers under mechanical stress. Despite being recognized over a century ago, three key biological questions remained unclear: (1) are fibers in normal and tension wood distinct cells due to morphological differences? (2) Do tension wood fibers arise from different lineages? (3) What are the key genes controlling tension wood formation? We conducted single-cell RNA sequencing on normal, tension and opposite xylem. Fibers in normal and tension wood belong to the same cell type and lineage. Differential developmental speed and cell-type ratio in tension and opposite xylem were further validated by spatial transcriptomics and metabolomics. Phosphoproteomics showed mechanical sensing mechanisms conserved between stems and roots across angiosperms. We identified a group of genes involved in the cell fate transition in tension wood. The knowledge on the heterogeneity of cell development offers insights into optimizing biomass production and bioenergy yield.

PMID:40701155 | DOI:10.1016/j.devcel.2025.06.038

PLoS Pathog. 2025 Jul 23;21(7):e1013282. doi: 10.1371/journal.ppat.1013282. Online ahead of print.

ABSTRACT

Trichomonas vaginalis infects the urogenital tract of men and women and causes the sexually transmitted infection trichomoniasis. Since the publication of its draft genome in 2007, the genome has drawn attention for several reasons, including its unusually large size, massive expansion of gene families, and high repeat content. The fragmented nature of the draft assembly made it challenging to obtain accurate metrics of features, such as spliceosomal introns. The number of introns identified has varied over the years, ranging from 41 when first characterized in 2005, to 32 in 2018 when the repertoire was revised. In both cases, the results suggested that more introns could be present in the genome. In this study, we exploited our new T. vaginalis G3 chromosome-scale assembly and annotation and high-coverage transcriptome datasets to provide an up-to-date repertoire of spliceosomal introns in the species. We developed a custom pipeline that distinguishes true splicing events from chimeric alignments by utilizing the extended motifs required by the splicing machinery, and experimentally verified the results using transcript evidence. We identified a total of 63 active introns and 34 putative "inactive" intron sequences in T. vaginalis, enabling an analysis of their length distribution, extended consensus motifs, intron phase distribution (including an unexpected expansion of UTR introns), and functional annotation. Notably, we found that a short intron in T. vaginalis, at only 23 nucleotides in size, is one of the shortest introns known to date. We tested our pipeline on a chromosome-scale assembly of the bird parasite Trichomonas stableri, the closest known relative to T. vaginalis. Our results revealed some conservation of the main features (total intron count, sequence, length distribution, and motifs) of these two closely related species, although differences in their functional annotation and duplication suggest alternative splicing machinery in T. vaginalis.

PMID:40700464 | DOI:10.1371/journal.ppat.1013282

Clocks Sleep. 2025 Jun 23;7(3):30. doi: 10.3390/clockssleep7030030.

ABSTRACT

Chronobiotics represent a pharmacologically diverse group of substances, encompassing both experimental compounds and those utilized in clinical practice, which possess the capacity to modulate the parameters of circadian rhythms. These substances influence fluctuations in various physiological and biochemical processes, including the expression of core "clock" genes in model organisms and cell cultures, as well as the expression of clock-controlled genes. Despite their chemical heterogeneity, chronobiotics share the common ability to alter circadian dynamics. The concept of chronobiotic drugs has been recognized for over five decades, dating back to the discovery and detailed clinical characterization of the hormone melatonin. However, the field remains fragmented, lacking a unified classification system for these pharmacological agents. The current categorizations include natural chrononutrients, synthetic targeted circadian rhythm modulators, hypnotics, and chronobiotic hormones, yet no comprehensive repository of knowledge on chronobiotics exists. Addressing this gap, the development of the world's first curated and continuously updated database of chronobiotic drugs-circadian rhythm modulators-accessible via the global Internet, represents a critical and timely objective for the fields of chronobiology, chronomedicine, and pharmacoinformatics/bioinformatics. The primary objective of this study is to construct a relational database, ChronobioticsDB, utilizing the Django framework and PostGreSQL as the database management system. The database will be accessible through a dedicated web interface and will be filled in with data on chronobiotics extracted and manually annotated from PubMed, Google Scholar, Scopus, and Web of Science articles. Each entry in the database will comprise a detailed compound card, featuring links to primary data sources, a molecular structure image, the compound's chemical formula in machine-readable SMILES format, and its name according to IUPAC nomenclature. To enhance the depth and accuracy of the information, the database will be synchronized with external repositories such as ChemSpider, DrugBank, Chembl, ChEBI, Engage, UniProt, and PubChem. This integration will ensure the inclusion of up-to-date and comprehensive data on each chronobiotic. Furthermore, the biological and pharmacological relevance of the database will be augmented through synchronization with additional resources, including the FDA. In cases of overlapping data, compound cards will highlight the unique properties of each chronobiotic, thereby providing a robust and multifaceted resource for researchers and practitioners in the field.

PMID:40700252 | DOI:10.3390/clockssleep7030030

Biochem Soc Trans. 2025 Jul 22:BST20240469. doi: 10.1042/BST20240469. Online ahead of print.

ABSTRACT

Gastrulation is an essential process in the early embryonic development of all higher animals. During gastrulation, the three embryonic germ layers, the ectoderm, mesoderm and endoderm, form and move to their correct positions in the developing embryo. This process requires the integration of cell division, differentiation and movement of thousands of cells. These cell behaviours are coordinated through shortand long-range signalling and must involve feedback to execute gastrulation in a reproducible and robust manner. Mechanosensitive signalling pathways and processes are being uncovered, revealing that shortand long-range mechanical stresses integrate cell behaviours at the tissue and organism scale. Because the interactions between cell behaviours, signalling and feedback are complex, combining experimental and modelling approaches is necessary to elucidate the regulatory mechanisms that drive development. We highlight how recent experimental and theoretical studies provided key insights into mechanical feedback that coordinates relevant cell behaviours at the organism scale during gastrulation. We outline advances in modelling the mechanochemical processes controlling primitive streak formation in the early avian embryo and discuss future developments.

PMID:40700026 | DOI:10.1042/BST20240469