Metabolomics. 2025 Feb 7;21(1):24. doi: 10.1007/s11306-024-02220-0.

ABSTRACT

BACKGROUND: Chronic periodontitis is a condition impacting approximately 50% of the world's population. As chronic periodontitis progresses, the bacteria in the oral cavity change resulting in new microbial interactions which in turn influence metabolite production. Chronic periodontitis manifests with inflammation of the periodontal tissues, which is progressively developed due to bacterial infection and prolonged bacterial interaction with the host immune response. The bi-directional relationship between periodontitis and systemic diseases has been reported in many previous studies. Traditional diagnostic methods for chronic periodontitis and systemic diseases such as chronic kidney diseases (CKD) have limitations due to their invasiveness, requiring practised individuals for sample collection, frequent blood collection, and long waiting times for the results. More rapid methods are required to detect such systemic diseases, however, the metabolic profiles of the oral cavity first need to be determined.

AIM OF REVIEW: In this review, we explored metabolomics studies that have investigated salivary metabolic profiles associated with chronic periodontitis and systemic illnesses including CKD, oral cancer, Alzheimer's disease, Parkinsons's disease, and diabetes to highlight the most recent methodologies that have been applied in this field.

KEY SCIENTIFIC CONCEPTS OF THE REVIEW: Of the rapid, high throughput techniques for metabolite profiling, Nuclear magnetic resonance (NMR) spectroscopy was the most applied technique, followed by liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS). Furthermore, Raman spectroscopy was the most used vibrational spectroscopic technique for comparison of the saliva from periodontitis patients to healthy individuals, whilst Fourier Transform Infra-Red Spectroscopy (FT-IR) was not utilised as much in this field. A recommendation for cultivating periodontal bacteria in a synthetic medium designed to replicate the conditions and composition of saliva in the oral environment is suggested to facilitate the identification of their metabolites. This approach is instrumental in assessing the potential of these metabolites as biomarkers for systemic illnesses.

PMID:39920480 | DOI:10.1007/s11306-024-02220-0

Nat Immunol. 2025 Feb 7. doi: 10.1038/s41590-025-02099-6. Online ahead of print.

NO ABSTRACT

PMID:39920361 | DOI:10.1038/s41590-025-02099-6

Sci Rep. 2025 Feb 7;15(1):4627. doi: 10.1038/s41598-025-88168-0.

ABSTRACT

Essential oils (EO) are known for their antibacterial and anti-inflammatory properties and can be used as an alternative to reduce the reliance on antimicrobials in dairy cattle. While many studies have explored the beneficial properties of EO in vitro, their effects on milk quality and milk microbiota, when applied directly to the udder skin, remain relatively unknown. This study aimed to investigate the impact of Thymus capitatus essential oil (TCEO), known for its high antibacterial and antioxidant properties, on milk microbiota using 16S rRNA sequencing, the lipidomic profile via liquid chromatography-quadrupole time-of-flight mass spectrometry, udder skin microbiota, and inflammatory biomarkers of dairy cows at the end of lactation. Sixteen-quarters of 12 Holstein cows were selected, and TCEO was topically applied to the udder skin twice a day for 7 days. Milk was collected aseptically on days 0, 7, 21, and 28 before morning farm milking. The results showed no significant changes in microbiota composition after the EO treatment in alpha and beta diversity or taxonomical composition at the phylum and genus levels. TCEO induced limited changes in the milk lipidome, primarily affecting diacylglycerols at T21. The treatment did not affect inflammatory biomarkers, milk sensory properties, or quality. Our study is the first to demonstrate that a local application of 10% TCEO on cow's quarters does not significantly alter milk quality or microbiota composition in milk and skin. More studies should be conducted to ensure the safe use of TCEO in dairy cows and explore its potential benefits on antibiotic-resistant bacteria as an alternative or support for antibiotic therapy.

PMID:39920235 | DOI:10.1038/s41598-025-88168-0

Nat Commun. 2025 Feb 7;16(1):1452. doi: 10.1038/s41467-025-56425-5.

ABSTRACT

The history of clinical resistance to tetracycline antibiotics is characterized by cycles whereby the deployment of a new generation of drug molecules is quickly followed by the discovery of a new mechanism of resistance. This suggests mechanism-specific selection by each tetracycline generation; however, the evolutionary dynamics of this remain unclear. Here, we evaluate 24 recombinant Escherichia coli strains expressing tetracycline resistance genes from each mechanism (efflux pumps, ribosomal protection proteins, and enzymatic inactivation) in the context of each tetracycline generation. We employ a high-throughput barcode sequencing protocol that can discriminate between strains in mixed culture and quantify their relative abundances. We find that each mechanism is preferentially selected for by specific antibiotic generations, leading to their expansion. Remarkably, the minimum inhibitory concentration associated with individual genes is secondary to resistance mechanism for inter-mechanism relative fitness, but it does explain intra-mechanism relative fitness. These patterns match the history of clinical deployment of tetracycline drugs and resistance discovery in pathogens.

PMID:39920134 | DOI:10.1038/s41467-025-56425-5

Nat Commun. 2025 Feb 7;16(1):1460. doi: 10.1038/s41467-025-56603-5.

ABSTRACT

Type I Interferons (IFN-I) are central to host protection against viral infections, with plasmacytoid dendritic cells (pDC) being the most significant source, yet pDCs lose their IFN-I production capacity following an initial burst of IFN-I, resulting in susceptibility to secondary infections. The underlying mechanisms of these dynamics are not well understood. Here we find that viral infection reduces the capacity of pDCs to engage both oxidative and glycolytic metabolism. Mechanistically, we identify lactate dehydrogenase B (LDHB) as a positive regulator of pDC IFN-I production in mice and humans; meanwhile, LDHB deficiency is associated with suppressed IFN-I production, pDC metabolic capacity, and viral control following infection. In addition, preservation of LDHB expression is sufficient to partially retain the function of otherwise exhausted pDCs, both in vitro and in vivo. Furthermore, restoring LDHB in vivo in pDCs from infected mice increases IFNAR-dependent, infection-associated pathology. Our work thus identifies a mechanism for balancing immunity and pathology during viral infections, while also providing insight into the highly preserved infection-driven pDC inhibition.

PMID:39920132 | DOI:10.1038/s41467-025-56603-5

Stem Cell Reports. 2025 Jan 23:102398. doi: 10.1016/j.stemcr.2025.102398. Online ahead of print.

ABSTRACT

SOX17 directs the differentiation toward endoderm and acts as a human germline specifier. We previously found that the replacement of glutamate at position 57 of the high-mobility group (HMG) box with the basic lysine residue in SOX2 alters interactions with OCT4 and turns SOX17 into a pluripotency factor. Here, we systematically interrogated how mutations at this critical position affect the cellular reprogramming activity of SOX17 in mouse and human. We found that most mutations turn SOX17 into a pluripotency factor regardless of their biophysical properties except for acidic residues and proline. The conservative mutation to an aspartate allows the SOX17E57D protein to maintain a self-renewing endodermal state. We showed that only the glutamate in the wild-type protein blocks the formation of an SOX17/OCT4 dimer at composite DNA elements in pluripotency enhancers. Insights into how modifications of an ultra-conserved residue affect functions of developmental transcription factors provide avenues to advance cell fate engineering.

PMID:39919754 | DOI:10.1016/j.stemcr.2025.102398

Sci Total Environ. 2025 Feb 6;966:178713. doi: 10.1016/j.scitotenv.2025.178713. Online ahead of print.

ABSTRACT

In resource-limited producer-consumer systems, environmental variables such as weather, habitat structure, and resource availability interact to shape consumer dynamics. We conducted a comparative analysis on territorial Fremont's squirrel (Tamiasciurus fremonti) in Arizona mountain ranges (three sites) and non-territorial Eurasian red squirrel (Sciurus vulgaris) in the Italian Alps (five sites) to investigate the effects of forest composition, pulsed seed resources, weather, and climate change-induced forest disturbances on population density. We also explored potential synchrony in spatial and temporal dynamics between squirrel populations, driven by endogenous and exogenous processes. Our long-term, multi-site datasets revealed shared density-dependent patterns: annual oscillations in Fremont's squirrel populations and biennial oscillations in Eurasian red squirrels. Both species exhibited strong bottom-up responses, with higher densities following tree-seed production and warmer spring temperatures. Despite the absence of synchronized trends in population density across time or regions, we found consistent responses to resource availability and abiotic conditions, demonstrating shared mechanisms across ecologically distinct systems. By integrating field data, remotely sensed forest disturbances, and multi-factorial modeling, this study highlights the role of climate, forest dynamics, and climate change-induced forest disturbance in shaping population processes in pulsed resource systems. Our findings underscore the importance of understanding producer-consumer interactions under climate change, providing globally relevant insights into the interplay of abiotic drivers, species-specific behaviours, and ecological resilience. These results contribute to advancing strategies for wildlife conservation and forest management in the face of ongoing environmental change.

PMID:39919654 | DOI:10.1016/j.scitotenv.2025.178713

J Hazard Mater. 2025 Feb 3;488:137490. doi: 10.1016/j.jhazmat.2025.137490. Online ahead of print.

ABSTRACT

Mine waste disposal in dumps and stockpiles causes environmental pollution, particularly through microbe-assisted acid mine drainage (AMD) generation and groundwater contamination with hazardous heavy metal(loid)s. Metal hyper-resistance in acidophilic microorganisms remains an underexplored intriguing phenomenon. Using a multi-level approach, we provide the first data on extreme zinc resistance mechanisms in Sulfobacillus thermotolerans, recognized as one of the most metal-resistant organisms known. Under high zinc levels, Sb. thermotolerans cells exhibited efficient zinc sorption and low intracellular accumulation. Remarkably, mechanisms involved the upregulation of stress response and metabolic pathway proteins, including different GroEL chaperonin forms. Moreover, overexpression of the Sb. thermotolerans StGroEL chaperonin in Escherichia coli enhanced its growth and zinc resistance under zinc stress. 3D structure modeling and ion binding site prediction in StGroEL revealed 46 amino acid residues potentially involved in zinc docking. Thriving in natural and engineered environments, such as sulfide mines, mine waste disposal sites, and AMD, Sb. thermotolerans is a key member of acidophilic microbial communities used in commercial biotechnologies for sulfidic raw material processing. These findings, beyond their fundamental scientific relevance, have important implications for environmental protection, including AMD management, safe hazardous waste disposal, and a broader application of eco-friendly biomining technologies using metal-resistant microbial communities.

PMID:39919630 | DOI:10.1016/j.jhazmat.2025.137490

Drug Metab Dispos. 2024 Dec 12;53(2):100029. doi: 10.1016/j.dmd.2024.100029. Online ahead of print.

ABSTRACT

The liver contains multiple cell types, including resident cell types and immune cells. The liver is also categorized into 3 zones: periportal (zone 1), midzonal (zone 2), and centrilobular (zone 3). The goal of this study was to characterize the distribution of drug-processing genes (DPGs) in mouse liver using published single-cell and nuclei transcriptomic datasets, which were subjected to zonal deconvolution. Filtering, normalization, clustering, and differential expression analyses were performed using Seurat V5 in R. Hepatocytes were assigned to 3 zones based on known zonal markers and validated with published spatial transcriptomics data. Among the 195 DPGs profiled, most were expressed highest in hepatocytes (61.3%). Interestingly, certain DPGs were expressed most highly in nonparenchymal cells, such as in cholangiocytes (11.2%, eg, carboxylesterase [Ces] 2e, Ces2g), endothelial cells (7.2%, eg, aldo-keto reductase [Akr] 1c19, Akr1e1), Kupffer cells (5.3%, eg, Akr1a1, Akr1b10), stellate cells (5.1%, eg, retinoic acid receptor [Rar] α, Rarβ), myofibroblasts (2.9%, RAR-related orphan receptor [Rar] α), and a few were expressed in immune cell types. In hepatocytes, 72.4% of phase-I enzymes were enriched in zone 3. Phase-II conjugation enzymes such as UDP-glucuronosyltransferases (75%) were enriched in zone 3, whereas sulfotransferases (40%) were enriched in zone 1. Hepatic xenobiotic transporters were enriched in zone 3. The xenobiotic biotransformation-regulating transcription factors were enriched in zone 3 hepatocytes. The enrichment of DPGs in liver cell types, including non-parenchymal cells and zone 1 hepatocytes, may serve as an additional repertoire for xenobiotic biotransformation. SIGNIFICANCE STATEMENT: Our study is among the first to systematically characterize the baseline mRNA enrichment of important drug-processing genes in different cell types and zones in the liver. This finding will aid in further understanding the mechanisms of chemical-induced liver injury with improved resolution and precision.

PMID:39919554 | DOI:10.1016/j.dmd.2024.100029

Int Immunopharmacol. 2025 Feb 6;149:114204. doi: 10.1016/j.intimp.2025.114204. Online ahead of print.

ABSTRACT

BACKGROUND: Alkylating cellular DNA, sulfur mustard (SM) is a chemical warfare agent that causes severe damage to the skin, eyes, and respiratory tract. Exposure can result in painful burns, chronic lung disease, immune system suppression, and an increased chance of developing cancer. The symptoms of itching, redness, and blistering are frequently followed by long-term genetic and psychological damage. By exploring the interaction between microRNA (miRNA), mRNA, and long non-coding RNA (lncRNA) in these patients, it is possible to identify gene expression patterns that could reduce cancer risk or improve treatment outcomes.

METHODS: The purpose of this study is to examine transcriptome data from PBMC samples obtained from sulfur mustard exposed patients (Mild, Moderate, Severe) and healthy Control, separated into six groups (SC, SMo, SMi, MoMi, MoC, and MiC). miRNA, lncRNA, and mRNA interactions were explored using miRNA, lncRNA, and mRNA tools and databases, such as miRTarBase, miRDB, miRNET, miRcode, and DIANA. A tripartite mRNA-miRNA-lncRNA network was modeled with the aid of Cytoscape software, and functional analyses were performed to gain an understanding of molecular pathways using GO and KEGG functional analyses.

RESULTS: By extracting miRNAs shared between lncRNAs and mRNAs, six groups were identified and Cytoscape software was used to visualize the lncRNA-miRNA-mRNA network. Betweenness, closeness, and degree filters identified key genes, with INO80D and lncRNAs MINCR, LINC00662, NEAT1, and DHRS4-AS1, along with miRNAs hsa-miR-1-3p, hsa-miR-124-3p, and hsa-let-7b-5p as the main players in all groups.

CONCLUSION: The interaction between key genes involved in chemical injuries and their association with genes implicated in lung cancer is highlighted in this study. By targeting these genes and their proteins, we can improve treatment strategies for sulfur mustard exposed patients and potentially reduce lung cancer risk.

PMID:39919453 | DOI:10.1016/j.intimp.2025.114204

Sci Immunol. 2025 Feb 7;10(104):eadp6667. doi: 10.1126/sciimmunol.adp6667. Epub 2025 Feb 7.

ABSTRACT

The bone marrow microenvironment plays a crucial role in the development of multiple myeloma. As the disease progresses, malignant myeloma cells can evolve to survive outside the bone marrow. However, the processes underlying bone marrow independence and their consequences for immune control remain poorly understood. Here, we conducted single-cell and spatial multiomics analyses of bone marrow-confined intramedullary disease and paired breakout lesions that disrupt the cortical bone. These analyses revealed a distinct cellular microenvironment and architectural features of breakout lesions, characterized by extensive areas of malignant plasma cells interspersed with lesion-specific solitary natural killer and macrophage populations, as well as focal accumulations of immune cell agglomerates. Within these agglomerates, spatially confined T cell clones expanded alongside various immune cells, coinciding with the local genomic evolution of tumor cells. These analyses identify breakout lesions as a hotspot for tumor-immune cell interactions and diversification, representing a key event in myeloma pathogenesis.

PMID:39919199 | DOI:10.1126/sciimmunol.adp6667

PLoS One. 2025 Feb 7;20(2):e0316368. doi: 10.1371/journal.pone.0316368. eCollection 2025.

ABSTRACT

The COVID-19 (SARS-CoV-2) pandemic has led to a significant mortality globally and persistent health challenges in many survivors. Early accurate diagnosis, surveillance, identification of cohorts, and prophylaxis are considered essential measures to reduce the spread of infectious viral pathogens such as SARS-CoV-2. A reliable, fast, high-throughput screening method that can detect viral particles and identify the pathogenic virus in infected individuals could help to reduce the spread of the next viral threat through quick knowledge and implementation of appropriate prevention strategies. Since respiratory viruses are typically present in nasal and oral secretions, saliva is a good target for testing for viral infections. Saliva testing has slowly gained popularity in the diagnostics based on biomarkers and other constituents ranging from organic compounds (e.g., food additives), peptides, and even microorganisms. Polymerase chain reaction (PCR) remains the gold standard for sensitive detection of SARS-CoV-2 infection in biological samples. However, while PCR testing for COVID is sensitive and widely used by hospitals, the method has a false-negative rate of 15-20% and is kit-based necessitating the development of alternative methods of detection that provide higher accuracy. This paper describes the use of a SpecID Mass Spectrometer that can detect the presence of viral particles in saliva at very low levels (<500 virions/0.5 ml). The main goal of this study was to demonstrate that our previously developed, portable, mass spectrometry based method, SpecID, could also be sued for detecting viruses in saliva, including but not limited to SARS-CoV-2; the SpecID method has the potential to provide a reliable solution that overcomes some of the challenges with molecular testing like PCR.

PMID:39919111 | DOI:10.1371/journal.pone.0316368

PLoS One. 2025 Feb 7;20(2):e0317672. doi: 10.1371/journal.pone.0317672. eCollection 2025.

ABSTRACT

Extreme temperatures associated with climate change are expected to impact the physiology and fertility of a variety of insects, including honey bees. Most previous work on this topic has focused on female honey bees (workers and queens), and comparatively little research has investigated how heat exposure affects males (drones). To address this gap, we tested body mass, viral infections, and population origin as predictors of drone survival and sperm viability in a series of heat challenge assays. We found that individual body mass was highly influential, with heavier drones being more likely to survive a heat challenge (4 h at 42°C) than smaller drones. In a separate experiment, we compared the survival of Northern California and Southern California drones in response to the same heat challenge (4 h at 42°C), and found that Southern Californian drones - which are enriched for African ancestry - were more likely to survive a heat challenge than drones originating from Northern California. To avoid survivor bias, we conducted sperm heat challenges using in vitro assays and found remarkable variation in sperm heat resilience among drones sourced from different commercial beekeeping operations, with some exhibiting no reduction in sperm viability after heat challenge and others exhibiting a 75% reduction in sperm viability. Further investigating potential causal factors for such variation, we found no association between drone mass and viability of sperm in in vitro sperm heat challenge assays, but virus inoculation (with Israeli acute paralysis virus) exacerbated the negative effect of heat on sperm viability. These experiments establish a vital framework for understanding the importance of population origin and comorbidities for drone heat sensitivity.

PMID:39919074 | DOI:10.1371/journal.pone.0317672

ALTEX. 2025 Jan 20. doi: 10.14573/altex.2412241. Online ahead of print.

ABSTRACT

Chemical safety assessment still heavily relies on animal testing, presenting ethical dilemmas and limited human predictive value. New approach methodologies (NAMs), including in vitro and in silico techniques, offer alternative solutions. In silico toxicology has made progress in predicting chemical effects but frequently lacks biological mechanistic foundations. Recent developments focus on mechanistic understanding of adverse effects inflicted by chemicals, as embedded in (quantitative) adverse outcome pathways (AOPs). However, there is a demand for more detailed mechanistic insights at the gene and cell levels, encompassing both pathology and physiology. Drawing inspiration from the Disease Maps Project, this paper introduces Physiological Maps (PMs) as comprehensive graphical representations of biochemical processes related to specific organ functions. PMs are standardized using Systems Biology Graphical Notation and controlled vocabularies and annotations. Curation guidelines have been developed to ensure reproducibility and usability. This paper presents the methodology used to build PMs, emphasizing the essential collaboration between domain experts and curators. PMs offer user-friendly, standardized visualization for data analysis and educational purposes. Enabling a better understanding of (patho)physiology, they also complement and support the development of AOPs by providing detailed mechanistic information at the gene and cell level. Furthermore, PMs contribute to developing in vitro test batteries and to building (dynamic) in silico models aiming to predict the toxicity of chemicals. Collaborative efforts between the toxicology and systems biology communities are crucial for creating standardized and comprehensive PMs, supporting and accelerating the development of human-relevant NAMs for next-generation risk assessment.

PMID:39918919 | DOI:10.14573/altex.2412241

J Phys Chem B. 2025 Feb 7. doi: 10.1021/acs.jpcb.4c08267. Online ahead of print.

ABSTRACT

We report a computational protocol for simulating electric field gradient dynamics around Na+ cations in mixtures of 1-ethyl-3-methylimidazolium tetrafluoroborate ([Im21][BF4]) and water validated by comparison to measurements of nuclear magnetic resonance (NMR) T1 relaxation times. Our protocol combines classical molecular dynamics simulations of a scaled charge model of [Im21][BF4] and TIP4Pew water to generate the electric field gradient (EFG) correlation function, CEFG(t), with quantum chemical calculations for determining the EFG variance ⟨Vzz2⟩. Although we demonstrate that the Sternheimer approximation is as valid in these mixtures as it is in neat water, we do not recommend using the Sternheimer approximation as it underestimates ⟨Vzz2⟩ by ∼10% compared to a set of computationally efficient density functional theory calculations. Our protocol is capable of reproducing both the composition- and temperature-dependence of T1 over the full range of experimentally accessible [Im21][BF4]/water compositions and a temperature range of 285-350 K. We also show that scaling the [Im21][BF4] charges does not simply speed up the dynamics of the solvent, but has effects on the shape of CEFG(t). Following validation of our protocol, we analyze the shape and relaxation times of CEFG(t) to show that the mechanism by with T1 changes is different when the composition of the mixture varies compared to changes in temperature. As composition changes, the balance between inertial and diffusive relaxation alters, whereas temperature only affects the time scale of the diffusion portion of the relaxation. We also show that solvation shell of Na+ in these mixtures is significantly more labile than in neat [Im21][BF4] and that water and BF4- anions compete to be in the Na+ solvation shell. This validated computational protocol opens the door to more detailed interpretation of NMR T1 relaxation experiments of monatomic ions in complex liquid environments.

PMID:39918115 | DOI:10.1021/acs.jpcb.4c08267

J Clin Endocrinol Metab. 2025 Feb 7:dgaf073. doi: 10.1210/clinem/dgaf073. Online ahead of print.

ABSTRACT

OBJECTIVE: Fetuin B is a steatosis-responsive hepatokine that induces glucose intolerance in mice. Recently, we found that fetuin B in white adipose tissue was positively associated with peripheral insulin resistance in mice and a small study population, possibly through a fetuin B-induced inflammatory response in adipocytes. This translational study aimed to investigate the link between plasma fetuin B and the adipose tissue transcriptome and plasma proteome in a large cohort of humans.

METHODS: Continuous linear regression analysis in R was applied to investigate the link between plasma fetuin B and the adipose tissue transcriptome (n=207) and plasma proteome (n=558) in humans, after adjustment for sex, age and study centre (model 1), model 1 + BMI (model 2) and model 2 + insulin sensitivity (MATSUDA-index) (model 3).

RESULTS: Plasma fetuin B was associated with >100 genes in white adipose tissue, belonging to pathways related to cytokine/chemokine signaling (models 1 and 2) and insulin signaling (all models), and with >146 plasma proteins, involved in pathways related to metabolic processes and insulin signaling (all models).

CONCLUSION: Plasma fetuin B is related to adipose tissue genes and plasma proteins involved in metabolic processes and insulin signaling. Our findings provide evidence for the involvement of white adipose tissue in fetuin B-induced insulin resistance.

PMID:39918061 | DOI:10.1210/clinem/dgaf073

J Physiol Investig. 2025 Feb 7. doi: 10.4103/ejpi.EJPI-D-24-00090. Online ahead of print.

ABSTRACT

Inflammatory bowel disease (IBD) is an autoimmune disorder characterized by chronic inflammation of the gut and compromised intestinal barrier function, resulting from aberrant immune responses targeting the intestinal microbiota. While the involvement of Candida albicans in IBD pathogenesis is well-documented, the role of non-albicans Candida species in IBD remains less understood. Recent studies have identified a correlation between elevated levels of Candida tropicalis, a notable non-albicans opportunistic fungus, and the development of IBD. However, the precise impact of C. tropicalis on intestinal barrier function is not well elucidated. To address this knowledge gap, we utilized a cell model comprising polarized Caco-2 monolayers, which mimic the intestinal epithelium, to investigate the interaction between C. tropicalis and intestinal barrier function. Our results showed that incubation with C. tropicalis influenced transepithelial electrical resistance and increased permeability to the small molecule lucifer yellow, but did not affect permeability to the larger molecule fluorescein isothiocyanate-dextran. In addition, we observed internalization of the tight junction protein claudin-1 in the Caco-2 monolayers. Further experiments using Caco-2 monolayers exposed to the dectin-1 ligand zymosan induced similar changes in the distribution of claudin-1 but did not alter monolayer permeability. These findings suggest that C. tropicalis specifically affects intestinal barrier integrity and permeability to smaller solutes in intestinal epithelial cells.

PMID:39918057 | DOI:10.4103/ejpi.EJPI-D-24-00090

Comb Chem High Throughput Screen. 2025 Feb 4. doi: 10.2174/0113862073335295241216152011. Online ahead of print.

ABSTRACT

AIMS: The primary objective of this study is to explore the impact of Ganfule (GFL), a traditional Chinese medicine, on differentially expressed genes (DEGs) linked to nonalcoholic fatty liver disease (NAFLD). By identifying potential biomarkers, we seek to enhance GFL's clinical efficacy through targeted pharmaceutical design.

BACKGROUND: NAFLD a prevalent liver disorder, is often associated with obesity and metabolic syndrome. While GFL has demonstrated clinical efficacy in treating NAFLD, its precise targets and mechanisms of action remain elusive. Understanding these mechanisms could pave the way for more effective treatments.

OBJECTIVES: GFL, a long-standing traditional Chinese medicine (TCM), has demonstrated clinical effectiveness in treating NAFLD. However, its precise targets and mechanism of action remain elusive. In this study, we aim to explore GFL's impact on differentially expressed genes, which could potentially serve as biomarkers for developing targeted therapies. This approach is intended to enhance GFL's clinical efficacy by identifying key genes that respond to its treatment.

METHODS: To induce NAFLD, 23 Sprague-Dawley rats were fed a high-fat diet. These rats were then categorized into three groups: normal diet (NOR), high-fat diet model (HFD), and those treated with GFL. Highthroughput sequencing was employed to identify DEGs in their livers. Utilizing the STRING and DAVID databases, we analyzed potential protein interactions expressed by these genes. Furthermore, the KEGG, Reactome, and Wiki databases aided in determining their biological roles and signaling pathways. Key DEGs' mRNA expression levels and corresponding proteins were further screened and confirmed through haematoxylin- eosin staining (HE), immunohistochemistry (IHC), Real-Time Quantitative Reverse Transcription Polymerase Chain Reaction (RT-qPCR), and western blotting.

RESULTS: Significant variations in DEGs were observed across the three groups, with 19 intersecting genes identified within a cluster of 90 NAFLD-related genes. GFL was found to adjust the expression of nine core DEGs, including Abcg1, Igfgb1, Lepr, Pdk4, Socs3, and Stat3. These genes-related proteins are tied to proteins such as FABP4, LEPR, SCD1, SOCS3, and STAT3, which are intimately connected to adipocytokine and adipogenesis pathways. Our study reveals that GFL modifies the expression of IGFBP1, LEPR, PDK4, SCD1, and SOCS3, thereby regulating the adipocytokine, JAK-STAT, leptin-insulin signaling, and adipogenesis metabolic pathways, respectively.

CONCLUSIONS: This study enhances understanding of GFL's efficacy and identifies potential biomarkers for NAFLD treatment. Optimizing GFL's efficacy and elucidating its mechanism provides a methodological reference for traditional Chinese medicine exploration.

PMID:39917919 | DOI:10.2174/0113862073335295241216152011

Front Dent Med. 2024 May 16;5:1374883. doi: 10.3389/fdmed.2024.1374883. eCollection 2024.

ABSTRACT

This Special Issue was initiated in response to the call for improved research by the National Academies of Sciences, Engineering, and Medicine (NASEM) (United States) Consensus Study Report on Temporomandibular Disorders (TMDs), a set of putatively localized musculoskeletal conditions. In this Special Issue, the importance of systems biology for TMDs emerges from each of three separate publications. The importance of systems biology to patients is anchored in two domains-laboratory research and clinical observation. The three publications fully speak to the underlying goals in the NASEM recommendations for initiatives: that research on TMDs needs to broaden, that integration between basic and clinical science needs to improve, and that while better evidence is needed, clinicians need to utilize the evidence that already exists. All three of these initiatives, taken together, would lead to better understanding of these complex diseases and to better care of patients with these diseases.

PMID:39917712 | PMC:PMC11797808 | DOI:10.3389/fdmed.2024.1374883

F1000Res. 2024 Dec 24;13:1559. doi: 10.12688/f1000research.160226.1. eCollection 2024.

ABSTRACT

VAPB is an adaptor protein known for its role as an anchor for other proteins at the endoplasmic reticulum. A mutant form of VAPB has been linked to amyotrophic lateral sclerosis and the underlying mechanisms resulting from this defect are studied by researchers in this area to uncover its implication in the disease. Here we have characterized six VAPB commercial antibodies for western blot, immunoprecipitation, and immunofluorescence using a standardized experimental protocol based on comparing read-outs in knockout cell lines and isogenic parental controls. These studies are part of a larger, collaborative initiative seeking to address antibody reproducibility issues by characterizing commercially available antibodies for human proteins and publishing the results openly as a resource for the scientific community. While use of antibodies and protocols vary between laboratories, we encourage readers to use this report as a guide to select the most appropriate antibodies for their specific needs.

PMID:39916983 | PMC:PMC11799760 | DOI:10.12688/f1000research.160226.1