Bacterial exopolysaccharides mediate activation of flavin-containing monooxygenase 2 to extend lifespan in Caenorhabditis elegans

The gut microbiota plays a pivotal role in modulating host physiology and longevity through the production of microbial-derived molecules. Among these, bacterial exopolysaccharides (EPS) represent a structurally diverse group of surface polysaccharides with emerging roles in regulating host well-being. Here, we investigated the role of Lactobacillus strains with the capability to produce EPS, using Caenorhabditis elegans as a model organism. Results revealed significant lifespan extension in worms fed with EPS-producing bacteria, accompanied by improved health-span markers such as enhanced pharyngeal pumping and reduced lipofuscin accumulation. Transcriptomic profiling identified robust upregulation of the host detoxification and immune defense pathways, highlighting the flavin-containing monooxygenase gene fmo-2, as one of the major mediators of longevity and stress resistance triggered by EPS-producing lactobacilli. The effect was confirmed using fmo-2p::GFP reporter animals and was abrogated in fmo-2, hlh-30, and nhr-49 mutant backgrounds. Mechanistically, we demonstrated that EPS acts through a conserved transcriptional network that primarily relies on the activation of nhr-49/PPAR-α, with purified EPS being sufficient to activate fmo-2 expression. Our findings reveal that bacterial EPS activates host xenobiotic pathways to modulate aging, positioning it as a potential tool for microbiota-based longevity interventions. These insights show how microbial products can modulate fundamental biological processes across species, opening new strategies for age-related health interventions

Comparative RNA-Seq Analysis of Colon Spheroids and Patient-derived Tissues Identifies Non-Canonical Transcript Isoforms of Protein-Coding Genes Implicated in Colon Carcinogenesis

Objectives:This study aimed to identify transcript isoforms of protein-coding genes with potential relevance to the malignant transformation of gut mucosa.Methods:Colon cancer cell lines (HCT116, DLD1, SW620) and immortalized cells derived from healthy gut epithelium (HCEC-1CT) were cultured as spheroids and subjected to RNA sequencing to profile both canonical and non-canonical transcripts. The resulting data were compared with prior bioinformatics study findings that analyzed RNA-seq datasets from 473 patient-derived tumor and 417 non-tumor colon tissue samples.Results:Among 375 transcripts previously reported as significantly dysregulated in colon (39 up-regulated and 336 down-regulated), 32 transcripts displayed expression patterns in colon cell lines consistent with those observed in patient tissues (4 up-regulated and 28 down-regulated). In silico characterization of these molecules revealed that all of them exhibited at least 1 feature commonly associated with RNAs possessing regulatory functions, such as coding truncated protein isoform, exosomal localization, or enrichment in repetitive elements. The most prominently dysregulated transcripts with consistent expression profiles across both datasets were NTMT1-204 (up-regulated in cancer) and BLOC1S6-218 and DCTN1-205 (both down-regulated in cancer). The remaining 343 transcripts did not show consistent expression patterns in the cell lines, suggesting their dysregulation in patient-derived tissues may be due to the stromal or microenvironmental factors absent in vitro.Conclusion:In summary, this comparative transcriptomic analysis identified 32 transcript isoforms, comprising 2 canonical and 30 non-canonical transcripts, that may play regulatory roles in colon carcinogenesis and warrant further investigation in the context of gut epithelial cell biology

Multiphasic acute disseminated encephalomyelitis (MDEM) in a patient with systemic lupus erythematosus and C4A deficiency: case-based review

Acute disseminated encephalomyelitis (ADEM) is a fulminant inflammatory demyelinating disorder of the central nervous system, typically triggered by an aberrant immune response to infectious agents or vaccination. While ADEM is primarily observed in the pediatric population, it can also develop in adults; however, the precise host factors that increase susceptibility to ADEM remain poorly understood. Although ADEM has occasionally been reported in association with systemic lupus erythematosus (SLE), we present, to our knowledge, the first documented case of multiphasic ADEM in a patient with monogenic SLE caused by a homozygous frameshift mutation in the C4A gene. Herein, we provide a comprehensive literature review focusing on clinical manifestations and therapeutic approaches for ADEM and its multiphasic variants in SLE. Moreover, we propose a potential pathophysiological link between inherited C4A deficiency and susceptibility to central nervous system demyelination, offering novel insight into mechanisms underlying the development of ADEM in the context of SLE

Elucidating the enzymatic response of the white rot basidiomycete Abortiporus biennis for the downgrade of polystyrene

Plastic pollution is a growing global environmental concern, with polyolefins such as polyethylene and polypropylene, as well as polystyrene (PS) constituting a significant amount of plastic waste. Both polyolefins and PS, when inappropriately disposed of in the environment, contribute to environmental contamination since they degrade slowly, with both abiotic and biotic factors contributing to their downgrade. In terms of the microbial effect on plastics, in recent decades, several studies have focused on the biodeterioration and assimilation of polyolefins, while more comprehensive degradation of PS by diverse organisms, including bacteria, fungi, and even insect larvae, has been documented. The present study investigates the biocatalytic potential of the white-rot basidiomycete Abortiporus biennis LGAM 436 for PS degradation. Building on prior research, we examined the ability of this fungal strain to modify the structure of different PS forms, including commercial expanded polystyrene (EPS) foam and amorphous PS film. In addition, we explored the impact of olive oil mill wastewater (OOMW) effluent as an enzymatic inducer to enhance the degradation process. Through gel permeation chromatography (GPC), surface morphology changes, and FTIR-ATR analysis, we assessed the extent of PS degradation and identified relevant enzymatic activities via proteomics. The findings offer insights into the discovery of novel fungal biocatalysts for addressing plastic pollution, particularly through the action of high-redox oxidative enzymes

Significance of GSTM1 and GSTT1 Gene Deletions in Glioma Patients in Polish Population: Pilot Study

Background:Detoxification enzymes of the glutathione S-transferase (GST) family are cytosolic phase II detoxification enzymes and play an important role in the normal functioning of the human antioxidant system. When the normal function of GST is disturbed or absent, there can be disturbances in cell metabolism, proliferation, and apoptosis. Deletions in the GSTM1 and GSTT1 genes have been observed in several different diseases as well as in the development of cancer. There is a need to analyze the relationship between glioma and GSTM1 and GSTT1 gene deletion to better understand the relationship between brain tumors and GST polymorphisms, which is crucial for adopting a multidisciplinary approach to prognosis and treatment of brain tumors.Methods:In a cross-sectional clinical-laboratory study, gene deletions were examined in 34 patients with brain tumors originating from glial cells—gliomas and 88 healthy individuals. All participants were of Polish nationality and were not related.Results:An increase in GSTM1 and GSTT1 gene deletions was observed in glioma patients compared with the control group. The greatest increase showing a marked rise of 10 times (11.8% vs 1.14%, P < .05) is in the null genotype of both genes (GSTM1−/GSTT1) [odds ratio [OR] = 0.86; 95% confidence interval [CI] = 0.09-0.802] but less in the genotype with deletion of 1 GST gene (GSTM1−/GSTT1+ and GSTM1+/GSTT1−). In addition, the findings indicated a decrease in the non-deletion genotype of both genes (GSTM1+/GSTT1+) in healthy individuals. This study showed a higher frequency of GST gene deletion in glioma patients in the studied population.Conclusions:Based on the obtained findings, it can be said that the examination of the selected detoxification enzymes can be a useful marker in the diagnosis of glioblastoma

Functional Ambidexterity of an Ancient Nucleic Acid-Binding Domain

The helix-hairpin-helix (HhH) motif is an ancient and ubiquitous nucleic acid-binding element that has emerged as a model system for studying the evolution of dsDNA-binding domains from simple peptides that phase separate with RNA. We analyzed the entire putative evolutionary trajectory of the HhH motif – from a flexible peptide to a folded domain – for functional robustness to total chiral inversion. Against expectations, functional “ambidexterity” was observed for both the phase separation of HhH peptides with RNA and binding of the duplicated (HhH)2-Fold to dsDNA. Moreover, dissociation kinetics, mutational analysis, and molecular dynamics simulations revealed an overlap between the binding modes adopted by the natural and mirror-image proteins to natural dsDNA. The similarity of several dissociation phases upon chiral inversion may reflect the history of (HhH)2-Fold binding, with the ultimate emergence of a high-affinity binding mode, supported by a bridging metal ion, depopulating but not displacing more primitive (potentially ambidextrous) modes. These data underscore the surprising functional robustness of the HhH protein family and suggest that the veil between worlds with alternative chiral preferences may not be as impenetrable as is often assumed

Carotenoids in Paprika Fruits and Ajvar: Chemical Characterization and Biological Activity

In this study, carotenoids from four different paprika genotypes were analyzed at various maturation stages, as well as in Ajvar, a traditional Balkan product made from fully matured roasted paprika fruits. For this purpose, the HPTLC analytical method was used, and five dominant carotenoids were analyzed: β-carotene, lutein, zeaxanthin, capsanthin, and β-cryptoxanthin. Additionally, total carotenoids were analyzed spectrophotometrically, antioxidant capacity was determined, and their bioavailability was assayed using in vitro digestion. Finally, Raman spectroscopy, a non-destructive analytical method, was used to estimate the total carotenoid content. The results showed that the amount of all investigated carotenoids is the highest in the final maturity stage (0.38 g/100 g DM to 1.55 g/100 g DM). On the other hand, the lowest concentration of all investigated carotenoids was detected at the first stage of maturation, ranging from 0.01 g/100 g DM to 0.25 g/100 g DM. However, the analysis of carotenoid content in Ajvar showed a tendency for a decrease in concentration compared to their quantity in fresh fruits, although this was also dependent on the genotype (1.9–66.98% according to HPTLC results and 16.14–82.36% according to spectrophotometry). Antioxidant tests indicated an increase in antioxidant capacity with the ripening of paprika fruits, confirming the role of carotenoids as compounds capable of neutralizing harmful oxygen species (DPPH ranged from 0.21 to 1.50 µmol/g TEAC, CUPRAC ranged from 0.185 to 0.297 mg AsA/g DM, FRP ranged from 9.33 to 25.66 mg AsA/g DM). Quantification of total carotenoids by Raman spectroscopy showed that results were highly correlated with those obtained by HPTLC and the spectrophotometric method, highlighting the potential of Raman spectroscopy for carotenoid quantification. Based on the obtained results, it can be concluded that the traditional product Ajvar represents an important source of carotenoids, which are preserved after heat treatment with high biological activity relative to the final ripening stage of the paprika. Furthermore, the bioavailability of carotenoids from Ajvar is significantly higher compared to the results from fresh paprika analysis

High Expression Levels of the Long Non-Coding RNAs Lnc-IRF2-3 and Lnc-KIAA1755-4 Are Markers of Poor Prognosis in Chronic Lymphocytic Leukemia

Long non-coding RNAs (lncRNAs) play complex roles at multiple levels of gene regulation, thus modulating key cellular processes involved in the pathogenesis and progression of cancer. Aberrant expression of lncRNAs has been reported in various malignancies, including chronic lymphocytic leukemia (CLL). We investigated the expression of lnc-IRF2-3 and lnc-KIAA1755-4 in peripheral blood mononuclear cells of 112 previously untreated CLL patients by quantitative reverse-transcriptase polymerase chain reaction. Both lncRNAs were found to be overexpressed in CLL samples in comparison to healthy controls, and their high levels were associated with adverse clinico-biological characteristics of patients at diagnosis. High lnc-IRF2-3 expression was associated with high leukocyte and lymphocyte counts, high β2-microglobulin, advanced Binet stage, unfavorable cytogenetics, CD38-positivity and IGHV-unmutated status. Regarding lnc-KIAA1755-4, its high expression was associated with high leukocyte count, lymphocyte count, β2-microglobulin, lactate dehydrogenase and low hemoglobin, as well as with IGHV-unmutated status. In addition, we observed shorter time to first treatment and overall survival of patients expressing high levels of both lncRNAs in comparison to low-expressing patients. In summary, our study showed that high lnc-IRF2-3 and lnc-KIAA1755-4 expression at diagnosis predicts poor survival in CLL. The mechanisms of their upregulation, as well as their specific targets in CLL cells, remain to be elucidated

Biodegradable Electrospun PLGA Nanofibers-Encapsulated Trichinella Spiralis Antigens Protect from Relapsing Experimental Autoimmune Encephalomyelitis and Related Gut Microbiota Dysbiosis

Purpose: Trichinella spiralis has evolved complex immunomodulatory mechanisms mediated by excretory-secretory products (ESL1) that enable its survival in the host. Consequently, ESL1 antigens display excellent potential for treating autoimmune diseases such as multiple sclerosis (MS). However, whether timely controlled delivery of ESL1 antigens in vivo, as in natural infections, could enhance its therapeutic potential for MS is still unknown. Methods: To test this, we encapsulated ESL1 antigens into biodegradable poly (lactide-co-glycolic) acid (PLGA) nanofibers by emulsion electrospinning as a delivery system and assessed their release dynamics in vitro, and in an animal MS model, experimental autoimmune encephalomyelitis (EAE), induced 7 days after PLGA/ESL1 subcutaneous implantation. PLGA/ESL1 effects on EAE symptoms were monitored along with multiple immune cell subsets in target organs at the peak and recovery of EAE. Gut barrier function and microbiota composition were analyzed using qPCR, 16S rRNA sequencing, and metabolomic analyses. Results: ESL1 antigens, released from PLGA and drained via myeloid antigen-presenting cells through lymph nodes, protected the animals from developing EAE symptoms. These effects correlated with reduced activation of myeloid cells, increased IL-10 expression, and reduced accumulation of proinflammatory natural killer (NK) cells, T helper (Th)1 and Th17 cells in the spleen and central nervous system (CNS). Additionally, CD4+CD25hiFoxP3+ regulatory T cells and IL-10-producing B cells were expanded in PLGA/ESL1-treated animals, compared to control animals. The migration of ESL1 to the guts correlated with locally reduced inflammation and gut barrier damage. Additionally, PLGA/ESL1-treated animals displayed an unaltered microbiota characterized only by a more pronounced protective mevalonate pathway and expanded short-chain fatty acid-producing bacteria, which are known to suppress inflammation. Conclusion: The delivery of T. spiralis ESL1 antigens via biodegradable electrospun PLGA nanofiber implants efficiently protected the animals from developing EAE by inducing a beneficial immune response in the spleen, gut, and CNS. This platform provides excellent grounds for further development of novel MS therapies

Izmenjeni nivoi sfingolipidnih metabolita u serumu pacijenata sa lokalno uznapredovalim karcinomom rektuma: pilot studija

Background: Altered sphingolipid levels might contribute to rectal cancer development, progression and therapy response by regulating various biological processes, including apoptosis. This study aimed to analyse the serum sphingolipid profile in rectal cancer patients and investigate its association with the apoptotic status of tumour tissue and therapy response. Methods: Ceramide (CER) and sphingomyelin (SM) serum levels were analysed in 22 patients with locally advanced rectal cancer and 24 healthy individuals by ultrafast liquid chromatography coupled with tandem mass spectrometry. The expression of pro-apoptotic BAX (BCL2 associated X, apoptosis regulator) and anti-apoptotic BCL2 (BCL2 apoptosis regulator) was analysed in tumour and corresponding healthy tissue samples of patients by quantitative real-time PCR. Results: Significantly lower serum levels of C18 CER, C22 CER, C24 CER, C18 SM and C24 SM were observed in patients than in controls (P<0.05). For C20 CER, C22 CER and C24 CER, a positive correlation with the pro-apoptotic status of tumour tissue was found (r=0.619, P=0.018; r=0.694, P=0.006 and r=0.601, P=0.023, respectively). No difference in serum sphingolipid levels was found between patients with good, moderate, and poor responses to therapyUvod: Promene u nivou sfingolipida mogu da doprinesu nastanku karcinoma rektuma, progresiji bolesti i odgovoru na terapiju usled njihove regulacije razli~itih biolo{kih pro cesa uklju~uju}i apoptozu. Cilj ove studije je bio da se anali zira profil sfingolipida u serumu kod pacijenata sa karcinomom rektuma i da se ispita njegova povezanost sa apoptotskim statusom tkiva tumora i odgovorom na terapiju. Metode: Nivo ceramida (CER) i sfingomijelina (SM) je ana - liziran u serumu kod 22 pacijenta sa lokalno uznapredova - lim karcinomom rektuma i kod 24 zdrave osobe pomo}u ultrabrze te~ne hromatografije kombinovane sa tandem masenom spektrometrijom. Ekspresija pro-apoptotskog gena BAX (BCL2 asocirjau}i X, regulator apoptoze) i antiapoptotskog gena BCL2 (BCL2 regulator apoptoze) je ana - lizirana pomo}u metode kvantitativni PCR u realnom vremenu u uzorcima tumorskog tkiva i zdrave crevne sluznice kod pacijenata. Rezultati: Nivoi C18 CER, C22 CER, C24 CER, C18 SM i C24 SM su bili zna~ajno ni`i u serumu pacijenata u odnosu na kontrolnu grupu (P<0,05). Za C20 CER, C22 CER i C24 CER je utvr|ena pozitivna korelacija sa pro-apoptotskim statusom tumorskog tkiva (r=0,619, P=0,018; r=0,694, P=0,006 i r=0,601, P=0,023, respektivno). Nije prona|ena razlika u nivoima sfingolipida u serumu izme|u pacijenata sa dobrim, umerenim i lo{im odgovo - rom na terapiju