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Silicon alleviates copper toxicity: Insights from transcriptome and miRNAome analysis
No full textCopper (Cu) is an essential micronutrient for plants that plays a crucial role in photosynthesis,
respiration and oxidative stress defense. However, excessive accumulation of Cu is toxic and leads to
oxidative damage, growth inhibition and disruption of the nutrient balance. Silicon (Si) has been
reported to enhance the tolerance of plants to various abiotic stress factors, including the toxicity of
heavy metals. Despite accumulating evidence of Si’s protective role, the molecular mechanisms
underlying its mitigation of Cu toxicity remain largely unexplored. In this study, we investigated the
effects of Si supplementation on cucumber plants exposed to Cu excess using a comprehensive omics
approach combining transcriptome (RNA-seq) and miRNAome profiling (small RNA-seq). Cucumber
roots exposed to Cu stress (± Si) were analyzed to elucidate changes in gene expression and regulatory
miRNA networks involved in stress response and tolerance. Transcriptome analysis revealed 7,114
differentially expressed genes (DEGs) in the Cu-treated plants and 5,375 DEGs in the Cu+Si treated
plants compared to the control. In particular, 2,462 DEGs were identified when the Cu+Si treatment
was compared to the Cu treatment alone. Gene Ontology (GO) enrichment analysis showed that Si
affected genes involved in redox homeostasis and membrane stabilization under Cu stress. The most
enriched GO term was “transmembrane transporter activity” with a greater number of upregulated than
downregulated genes. Si modulated the expression of key genes involved in Cu homeostasis and
detoxification, including Cu-transporters, Cu-binding proteins and antioxidative defense enzymes. In
parallel, small RNA profiling identified 25 differentially expressed miRNAs (16 known and 9 novel)
upon Cu+Si treatment compared to Cu treatment. Among them were Cu-responsive miRNAs such as
miR398 and miR408, which were significantly downregulated by Si supplementation. These miRNAs
are known regulators of genes encoding Cu-binding proteins, suggesting that Si affects Cu stress
tolerance via post-transcriptional regulation. Together, these findings demonstrate that Si mitigates Cu
toxicity through coordinated transcriptional and post-transcriptional reprogramming. The integrative
omics approach provides new insights into the complex molecular mechanisms by which Si enhances
metal tolerance, offering potential targets for improving stress resilience in plants.Book of abstract: 9th International Conference on Silicon in Agriculture (ICSA 2025), September 15–19, 2025 in Belgrade
Oral administration of the probiotic strain Lactobacillus helveticus BGRA43 reduces high-fat diet–induced hepatic steatosis in mice and restores gut microbiota composition
No full textIntroductionThe prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is rapidly increasing. Modulation of the gut microbiota through the use of probiotics has been recognized as an important option for the treatment of hepatic steatosis. Previous studies suggested that the bacterial strain Lactobacillus helveticus BGRA43 (LHBGRA43) can reduce inflammation and improve the bacterial balance in the gut. The aim of this study was to investigate whether oral administration of LHBGRA43 in mice fed a high-fat diet contributes to the reduction of hepatic steatosis through its beneficial effects on the composition of the gut microbiota.MethodsMale C57BL/6J mice (2.5 months old) were divided into three groups: a control group fed a standard diet (10% kcal fat), a high-fat diet (HFD) group (60% kcal fat for 14 weeks) and a HFD group that received freeze-dried LHBGRA43 dissolved in PBS orally for the last 5 weeks of the diet.ResultsHistological analysis of the liver showed that animals fed HFD exhibited hepatic steatosis, while no lipid droplets were present in the liver of animals receiving LHBGRA43. This decrease in steatosis correlated with decreased level of sterol regulatory element-binding protein-1c, reduced expression of the fatty acid transporter Cd36, enzymes involved in ceramide synthesis and proinflammatory markers. The administration of LHBGRA43 also improved the integrity of the small intestine barrier, as evidenced by an increased level of ZO-1 protein. The observed reduction in intestinal permeability was associated with a decreased Firmicutes/Bacteroidota ratio and increased abundance of the genera Alistipes, Acetatifactor and Odoribacter, as well as a decreased concentration of branched-chain 4-methylvaleric acids.DiscussionIn conclusion, the restoration of the gut microbiota composition in combination with the strengthening of the small intestine barrier suggests that LHBGRA43 could be used as a general probiotic strain with ameliorative effects on hepatic lipid accumulation and lipotoxicity.The Supplementary Material for this article can be found online at:[https://www.frontiersin.org/articles/10.3389/fphar.2025.1688777/ full#supplementary-material
The K77 capsular polysaccharides as determinants of virulence and resistance in hypermucoid clinical isolate Acinetobacter baumannii 10593
No full textAcinetobacter baumannii is an opportunistic pathogen and a major cause of hospital-acquired
infections worldwide, with intrinsic antibiotic resistance and remarkable desiccation tolerance.
Important virulence factor is the polysaccharide capsule which protects the bacteria from
environmental stressors, including antimicrobials and the host immune response. With limited
treatment options, capsular polysaccharides have become promising vaccine targets. To investigate
the biological role and function of the capsule, the clinical isolate A. baumannii 10593,
characterized by a hypermucoid phenotype, was selected from the laboratory’s collection. The
capsule biosynthesis genes are clustered in the K locus. Following whole genome sequencing of
the selected isolate, the KAPTIVE tool was used to analyse the K locus type, which was identified
as KL77. Subsequently, the galU gene, involved in the biosynthesis of simple sugars, was selected
for mutagenesis, and a corresponding knockout strain was successfully generated. The outcome of
the selected gene deletion was assessed by comparing biofilm production between the wild type
and the mutant strain using fluorescence microscopy, with the mutant showing a higher ability to
form biofilm. The constructed deletion mutant was further employed to investigate the role of the
capsule in several key aspects of A. baumannii pathogenicity, including antimicrobial resistance
and tolerance to disinfectants. The knockout strain showed increased susceptibility to all tested
disinfectants (benzalkonium chloride, benzethonium chloride, and chlorhexidine digluconate) and
most antibiotics used in this study (meropenem, ciprofloxacin, gentamicin, amikacin, tobramycin,
and colistin). Adhesion to extracellular matrix proteins (collagen type I and fibronectin) was
examined and it was demonstrated that the mutant was able to adhere more strongly to these
proteins compared to the wild type. Furthermore, LDH cytotoxicity assay using human
keratinocyte line (HaCaT) showed that the mutant strain was less cytotoxic and therefore less
virulent towards host cells than the wild type strain. Based on these findings, the K77 capsular
polysaccharides play a significant role in the pathogenicity of A. baumannii 10593, as they enhance
resistance to antimicrobials and disinfectants as well as cytotoxicity, whereas their disruption
promotes bacterial adhesion.Book of abstract:6 BALKAN
CONFERENCE ON
BIOSCIENCES 30-31 OCT 2025
PLOVDIV, BULGARI
Prognostic significance of the long non-coding RNAs lnc-IRF2-3 and lnc-KIAA1755-4 in chronic lymphocytic leukemia
No full textAberrant expression of long non-coding RNAs (lncRNAs) has been reported in many cancers,
including B-cell malignancies. By modulating the expression of various genes, lncRNAs are
involved in the pathogenesis, disease progression and treatment outcome. The aim of this study
was to analyze the expression patterns of lnc-IRF2-3 and lnc-KIAA1755-4 in chronic lymphocytic
leukemia (CLL), and to evaluate their association with clinico-biological characteristics of patients
(pts) at diagnosis and survival. The expression of the investigated lncRNAs was measured in
peripheral blood mononuclear cells of 112 previously untreated CLL pts by qRT-PCR; median
expression levels were used as a cut-off to discriminate between high- and low-expressing cases.
High lnc-IRF2-3 levels were associated with high leukocyte and lymphocyte counts, high β2-
microglobulin, advanced Binet stage, unfavorable cytogenetics, CD38-positivity and IGHVunmutated
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. Expression of both lncRNAs was higher in pts with
intermediate, high and very high CLL-IPI scores in comparison to pts with low CLL-IPI before the
initiation of treatment. In addition, we observed shorter time to first treatment (TTFT) and overall
survival (OS) of pts expressing high levels of lnc-IRF2-3 in comparison to low-expressing pts. The
same association with shorter TTFT and OS was found regarding high expression of lnc-
KIAA1755-4. Moreover, the shortest TTFT and OS were detected in pts with concomitant high
expression of both lncRNAs. In conclusion, our results show that elevated expression of lnc-IRF2-
3 and lnc-KIAA1755-4 at diagnosis predicts adverse prognosis in CLL. The causes of their
upregulation, as well as their mechanisms of action in CLL cells remain to be elucidated.Book of abstract:6 BALKAN CONFERENCE ON BIOSCIENCES 30-31 OCT 2025 PLOVDIV, BULGARI
Uporedna analiza bioloških aktivnosti divljih i kultivisanih biljaka vrste Helichrysum italicum
No full textVrsta Helichrysum italicum (Roth) G. Don (Compositae), smilje, visoko je cijenjena biljka u
tradicionalnoj medicini Balkana, gdje se koristi u obliku čajeva, tinktura i melema za liječenje
kožnih oboljenja, rana, respiratornih i probavnih tegoba, te upala. Cilj ovog istraživanja bio je
uporedno ispitivanje antioksidativnih, antidijabetičkih i antiinflamatornih svojstava lista i
nadzemnog dijela u fazi cvijetanja divljih i kultivisanih biljaka vrste H. italicum, kao i
određivanje koncentracije ukupnih fenolnih jedinjenja. Antioksidativna aktivnost etanolnih
ekstrakata određena je spektrofotometrijskim metodama zasnovanim na sposobnosti doniranja
elektrona i redukciji metala, antidijabetička kao sposobnost inhibicije aktivnosti α-amilaze i α-
glukozidaze, a antiinflamatorna kao sposobnost inhibicije denaturacije proteina. Etanolni
ekstrakti divljih biljaka vrste H. italicum sadržavali su znatno veću koncentraciju fenolnih
jedinjenja u listu (746 ± 9 mg/gDW) i nadzemnom dijelu (513 ± 8 mg/gDW) u odnosu na
kultivisane biljke. Uzorci divljih biljaka pokazali su veći ukupni antioksidativni kapacitet, kao
i izraženiju antidijabetičku i antiinflamatornu aktivnost, dok je sposobnost redukcije prelaznih
metala bila slična kod obje grupe. Intenzivnija sinteza fenolnih jedinjenja kod H. italicum iz
prirodnih staništa doprinosi jačoj biološkoj aktivnosti te ukazuje na moguću primjenu u
fitoterapiji.Zbornik sažetaka: V simpozijum biologa i ekologa Republike Srpske sa međunarodnim učešćem - SBERS 2025 Prirodnomatematički fakultet, Univerzitet u Banjoj Luci, 13-15. novembar 202
Editorial: Probiotics for global health: advances, applications and challenges
No full textIn recent decades, probiotics have become a central focus in biomedical and nutritional sciences due to their ability to support host health, prevent disease, and counteract dysbiosis. Given the rising global burden of diseases, there is an urgent need for safe, sustainable, and accessible interventions to complement conventional therapies. Probiotics, defined as live microorganisms that confer a health benefit when administered in adequate amounts, represent a promising strategy to improve public health across diverse populations and life stages. This Research Topic was conceived to examine the role of probiotics in advancing global health and contributing to the United Nations Sustainable Development Goal 3 (SDG3): "Ensure healthy lives and promote well-being for all at all ages." The contributions published here highlight the multifaceted impact of probiotics on human well-being, spanning infectious disease prevention, management of chronic conditions, maternal and infant health, mental health, and the mitigation of antimicrobial resistance.A consistent theme is the ability of probiotics to reduce pathogen colonization, enhance mucosal defenses, and modulate immune responses, offering cost-effective approaches to alleviating infectious disease in vulnerable populations. Probiotics also help manage non-communicable diseases like cancer, cardiovascular disorders, diabetes, and obesity by modulating metabolism, reducing inflammation, and strengthening the gut barrier. Probiotic interventions further support maternal health and infant development, while early-life supplementation can reduce the risk of neonatal infections, allergies, and gastrointestinal disorders.Probiotics are increasingly studied in the gut-brain axis, with evidence of their impact on neurotransmitters, neuroinflammation, and stress. Finally, their contribution to combating antimicrobial resistance (AR) emphasizes their global relevance for both medicine and agriculture.Taken together, this Research Topic synthesizes recent advances, highlighting both opportunities and challenges of probiotic science, and underscores their potential to transform preventive health strategies and therapeutic interventions in line with global health priorities.Current Research Topic brought together 31 unique contributions, collectively illustrating the breadth and diversification of probiotic research (Table 1). A clear taxonomic pattern emerges, reflecting both the maturity of classical probiotic investigations and the growing interest in non-traditional microbial candidates.The Lactobacillus lineage, including Lacticaseibacillus, Limosilactobacillus, and Lactiplantibacillus species, was by far the most represented group. Twelve studies, presented, for example, by Wang et al.; Kiousi et al.; Dong et al., Zhang et al., account for almost 39% of the collected works. Their predominance reflects long-standing GRAS status of lactobacilli, resilience in gastrointestinal environments, immunomodulatory mechanisms, and wide availability in food and pharmaceutical markets.By contrast, only two articles specifically addressed the genus Bifidobacterium (Ma et al., 2024;Sarita et al., 2024), one of which is a general review covering multiple probiotics (Sarita et al., 2024). Despite the genus' central role in early-life microbiota, immune development, and pediatric health, this limited representation underscores both a gap and an opportunity for further exploration of bifidobacterial strains in clinical and nutritional contexts.Another single study was dedicated to Bacillus spore-formers, specifically Bacillus coagulans (Kallur et al., 2024). With its exceptional resistance to heat, acidity, and processing stress, B. coagulans is gaining recognition as a robust probiotic candidate for scalable food and nutraceutical applications.In addition, next-generation probiotics received initial but promising attention. An article examined Akkermansia muciniphila (Lu et al., 2024), reflecting the field's gradual shift toward precision microbiome modulation and individualized interventions for metabolic and inflammatory disorders.Finally, eight articles explored non-traditional and emerging taxa, including Enterococcus, Blautia, Weizmannella, and even fungal candidates such as Aspergillus. Examples include the characterization of Blautia producta for its anti-inflammatory effects (Chen et al., 2025) and Enterococcus casseliflavus for its safety profile and immunoregulatory potential (Li et al., 2025). These contributions highlight the expanding search for alternative probiotics beyond the traditional lactobacilli and bifidobacteria.Taken together, the taxonomic distribution across this Research Topic reveals a dual narrative: the continued centrality of lactobacilli as model probiotics on the one hand, and on the other, the diversification of microbial candidates that may offer novel solutions to global health challenges. This balance underscores how probiotic science is simultaneously building on established foundations while opening to innovation and expansion into underexplored taxa.A major portion of recent studies in this Research Topic focused on the diverse functional roles of lactobacilli, reaffirming their centrality in probiotic science and their evolution into models for nextgeneration functional and therapeutic interventions. L. reuteri has demonstrated immunomodulatory effects in allergic diseases, restoring Treg/Th17 balance and identifying luteolin as a key anti-inflammatory metabolite (Zhang et al., 2025). Genomic and safety evaluations of Lcb. paracasei and Lcb. casei confirmed absence of virulence and AR genes, supporting their use in food and nutraceutical applications (Chen et al., 2025). Similarly, Lpb. plantarum L19 exhibits strain-specific antioxidant and stress resistance traits, highlighting its potential to mitigate oxidative stress, for example under heat stress in livestock (Wang et al., 2024). Comprehensive analyses of Lcb. paracasei LC86 and Lcb. casei LC89 further confirmed their safety through genomic and phenotypic assessments and in vivo acute toxicity studies (Chen et al., 2025). Beyond gastrointestinal health, lactobacilli have shown potential to adsorb microplastics and reduce intestinal accumulation and inflammation (Teng et al., 2025), and to reinforce the host-pathogen interface by reducing Staphylococcus aureus and Escherichia coli adhesion and epithelial cell death (Kiousi et al., 2024). Encapsulation of probiotics and synbiotics has been highlighted as a strategy to enhance survival and expand applications in immune, metabolic, and neurological health (Sarita et al., 2024). Mechanistic studies on Lacticaseibacillus rhamnosus LRa05 showed modulation of cytokines, oxidative stress, and gut microbiota, while engineering of Lcb. paracasei EG005 to enhance superoxide dismutase activity illustrates precision probiotics with tailored antioxidant capacity (Dong et al., 2024;Kim et al., 2024). Other strains demonstrated targeted health effects, including prevention of constipation via microbiota modulation by Lcb. rhamnosus Glory LG12 (Ma et al., 2025), biofilm formation and antioxidant activity of Ligilactobacillus salivarius LS-ARS2 (Patra et al., 2025), and mitigation of heat stress in dairy cows by Lpb. plantarum L19 (Wang et al., 2024). Lpb. plantarum strains ONU 12 and ONU 355, along with Lcb. casei ATCC 393, inhibited hepatocellular carcinoma and cholangiocarcinoma cell proliferation, synergized with chemotherapeutics, and induced apoptosis and senescence (Duduyemi et al., 2024). Lcb. casei KACC92338 exhibited antioxidant, stress-tolerance, and antimicrobial properties with genomic safety, highlighting its probiotic potential (Kandasamy et al., 2024).These studies confirm the central role of lactobacilli while showing their expanding applications, from allergy and oncology to environmental health, within the broader One Health framework.The genus Bifidobacterium is a cornerstone of the gut microbiota in early life and remains a central focus in probiotic research due to its strain-specific roles in maintaining intestinal and systemic health. Among the reviewed works, Bifidobacterium spp. demonstrates key physiological effects including enhancement of mucosal barrier integrity, immune modulation, and antagonism toward pathogenic microbes. These studies highlight diverse therapeutic potential, ranging from the alleviation of metabolic and neuroinflammatory markers to the improvement of inflammatory bowel disease when Bifidobacterium animalis subsp. lacti XLTG11 was combined with mesalazine, resulting in superior anti-inflammatory and microbiota-modulating effects compared to either treatment alone. Furthermore, several works explore synergistic combinations of Bifidobacterium spp. with other probiotics/prebiotics (Ma et al., 2024), suggesting that multi-strain or synbiotic formulations may provide enhanced outcomes. Taken together, the current evidence consolidates the position of Bifidobacterium spp. as crucial contributors to gut-brain and gut-immune homeostasis, underlining their future relevance in both clinical and functional food applications.Seidler et al. provided a comprehensive review of the postbiotic potential of Aspergillus oryzae, traditionally used in East Asian food fermentation, highlighting its ability to modulate the gut microbiome, enhance epithelial barrier function, influence immune responses, and impact metabolic and neural signaling. This work underscores the translational potential of fungal-derived postbiotics for gut health and related therapeutic interventions, while emphasizing the importance of standardization and quality control. Blautia producta 1009924, isolated from human feces, exhibits notable probiotic potential (Chen et al., 2025). In a DSS-induced zebrafish intestinal inflammation model, it reduced ROS production, modulated TLR4/NF-κB signaling, decreased pro-inflammatory cytokines, and enhanced SCFA levels, improving intestinal tissue integrity. Similarly, E. casseliflavus SHAMU-QH-02, isolated from the human biliary tract, shows broad-spectrum antagonistic activity, antioxidant and antiinflammatory effects, and safety for functional applications (Li et al., 2025). Recent genome sequencing of four Akkermansia spp. human isolates revealed low genetic risk, with limited AR and virulence genes, and functional annotations enriched in metabolic pathways. These strains support gut barrier integrity, modulate host metabolism, and influence immune signaling, highlighting their potential for precision microbiome-targeted interventions in metabolic and inflammatory disorders (Lu et al., 2024). Weizmannella coagulans BC99 exhibits notable probiotic and anti-inflammatory properties (Gao et al., 2024). In a Caenorhabditis elegans hyperuricemia model, it reduced uric acid and xanthine oxidase levels, decreased ROS production, and improved lifespan and motility. Mechanistically, it activates DAF-16 and SKN-1 transcription factors, enhancing stress-response gene expression and antioxidant enzyme activity. Metabolomic analysis indicated regulation of amino acid, glycerophospholipid, and purine metabolism. These findings support W. coagulans BC99 as a safe and effective candidate for managing hyperuricemia and related metabolic disturbances.Peng et al. demonstrated that the probiotic Bacteroides fragilis (BF839), extensively used in China to alleviate gut microbiota dysbiosis, can enhance tumor sensitivity to immune checkpoint inhibitors (ICIs) via activation of the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) signaling pathway, suggesting that modulation of the gut microbiota with BF839 may represent a promising strategy to improve ICI efficacy in cancer therapy. Ma et al. reported that a synbiotic treatment combining low-, medium-, and high-dose mixed probiotics (Bifidobacterium animalis subsp. lactis XLTG11, Lcb. paracasei Glory LP16, Lpb. plantarum CCFM8661) with oligofructose alleviated DSS-induced colitis in mice by reducing inflammation, restoring colon length, enhancing intestinal barrier integrity, and increasing gut microbiota diversity and SCFA production, with therapeutic effects dependent on the probiotic dose. Synbiotic and multistrain formulations, combining Lactobacillus, Bifidobacterium, and Enterococcus species, have demonstrated enhanced probiotic efficacy (Liao et al., 2025;Ma et al., 2024;Teng et al., 2024). These combinations improve SCFA production, restore microbiota diversity, and suppress intestinal inflammation more effectively than single strains. Such synergistic interventions highlight the translational potential of multistrain probiotics for precision microbiome modulation and therapeutic applications in gastrointestinal health.In addition, several recent studies, while not directly testing probiotics, provide important insights into gut microbiota modulation and host health, which have clear implications for probiotic research. For example, supplementation with Portulaca oleracea (purslane) in aging rats improved gut morphology, increased fecal short-chain fatty acids, and shifted microbial composition by reducing Firmicutes and Fusobacteria while modulating metabolic pathways (Deng et al., 2025). These findings suggest that dietary interventions can target microbiota composition and metabolic output in ways similar to probiotic supplementation.Similarly, in the context of infectious diseases such as cholera, probiotics are highlighted as a potential adjunctive strategy to enhance gut barrier function, compete with pathogens, and modulate immunity, illustrating their translational potential even in settings traditionally managed by environmental or pharmacological interventions (Chowdhury et al., 2024).Other studies focus on functional metabolites like D-tryptophan, which exhibits antibacterial, immunomodulatory, and anti-biofilm properties (Wang et al., 2025), indicating that dietary or microbial-derived compounds can act synergistically with probiotics to improve host health.Clinical evidence further supports the use of probiotics and synbiotics in metabolic and liver diseases. In NAFLD patients, supplementation with probiotics or synbiotics significantly reduced liver enzymes, liver stiffness, insulin resistance, and BMI, highlighting their therapeutic efficacy (Song et al., 2025).Finally, Mendelian randomization studies linking gut microbiota with trimethylamine-N-oxide levels underscore specific microbial taxa that increase or decrease host susceptibility to metabolic risks (Yu et al., 2024). These mechanistic insights can inform the selection of probiotic strains aimed at modulating cardiovascular risk factors.The assembled articles within this Research Topic collectively highlight the evolution of probiotic research from mechanistic understanding to translational and industrial application. Key themes emerge across taxonomic groups, functional effects, and intervention strategies.A. muciniphila spp. (Lu et al., 2024), support intestinal homeostasis by enhancing epithelial integrity, reducing metabolic endotoxemia, and promoting anti-inflammatory signaling. Similarly, genera such as Blautia producta (Chen et al., 2025), W. coagulans (Gao et al., 2024), and E. casseliflavus SHAMU-QH-02 (Li et al., 2025) exert immunoregulatory and anti-inflammatory effects through SCFA production, ROS modulation, and cytokine regulation. In addition, B. fragilis BF839 has been extensively studied for its ability to modulate gut microbiota and enhance antitumor immunity (Peng et al., 2025). Lactobacillus johnsonii shows promise in digestive health by modulating immunity, enhancing gut barrier function, and maintaining microbiota balance, with future studies needed to clarify its mechanisms and provide experimental support for therapeutic applications (Zhou et al., 2025). In the MASH model, Lcb. rhamnosus GG (LGG) reduced pro-inflammatory cytokines, inhibited TGF-β/SMAD signaling, restored intestinal barrier integrity, and prevented endotoxin translocation, thereby alleviating liver inflammation and fibrosis (Wang et al., 2025).Spore-forming probiotics, exemplified by B. coagulans LMG S-31876 (Kallur et al., 2024), display high thermal stability and support host immunity, lipid metabolism, and stress-related outcomes, highlighting their suitability for robust industrial formulations.Next-generation probiotics, including A. muciniphila (Lu et al., 2024) and Faecalibacterium prausnitzii (Song et al., 2025), provide targeted modulation of gut mucosal integrity and SCFAdriven immune balance. Such approaches enable personalized microbiome interventions for metabolic and inflammatory disorders.Synbiotic and multistrain formulations incorporating Lactobacillus, Bifidobacterium, and Enterococcus species (Liao et al., 2025;Ma et al., 2024;Teng et al., 2024) enhance SCFA production, restore microbial diversity, and achieve superior inflammation suppression compared to monostrain interventions. These findings underscore the translational advantage of synergistic formulations for precision microbiota modulation.The field is moving toward practical application, emphasizing strain safety, viability, stability, scalability, and regulatory compliance. Techniques such as encapsulation, lyophilization, and prebiotic co-formulation improve functional performance and shelf stability (Liao et al., 2025;Song et al., 2025. Comprehensive safety profiling, as exemplified by E. casseliflavus SHAMU-QH-02, is critical for regulatory approval (Li et al., 2025).In conclusion, this Research Topic consolidates mechanistic, functional, and translational insights, highlighting the potential of probiotics to shape next-generation health interventions across clinical, nutritional, and industrial domains
BIOHEMIJSKA KARAKTERIZACIJA FAMILIJARNE HIPERHOLESTEROLEMIJE: POVEZANOST GENETIČKIH I LIPIDNIH PARAMETARA
No full textBackground: Familial hypercholesterolemia (FH) is characterised by elevated low-density lipoprotein cholesterol (LDL-C) levels and an increased risk of premature cardiovascular disease. The present study aimed to investigate the genetic background and associated biochemical profiles of patients with clinically suspected FH in Serbia. Methods: A total of 101 patients with clinically suspected FH were recruited between 2015 and 2023 from the Clinic for Endocrinology, Diabetes and Metabolic Diseases in Serbia. Clinical diagnosis was established using the Dutch Lipid Clinic Network (DLCN) criteria. Fasting serum lipids (total cholesterol [TC], LDL-C, high-density lipoprotein cholesterol [HDL-C], triglycerides [TG], apolipoprotein A-I [ApoA-I], apolipoprotein B [ApoB], and lipoprotein(a) [Lp(a)]) were measured enzymatically. Genetic testing for LDLR, APOB, PCSK9, and LDLRAP1 genes was performed using next-generation sequencing on the Illumina NextSeq 550DX platform. Variants were classified according to the American College of Medical Genetics and Genomics (ACMG) guidelines. Statistical analyses were conducted in SPSS (version 30.0).Results: Pathogenic or likely pathogenic variants were identified in 44 of 101 patients, yielding a mutation detection rate of 43.6%. Genetically confirmed FH patients exhibited significantly higher LDL-C (p<0.001), total cholesterol (p<0.001), triglycerides (p<0.001), and ApoB (p=0.001) compared with mutation-negative individuals, while HDL-C, ApoA-I (p=0.413), and Lp(a) (p=0.421) levels did not differ significantly between groups. Conclusions: This study demonstrates the molecular and biochemical diversity of familial hypercholesterolemia in the Serbian population. Pathogenic FH mutations were associated with higher LDL-C, total cholesterol, and ApoB levels, underscoring the importance of combining genetic testing with lipid profiling for precise diagnosis and management.Uvod: Familijarna hiperholesterolemija (FH) je bolest koju karakteri{u povi{eni nivoi lipoproteina niske gustine (LDLC) i pove}an rizik od prevremene kardiovaskularne bolesti. Cilj studije bio je da se ispita genetska osnova, prate}i biohemijski profili, klini~ke manifestacije i terapijski odgovor kod pacijenata sa klini~kom sumnjom na FH u Srbiji. Metode: Uklju~en je 101 pacijent, koji su pra}eni od 2015. do 2023. godine na Klinici za endokrinologiju, dijabetes i bolesti metabolizma. Klini~ka dijagnoza postavljena je prema kriterijumima Holandske lipidne mre`e (DLCN). Lipidi u serumu nata{te analizirani su enzimskim metodama, a geneti~ko testiranje sprovedeno je ranije metodom sekvenciranja nove generacije. Nivo serumskih lipida je upore|en kod pacijenata kod kojih je potvr|eno prisustvo varijanti u genima LDLR, APOB, PCSK9 i LDLRAP1, i onih koji su bili negativni u ovim analizama. Terapijski odgovor je pra}en preko postizanja ciljnih vrednosti LDL-C. Statisti~ke analize ura|ene su u programu SPSS 30.0. Rezultati: Geneti~ki potvr|eni FH pacijenti imali su zna~ajno vi{e vrednosti ApoB (p=0,001), dok se ApoA-I (p=0,413) i Lp(a) (p=0,421) nisu zna~ajno razlikovali izme|u grupa. Pacijenti koji su bili nosioci patogenih geneti~kih varijanti su imali manju verovatno}u da postignu ciljne vrednosti LDl-C posle terapije, u odnosu na one koji su bili negativni na geneti~kim testovima.Zaklju~ak: Ova studija potvr|uje molekularnu i biohemijsku raznovrsnost FH u srpskoj populaciji. Patogene geneti~ke varijante su povezane sa vi{im vrednostima ApoB, {to nagla{ava zna~aj integracije geneti~kog testiranja sa analizom lipidnog profila u dijagnostici i le~enju FH
Phenylbutyric Acid Modulates Apoptosis and ER Stress-Related Gene Expression in Glycogen Storage Disease Type Ib In Vitro Model
No full textIntroduction Chronic endoplasmic reticulum (ER) stress and increased apoptosis are involved in the pathogenesis of glycogen storage disease Ib (GSD Ib), whereas small molecule phenylbutyrate (4-PBA) showed the capability of reducing ER stress-induced apoptosis. The objective was to generate an in vitro system in which capability of small molecules (SMs) to influence ER stress and apoptosis could be screened at the expression level. Methods G6PT-deficient FlpInHEK293 cell line was created and validated using the CRISPR/Cas9 knockout method. Molecular markers of unfolded protein response (ATF4, DDIT3, HSPA5, XBP1s), and apoptosis (BCL2/BAX, CASP3, CASP7) in G6PT-deficient cells were analyzed using RT-qPCR method before and upon the treatment with 4-PBA. Results Treatment with the most effective dose of 1 mM 4-PBA reduced the expression of UPR markers and executioner caspases, while increased BCL2/BAX ratio in G6PT-deficient cells. Our results proved the concept that 4-PBA could alleviate markers of ER stress detected in the GSD Ib in vitro model system and prevent cell death. Conclusion This cost-effective in vitro model screens the therapeutic potential of SMs affecting ER stress and apoptosis in G6PT-deficient kidney cells, offering a first-line screening assay for promising compounds. 4-PBA's potential repurposing for GSD Ib patients opens new research directions.Supplementary material: [
Beneficial effects of Lactiplantibacillus plantarum BGPKM22 manifest only in interaction with healthy, but not with diseased human bronchial epithelial cells
No full textIt has already been recognised that lung microbiota differs in healthy and diseased lungs. In chronic obstructive pulmonary disease (COPD), a change in the structure, abundance and diversity of lung microbiota correlates with the severity of disease. But how the members of lung microbiota influence healthy and diseased lungs, as well as how they are affected by the lung health status is still largely unknown. In this study, we applied a dual RNA sequencing in order to scrutinise an early interspecies interaction between healthy and diseased human primary bronchial epithelial cells exposed to the beneficial bacteria Lactiplantibacillus plantarum BGPKM22. In healthy and diseased cells interaction with BGPKM22 led to a change in expression of 52 and 45 genes, respectively. The genes IQCN, LINC01554, KCNB1, and CDK7 indicated a specific response of human bronchial epithelial cells exposed to the BGPKM22 strain, regardless of the health status. Markedly more genes showed a change in expression in the BGPKM22 strain in interaction with healthy than with diseased cells, 486 and 101, respectively. Interaction with human bronchial epithelial cells caused a stress to bacteria, but the response of bacteria depended on the health status of the cells. The adhesion of the BGPKM22 strain was better to healthy, than to diseased cells. The fitness of the BGPKM22 strain increased only in interaction with healthy, but not with diseased cells. Remarkably, interaction with healthy, but not with diseased cells, stimulated the synthesis of exopolysaccharide layer of the strain BGPKM22. So, beneficial effects of bacteria can be diminished in interaction with diseased cells. Also, a lowered affinity of bacteria towards diseased environment can explain microbiota dysbiosis in the diseased lungs, such as lungs in patients with COPD
The ankrd1a participates in the regulation of muscle cell differentiation during adult zebrafish skeletal muscle repair zebrafish
No full textZebrafish repair skeletal muscle injury through an evolutionary conserved multi-step process that involves
activation of satellite-like cells, differentiation of progenitor cells into myocytes, and their fusion into
myotubes, followed by myotube maturation and myofiber hypertrophy. Coordination and timely
regulation of these events are essential for functional muscle recovery. Here we identify ankrd1a, a gene
responsive to muscle stress, as a new player in the repair of adult zebrafish skeletal muscle and show its
involvement in modulating molecular mechanisms of myogenic cell differentiation. To assess the function
of ankrd1a in muscle healing we used the ankrd1a loss of the function mutant line generated by
CRISPR/Cas9 genome editing. It exhibited 4 bp deletion in exon 4, leading to the formation of a premature
stop codon. The predicted protein product lacks ankyrin repeats, which are essential for its function. We
showed that loss of ankrd1a function affected muscle repair in adult zebrafish. Although both ankrd1a
mutant and wt were actively repairing the injury, the wounded area in mutant appeared smaller than the
injured area in wt at 7 dpi. Moreover, the maturation of newly forming muscle fibers in the ankrd1a mutant
was delayed according to the expression of maturation marker myoz3a. In injured wt zebrafish, the
myoz3a expression profile resembled the one seen during the mouse muscle repair. In the mutant,
myoz3a was not responding to the injury in the same way, suggesting that ankrd1a regulates the
expression of at least this maturation marker. Next, by transcriptome profiling, we identified potential
targets of ankrd1a involved in skeletal muscle repair. RNA-seq was performed on samples collected at 5
dpi, in the stage of myogenic differentiation marked by upregulation of myogenin expression in both
injured ankrd1a mutant and wt muscle to a similar level. Loss of ankrd1a function caused changes in the
expression of genes related to muscle contraction, muscle cell differentiation, myocyte fusion, including
actin cytoskeleton organization and cell adhesion, and MAPK signaling pathway. All this suggested
accelerated myogenic differentiation and faster muscle injury repair in ankrd1a mutant compared to wt.
This hypothesis was tested by comparing birefringence intensity in the larvae's injured (and adjacent
uninjured) somites. On the fourth day post-injury, mutant larvae recovered more injured muscle than wt
larvae. Taken together, our results imply that in injured skeletal muscle ankrd1a protects repairing muscle
tissue from premature differentiation of newly forming myofibers, which may affect functional muscle
recovery.Abstract book: 7th European Zebrafish PI Meeting, Paris Brain InstituteApril 2 - 5, 202