Biology subjects

Lozano, C.

Publications and source records attributed to Lozano, C..

4 recordsLinked to original sources

bioRxiv2025

Human Mediodorsal Thalamus in Seizure Propagation

BackgroundHow different thalamic sites are recruited during seizure propagation remains poorly understood. Simultaneous recordings from multiple thalamic sites in patients with focal seizures provide a rare opportunity to investigate the spatiotemporal pattern of thalamic involvement during human epilepsy. ObjectiveTo characterize the recruitment patterns of mediodorsal (MD) thalamic subregion during seizures and their generalization to the contralateral hemisphere. MethodsWe analyzed 119 seizures from 23 patients (12 male, age range: 20-57y) undergoing multisite thalamic recordings. In accordance with current clinical standards, we determined the spatial and temporal features of thalamic seizure activity by visually reviewing intracranial EEG recordings from different seizure types in each individual patient. ResultsThe procedure of multisite thalamic recordings had no complications. In total, we captured seizures originating from temporal lobes (63%), orbitofrontal (11%), frontotemporal (8%), occipital (8%), lateral frontal (4%), parietal (3%), and cingulate (2%) regions. Seizures were focal (76% in 21 patients), focal-to-bilateral tonic-clonic (FBTC, 9% in nine patients), or only electrographic (15% in six patients). Thalamic engagement was seen in 100% of patients occurring typically early during seizure evolution (83% within 15 seconds of seizure onset). Majority of FBTC seizures (73%) had faster thalamic recruitment, often within the first 5 seconds. The pulvinar (PLV) subregion was the most common first-activated thalamic site, particularly in temporal lobe seizures. Although the MD was involved in most seizures (88.2%), it was rarely the initial or sole thalamic structure engaged and more often followed anterior (ANT) and/or PLV sites. Contralateral propagation occurred in 66% of seizures and was strongly linked to MD involvement: the ipsilateral and contralateral MDs were engaged in about 95% of these cases. When ipsilateral MD engagement was absent, contralateral spread of seizures was uncommon. In majority of seizures (60%) that generalized to the contralateral hemisphere, the ipsilateral MD was involved before or simultaneously with the contralateral cortical sites. Importantly, seizures that first activated the MD originated mainly from the medial temporal lobes, whereas those spreading primarily to the contralateral cortex were mostly neocortical in onset. ConclusionsThe thalamic MD subregion was often involved after the other thalamic sites, but the MD sites, along with the massa intermedia connecting the two thalami, were significantly involved when seizures spread to contralateral hemisphere. Our findings suggest that a single thalamic lead capturing both MD subregions may yield important clinical information about laterality, origin, and generalization of seizures.

neuroscience↗

bioRxiv2025

Autoimmunity and H. pylori infection cooperatively promote epithelial tumorigenic differentiation and systemic immune modulation

Background and AimsGastric cancer (GC) demographics have shifted, with a growing impact on younger populations, particularly women. Chronic Helicobacter pylori (HP) infection is the leading risk factor for GC; however, decreasing HP prevalence means it is unlikely the cause of rising incidence of early-onset GC. Autoimmunity, which is more prevalent in women, has been proposed as a contributing factor. As autoimmunity prevalence increases, HP and gastric autoimmunity are likely to converge within one individual. This study aimed to examine how combinatorial HP infection and autoimmunity affect tumorigenesis and the immune landscape. MethodsA mouse model mimicking human CTLA4 insufficiency and its risk of autoimmunity-driven GC development, CTLA4KD, was infected with HP strain PMSS1 by oral gavage. Tumorigenesis was histologically assed. Hematopoietic and non-hematopoietic cells were analyzed using 40-color spectral flow cytometry. Human PBMCs were co-cultured with HP, followed by flow cytometry and qRT-PCR for gene expression of sorted PBMC subsets. ResultsHP infection in CTLA4KD mice advanced dysplasia and increased tertiary lymphoid structures within the gastric mucosa. Loss of E-Cadherin and DMBT1 was exacerbated in the combinatorial setting of autoimmunity and HP infection. In the innate immune system HP and autoimmunity showed an additive effect in systemic NK cell decreases. In the adaptive immune system, HP and autoimmunity cooperatively elevated the proportion of CD4+Foxp3- cells expressing the transcription factor Helios, persisting 6-8 months post infection. The Helios-expressing CD4 cells co-expressed inhibitory markers PD-1, CD200 and CD39. ConclusionAutoimmunity and HP infection cooperatively elicit long-lasting suppression of innate and adaptive immunity while promoting epithelial tumorigenic differentiation in the stomach. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=77 SRC="FIGDIR/small/690054v1_ufig1.gif" ALT="Figure 1"> View larger version (17K): org.highwire.dtl.DTLVardef@1096623org.highwire.dtl.DTLVardef@1099e7org.highwire.dtl.DTLVardef@1e8493forg.highwire.dtl.DTLVardef@120e5d3_HPS_FORMAT_FIGEXP M_FIG C_FIG Background and contextAutoimmunity is emerging as a contributing factor for early-onset gastric cancer especially in young women, but it is unknown how it interacts with the most prevalent etiology factor, Helicobacter pylori. New findingsThis study provides the initial evidence that Helicobacter pylori and autoimmunity cooperatively cause long-lasting suppression of innate and adaptive immunity while promoting epithelial tumorigenic differentiation in the stomach. LimitationsEven with the murine-adapted Helicobacter pylori strain PMSS1, a human pathogen, the mouse modeling remains technically and conceptually challenging and can only capture some aspects of human Helicobacter pylori infection. Clinical research relevanceThis study showcases how autoimmunity predisposed by host genetics may cooperate with a prevalent environment factor, Helicobacter pylori, to promote gastric cancer development, with cellular and histopathological changes in the stomach, as well as local and systemic alteration of immune profiles. The lasting effects long after the elimination of Helicobacter pylori suggest the necessity of remedies besides Helicobacter pylori eradication. Basic research relevanceThis study provides molecular and cellular clues for how a convergence of autoimmunity and Helicobacter pylori cooperatively downregulates tumor suppressors in gastric epithelial cells while causing long-lasting suppression of innate and adaptive immunity. More studies are needed for better understanding of the interaction between Helicobacter pylori and autoimmunity, to help develop interventions against the alarming trend of early-onset gastric cancer. Lay summaryThis study provides initial insight into how autoimmunity and Helicobacter pylori in combination may impinge on multi-pronged effect on the stomach and the immune system to accelerate gastric cancer development.

cancer biology↗

bioRxiv2022

Specific targeting of inflammatory osteoclastogenesis by the probiotic yeast S. boulardii CNCM I-745 reduces bone loss in osteoporosis

Bone destruction is a hallmark of chronic inflammation, and bone-resorbing osteoclasts arising under such a condition differ from steady-state ones. However, osteoclast diversity remains poorly explored. Here, we combined transcriptomic profiling, differentiation assays and in vivo analysis in mouse to decipher specific traits for inflammatory and steady state osteoclasts. We identified and validated the pattern-recognition receptors (PRR) TLR2, Dectin-1 and Mincle, all involved in yeast recognition as major regulators of inflammatory osteoclasts. We showed that administration of the yeast probiotic Saccharomyces boulardi CNCM I-745 (Sb) in vivo reduced bone loss in OVX but not sham mice by reducing inflammatory osteoclasts. This beneficial impact of Sb is mediated by the regulation of the inflammatory environment required for the generation of inflammatory osteoclasts. We also showed that Sb derivatives as well as agonists of TLR2, Dectin-1 and Mincle specifically inhibited directly the differentiation of inflammatory but not steady state osteoclasts in vitro. These findings demonstrate a preferential use of the PRR-associated costimulatory differentiation pathway by inflammatory osteoclasts, thus enabling their specific inhibition, which opens new therapeutic perspectives for inflammatory bone loss.

physiology↗

bioRxiv2020

Competition and Caries on Enamel of a Dual-species Biofilm Model of Streptococcus mutans and Streptococcus sanguinis.

Imbalances within the dental biofilm trigger dental caries, currently considered a dysbiosis and the most prevalent non-communicable disease. There is still a gap in knowledge about the dynamics of enamel colonization by bacteria from the dental biofilm in caries. The aim, therefore, was to test whether the sequence of enamel colonization by a typically commensal and a cariogenic species modifies biofilms cariogenicity. Dual-species biofilms of Streptococcus mutans (Sm) and Streptococcus sanguinis (Ss) on saliva-coated enamel slabs were inoculated in different sequences: Sm followed by Ss (Sm-Ss), Ss followed by Sm (Ss-Sm), Sm and Ss inoculated at the same time (Sm=Ss) and the single-species controls Sm followed by Sm (Sm-Sm) and Ss followed by Ss (Ss-Ss). Biofilms were exposed to 10% sucrose, 3x/day for 5 days and the slabs/biofilms were retrieved to assess demineralization, viable cells, biomass, proteins, polysaccharides and H2O2 production. When compared with Sm-Sm, primary inoculation with Ss reduced demineralization (p<0.05). Both Ss-Sm and Sm=Ss sequences showed reduction in biomass, protein and polysaccharide content (p<0.05). The highest S. sanguinis viable cells and H2O2 production and the lowest acidogenicity were observed when Ss colonized enamel before Sm (p<0.05). Initial enamel adherence with commensal biofilms seems to induce more intense competition against more typically cariogenic species, reducing cariogenicity. ImportanceThe concept of caries as an ecological disease implies the understanding of the intricate relationships among the populating microorganisms. Under frequent sugars exposure, some the bacteria from the oral biofilm develop pathogenic traits that lead to oral imbalances, known as dysbiosis. Depending on which microorganism colonizes the dental surface first, different competition strategies may be developed. Since the study of the interactions in the entire dental biofilm is not an easy task, in this article we model the interplay among these microorganisms using a caries-inducing (S. mutans) and a health-associated species (S. sanguinis). Initial enamel adherence with S. sanguinis seems to induce more intense competition against more typically caries-inducing species. Besides continuous exposure with sugars, early colonization of the enamel by highly cariogenic species, like S. mutans, appears to be needed to develop caries lesions, as well. Promoting early colonization by health-associated bacteria, such as S. sanguinis, could help maintaining oral health, delaying dysbiosis.

microbiology↗