Biology subjects

Ceci, A.

Publications and source records attributed to Ceci, A..

4 recordsLinked to original sources

bioRxiv2026

A temporally regulated miRNA signature in pancreatic cancer extracellular vesicles disrupts the circadian clock and promotes muscle atrophy

Pancreatic ductal adenocarcinoma (PDAC) carries a dismal prognosis, aggravated by cachexia, a systemic wasting syndrome whose molecular mediators remain incompletely defined. Circadian disruption is a further hallmark of PDAC, yet a shared mechanistic basis between these two features has not been established. Here we show that the PDAC secretome, and the small extracellular vesicles (sEVs) it carries, are sufficient to disrupt the circadian clock in independent reporter cell lines and in differentiated myotubes, and to induce myotube atrophy. PANC-1 sEV release and miRNA cargo display pronounced time-of-day variation, with the cargo resolving into two functionally distinct pools: a rhythmically secreted subset, whose release is phase-coordinated and which transmits time-of-day information to the recipient tissue, and a constitutively secreted subset that, although non-rhythmic at the source, is itself capable of perturbing the recipient circadian clock. Individual miRNAs drawn from both pools exert distinct and non-redundant effects on circadian period and myotube diameter. Seahorse extracellular flux analysis further reveals that these miRNAs reprogram mitochondrial respiration and substrate utilization along three divergent trajectories, energetic, high-metabolic, and glycolytic, rather than along a single bioenergetic axis. Intersecting the tumor sEV secretome with serum sEV miRNAs from a pancreatic cancer patient cohort and with the miRNA-Seq landscape of 495 PDAC tumors defines a stable, broadly tumor-abundant, patient-detectable miRNA signature that collectively regulates circadian, proteostatic, and cachexia-relevant gene networks. Across these orthogonal datasets, hsa-miR-27b-3p emerges as a node within the rhythmically secreted pool: consistently detected in patient serum, ranked among the top 50 most abundant miRNAs in >90% of these tumors, and individually sufficient to shorten the circadian period, drive myotube atrophy comparable to dexamethasone, and impose an energetic mitochondrial phenotype. Together, these findings identify PDAC sEV miRNAs as temporally organized mediators coupling circadian disruption, muscle bioenergetics, and cachexia-relevant muscle reprogramming.

cell biology↗

bioRxiv2026

Circadian Disruption Drives Extracellular Matrix Remodeling to Facilitate Pulmonary Metastatic Colonization

Circadian clocks impose temporal architecture on signaling networks, and disruption of this architecture predisposes to cancer metastasis. Through direct pharmacological and genetic perturbation of core clock components, we establish that circadian desynchronization in mouse lung fibroblasts eliminates temporal migration gating, creating constitutive motility responses to TNF- and TGF-{beta}, and identify YAP/TEAD as the obligate, non-redundant convergence node through which clock-regulated ECM mechanical signals and cytokine-driven transcriptional programs jointly drive cellular motility. Chronic jet lag (CJL) in mice generates nocturnal TNF- elevation (ZT12-21) that drives sustained matrix metalloprotease expression while simultaneously reorganizing Hippo and TGF-{beta} signaling toward temporal convergence during daytime hours, enabling YAP/TEAD-dependent transcription to synergize with TGF-{beta} signaling and drive epithelial-to-mesenchymal transition (EMT) programs that normally remain temporally restricted. Functional validation demonstrates CJL doubles metastatic colonization incidence (40% to 90%) following B16F10 melanoma inoculation. Critically, established metastases amplify these molecular changes: metastatic burden under CJL creates maximal TGF-{beta} expression (ZT15-21), constitutive YAP activity, and sustained EMT marker expression, while eliminating M1/M2 macrophage temporal organization. Analysis of TCGA-SKCM metastatic melanoma datasets confirms that clock-disrupted human tumors exhibit selective strengthening of YAP/TAZ, EMT, and inflammatory pathway coupling, establishing that this convergence architecture is conserved in human disease. Together, these findings demonstrate that circadian disruption transforms from a facilitator of initial metastatic colonization into a driver of progressive metastatic burden by eliminating the temporal segregation that normally constrains pro-metastatic programs to discrete, non-overlapping windows, creating self-perpetuating cycles wherein pathway convergence facilitates colonization and established tumors amplify pro-metastatic signaling to maintain permissive microenvironmental conditions.

cancer biology↗

bioRxiv2022

Wildlife exposure to SARS-CoV-2 across a human use gradient

Pervasive SARS-CoV-2 infections in humans have led to multiple transmission events to captive animals. While SARS-CoV-2 has a potential broad wildlife host range, most documented infections to date are found in a single species, the white-tailed deer. The extent of SARS-CoV-2 exposure among wildlife species and the factors that influence wildlife transmission risk remain unknown. We sampled 23 wildlife species for SARS-CoV-2 and examined the effects of urbanization and human use on seropositivity. Here, we document positive detections of SARS-CoV-2 RNA in six species, including the deer mouse, Virginia opossum, raccoon, groundhog, Eastern cottontail, and Eastern red bat. In addition, we found that sites with high human activity had three times higher seroprevalence than low human-use areas. We detected SARS-CoV-2 genomic sequences from nine individuals of six species which were assigned to seven Pango lineages of the Omicron variant. The close match to variants circulating in humans at the time suggests at least seven recent human-to-animal transmission events. Our data support that exposure to SARS-CoV-2 has been widespread in wildlife communities and suggests that areas with high human activity may serve as points of contact for cross-species transmission.

ecology↗

bioRxiv2022

ANTARCTIC FUNGI: A BIO-SOURCE ALTERNATIVE TO PRODUCE POLYUNSATURATED FATTY ACIDS (PUFAs)

The Antarctic ecosystem is a combination of conditions including extremely low values of temperature. The environmental temperature is one of the parameters thoroughly affecting the structure and composition of fungal membranes lipids. The psychrophilic fungi generally increase the disorder within macromolecules to maintain membrane fluidity at low temperatures. The strategy adopted by Antarctic fungi is to increase the proportion of unsaturated fatty acid that allows maintaining a semi-fluid state of the membranes. This ecological feature might be exploited for using Antarctic fungi as potential alternative source of polyunsaturated fatty acids (PUFAs) for human diet. This study provides both the characterization of fungal strains isolated from Antarctica by lipidomic analysis and the laboratory/large-scale production of fungal biomass with high content of beneficial PUFAs. In detail, three fungal species isolated from environmental matrices from Antarctica were tested and identified at genome level. Growth experiments to evaluate the influence of temperature and substrate in the yield in biomass and unsaturated fatty acid (UFA) were conducted. The results showed that the selected fungi have a high percentage of UFA compared to saturated ones; low growth temperatures increase the yield in linolenic fatty acid (C18:3); the biomass yield depends on the composition of the growth substrate and a satisfying qualitative-quantitative yield has also been obtained by using an agri-food chain waste product as growth substrate. IMPORTANCEThe presence of polyunsaturated fatty acids (PUFAs) in human and animal diet is gaining attention because PUFAs have several recognized functional properties: they modulate immune response, have anti-allergic and anti-inflammatory activity, cardio-protective effect and reduce blood LDL cholesterol levels. Human diets typically do not contain sufficient PUFAs because foods rich in PUFAs are few and it is therefore necessary to supplement this diet. Food supplements with these types of fatty acid currently commercially available come from marine fish oils and this source is no longer sustainable. It is necessary to develop efficient industrial processes capable of producing good quality PUFAs and in quantity, even using as carbon and nitrogen sources agro-industrial chains (in our case spent yeast from brewing and whey waste) waste products. Like microorganisms we used Antarctic fungi because they are adapted at very low temperature increasing the proportion of unsaturated fatty acid that allows maintaining a semi-fluid state of the membranes.

ecology↗