Hellen Paula Valerio

Chronic inflammatory signaling contributes to cartilage degeneration across multiple joint diseases, yet the molecular consequences of sustained cytokine exposure remain incompletely understood. We investigated how prolonged interleukin-1β (IL-1β) stimulation remodels the chondrocyte proteome and whether these changes are associated with senescence-associated traits. Primary human articular chondrocytes were exposed to IL-1β (10 ng/mL) for up to four days. Time-resolved data-independent acquisition (DIA) proteomics was integrated with immunofluorescence, quantitative PCR, multiplex metalloproteinase profiling, BrdU incorporation, growth-curve analysis, and senescence-associated β-galactosidase assays. Sustained IL-1β induced extensive time-dependent proteomic remodeling, with early inflammatory and extracellular matrix responses followed by alterations in cell-cycle regulation and cytoskeletal organization. Prolonged stimulation was associated with persistent downregulation of CDK4, Cyclin D1, DNA replication-associated proteins, and Rho GTPase-associated components, accompanied by actin cytoskeletal remodeling. These molecular changes were associated with impaired proliferation, increased senescence-associated β-galactosidase activity, and transient modulation of p21. Following cytokine withdrawal, BrdU incorporation showed partial recovery. Together, these findings indicate that sustained IL-1β progressively reshapes the chondrocyte cellular state through coordinated remodeling of proliferative, cytoskeletal, and metalloprotease programs while showing some degree of proliferative plasticity under the conditions tested.

Mitochondria are central hubs of antiviral immunity and cellular metabolism, yet the links between SARS-CoV-2–induced mitochondrial remodeling, antiviral gene regulation, and post-translational control remain incompletely understood. Here, we investigated mitochondrial–immune remodeling in SARS-CoV-2–infected lung-derived LC-HK2 cells at 48 and 96 h post-infection using confocal and high-content imaging, colocalization analysis, CellProfiler quantification, RT-qPCR, proteomics, cytokine profiling, and conditioned-medium analysis. Infection induced a time-dependent mitochondrial phenotype. At 48 hpi, cells displayed early mitochondrial stress and fission-associated signatures, including increased DRP1, transient upregulation of mitochondrial respiratory genes, and reduced MFN1/2. At 96 hpi, mitochondria shifted toward elongated perinuclear networks, accompanied by increased fusion/biogenesis markers and partial ISG15–MFN2 colocalization, indicating a spatial association between ISG15-related antiviral/stress responses and mitochondrial remodeling. Antiviral and ISG-related transcripts were consistently upregulated, but IFN-α2 secretion remained limited, suggesting partial uncoupling between antiviral transcriptional activation and downstream interferon output. SUMO2/3 was dynamically modulated and showed time-dependent colocalization with mitochondrial dynamics proteins and MAVS. Together, these data support a coordinated mitochondrial–immune regulatory axis involving mitochondrial remodeling, ISG15-associated responses, and SUMO-dependent regulation during SARS-CoV-2 infection.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive motor neuron degeneration and chronic neuroinflammation in the brain and spinal cord, involving complex interactions between neurons and immune cells. Carnosine (β-alanyl-L-histidine) has pathophysiological relevance due to its ability to detoxify reactive carbonyl species, including α,β-unsaturated aldehydes, scavenge free radicals, and chelate zinc. Additionally, carnosine has been proposed to function in the Central Nervous System as a reservoir of histidine for histamine synthesis. Here, we investigated the effects of carnosine supplementation in the cerebellum of SOD1G93A ALS rats using quantitative proteomics. Cerebellar carnosine levels were significantly increased following supplementation. Carnosine treatment broadly improve mitochondrial and vesicular protein networks and increased the abundance of glutamatergic and GABAergic receptor subunits compared with non-treated ALS animals. Pathway enrichment analyses identified significant modulation of Rab-mediated trafficking and neurotransmitter release cycles. Collectively, these findings indicate that carnosine promotes systems-level remodeling of mitochondrial and synaptic networks in relation to the untreated ALS group, supporting its potential as a multimodal therapeutic strategy in ALS

Bacterial outer-membrane vesicles (OMVs) mediate stress tolerance, biofilm formation, and interkingdom communication, but their role in beneficial endophytes remains underexplored. We isolated 11 non-redundant isolates associated with Bacillus, Enterococcus, Kosakonia and Kocuria from Agave tequilana seeds, identified by MALDI-TOF MS and 16S rRNA gene sequencing. We focused on the catalase-negative Enterobacter cloacae SEA01, which exhibits plant-promoting traits and support agave growth under nutrient-poor microcosms. In addition, this endophyte produces OMVs. Time-resolved SEM documented OMV release and cell aggregation within 9 h, followed by mature biofilms at 24 h with continued vesiculation. Purified OMVs (≈80–300 nm) contained extracellular DNA and were characterized by dynamic light scattering and UHPLC–ESI–QTOF-MS lipidomics. The OMV lipidome was dominated by phosphatidylethanolamine (~80%) and was enriched in monounsaturated fatty acids (16:1, 18:1), while the stress-associated cyclopropane fatty acids (17:1, 19:1) were comparatively retained in the whole-cell membranes; OMVs also exhibited reduced ubiquinone-8. SEA01 is catalase-negative, uncommon among plant-associated Enterobacter, suggesting a testable model in which oxidative factors modulate OMV output and biofilm assembly. These may have implications for recognition and redox signaling at the root interface. Future works should combine targeted proteomics/genomics with genetic or chemical disruption of catalase/OMV pathways.

The solar ultraviolet (UV) radiation that reaches the Earth is composed of 95% of UVA (320 to 400 nm) and 5% of UVB (280 to 320 nm) radiation. UVB is carcinogenic, generating potentially mutagenic DNA...