Biology subjects

Che, S.

Publications and source records attributed to Che, S..

5 recordsLinked to original sources

bioRxiv2026

Engineered extracellular vesicles targeting BACE1 reduces amyloid beta plaque formation in a genetic mouse model of Alzheimer Disease

Alzheimers disease (AD) is a progressive neurodegenerative disorder characterized by the accumulation of amyloid-{beta} (A{beta}) plaques, neurodegeneration, and cognitive decline. {beta}-Site amyloid precursor protein cleaving enzyme 1 (BACE1) catalyzes the rate-limiting step in A{beta} production and remains a therapeutic target for AD. However, effective delivery of RNA therapeutics to the brain remains challenging due to the blood-brain barrier (BBB). Here, we evaluated the feasibility of using clinical-grade mesenchymal stem cell-derived extracellular vesicles (EVs) as systemic carriers for Bace1-targeting small interfering RNA (siRNA) in the 5xFAD mouse model of AD. Engineered EVs crossed the BBB and delivered siRNA cargo to the brain, with uptake observed in both neurons and astrocytes. Systemic therapy with EVs engineered to encapsulate Bace1 siRNA resulted in reduced brain Bace1 protein levels and a decrease in amyloid plaque burden compared with control EVs carrying scrambled siRNA. The reduction was most pronounced in larger, high-intensity plaques, suggesting that Bace1 suppression may preferentially limit plaque growth and maturation. Repeated systemic administration was well tolerated, with no evidence of treatment-associated toxicity. These findings establish a proof-of-concept feasibility for EV-mediated delivery of Bace1-targeting siRNA to the brain and support further development of engineered EVs as a therapeutic platform for neurodegenerative diseases. Future studies incorporating behavioral, molecular, and mechanistic analyses will be required to determine the extent to which Bace1 suppression delivered through EVs can modify disease progression and improve functional outcomes in AD.

cell biology↗

bioRxiv2026

Biotransformation and biodefluorination of chlorinated polyfluorocarboxylic acids by Acetobacterium species

Chlorinated per- and polyfluoroalkyl substances (Cl-PFAS) represent an important subgroup in replacement chemicals for legacy PFAS, and they have been detected in various environments including water bodies, soil, as well as air particles. However, the biodegradability of these chemicals is largely unknown. A recent study reported dechlorination triggered anaerobic biodefluorination of Cl-PFCAs by activated sludge communities. In this study, we further investigated the biodefluorination of Cl-PFCAs by pure cultures. Six of ten selected Cl-PFCAs displayed significant defluorination by Acetobacterium bakii, and corresponding pathways were proposed according to transformation product analysis. Several additional Acetobacterium species were all capable of defluorinating 3,5,7,8-tetrachloro-2,2,3,4,4,5,6,6,7,8,8- undecafluorooctanoic acid (CTFE4) with >50% removal of organic fluorine. On the contrary, Clostridium homopropionicum cannot defluorinate CTFE4. Crude protein extraction experiment showed that the enzymes responsible for CTFE4 dechlorination and defluorination required anaerobic atmosphere to function. Differential gene expression was analyzed according to RNA sequencing analysis, and the results indicated vitamin B12 related enzymes may involve in CTFE4 dechlorination.

microbiology↗

bioRxiv2025

Polysialic Acid Presentation on Microporous Scaffolds Supports Neural Repair after Ischemic Stroke

Recovery following ischemic stroke remains limited due to insufficient neural regeneration. Polysialic acid (PSA), a glycan prominently expressed during neural development, modulates neural progenitor cell (NPC) plasticity and migration, but its therapeutic potential in biomaterial-based stroke therapies remains underexplored. In this study, microporous annealed particle (MAP) scaffolds conjugated with PSA (PSA-MAP) were engineered to regulate NPC fate and promote neural tissue regeneration after stroke. PSA-MAP increased the presence of Sox2-positive progenitor cells within infarct and peri-infarct regions and elevated axonal content (NF200) in the lesion, while astrocytic and vascular coverage were not detectably changed at this early stage. In addition, 3D NPC cultures in MAP showed that tethered PSA alters NPC behavior over time, with reduced progenitor marker expression and PSA-dependent shifts in morphology, consistent with progression away from a progenitor state. Together, these data identify a glycan-forward, neuro-first repair route in which PSA-MAP enhances early neural regeneration without requiring concomitant angiogenic expansion, establishing PSA-MAP as a targeted biomaterial approach for endogenous neural repair after ischemic stroke.

bioengineering↗

bioRxiv2025

Polysialic Acid-Functionalized MAP Scaffolds Promote Regulatory Immune Responses After Ischemic Stroke

Glycosylation regulates immune and neural functions within the central nervous system (CNS), yet biomaterials rarely leverage glycans due to their structural complexity. Polysialic acid (PSA), comprising 2,8-linked sialic acid residues, is a promising candidate owing to its potent immunomodulatory interactions with inhibitory Siglec receptors. Systematic screening of multiple sialic acid derivatives identifies PSA as uniquely effective in inducing anti-inflammatory polarization of bone marrow-derived macrophages (BMDMs). Based on these findings, an injectable microporous annealed particle (MAP) scaffold presenting PSA covalently via its reducing end (MAP-PSA) is engineered, recapitulating physiological glycan orientation. MAP-PSA exhibits robust mechanical properties, stable glycan immobilization, and resistance to enzymatic degradation. Using ischemic stroke as a CNS injury model, MAP-PSA significantly reduces neutrophil infiltration and inflammatory activation while enhancing reparative macrophage and microglial phenotypes. These immunomodulatory effects persist into subacute stages, characterized by sustained reductions in inflammation and enhanced microglial homeostasis. Overall, MAP-PSA scaffolds demonstrate a novel therapeutic paradigm for CNS injuries such as stroke, with translational potential for broader neuroinflammatory and regenerative applications.

bioengineering↗

bioRxiv2023

Electron-bifurcation and fluoride efflux systems in Acetobacterium spp. drive defluorination of perfluorinated unsaturated carboxylic acids

Enzymatic cleavage of C-F bonds in per- and polyfluoroalkyl substances (PFAS) is largely unknown but avidly sought to promote systems biology for PFAS bioremediation. Here, we report the reductive defluorination of , {beta}-unsaturated per- and polyfluorocarboxylic acids by Acetobacterium spp. Two critical molecular features in Acetobacterium species enabling reductive defluorination are (i) a functional fluoride efflux transporter (CrcB) and (ii) an electron-bifurcating caffeate reduction pathway (CarABCDE). The fluoride transporter was required for detoxification of released fluoride. Car enzymes were implicated in defluorination by the following evidence: (i) only Acetobacterium spp. with car genes catalyzed defluorination; (ii) caffeate and PFAS competed in vivo; (iii) models from the X-ray structure of the electron-bifurcating reductase (CarC) positioned the PFAS substrate optimally for reductive defluorination; (iv) products identified by 19F-NMR and high-resolution mass spectrometry were consistent with the model. Defluorination biomarkers identified here were found in wastewater treatment plant metagenomes on six continents.

microbiology↗