RESUMO
Extracellular vesicles (EVs) constitute a sophisticated molecular exchange mechanism highly regarded for their potential as a next-generation platform for compound delivery. However, identifying sustainable and biologically safe sources of EVs remains a challenge. This work explores the emergence of novel sources of plant and bacterial-based EVs, such as those obtained from food industry by-products, known as BP-EVs, and their potential to be used as safer and biocompatible nanocarriers, addressing some of the current challenges of the field. These novel sources exhibit remarkable oral bioavailability and biodistribution, with minimal cytotoxicity and a selective targeting capacity toward the central nervous system, liver, and skeletal tissues. Additionally, we review the ease of editing these recently uncovered nanocarrier-oriented vesicles using common EV editing methods, examining the cargo-loading processes applicable to these sources, which involve both passive and active functionalization methods. While the primary focus of these novel sources of endogenous EVs is on molecule delivery to the central nervous system and skeletal tissue based on their systemic target preference, their use, as reviewed here, extends beyond these key applications within the biotechnological and biomedical fields.
Assuntos
Bactérias , Sistemas de Liberação de Medicamentos , Vesículas Extracelulares , Plantas , Vesículas Extracelulares/metabolismo , Bactérias/metabolismo , Humanos , Plantas/metabolismo , Animais , Sistemas de Liberação de Medicamentos/métodos , Leveduras/metabolismo , Portadores de Fármacos/químicaRESUMO
PURPOSE: To determine the efficacy of different fragmentation patterns in femtosecond laser-assisted cataract surgery (FLACS) using Ziemer FEMTO LDV Z8. METHODS: We compared three different types of surgery: conventional cataract surgery (CCS), FLACS with conventional radial slices (named No-Spiderweb), and FLACS with a novel fragmentation pattern (radial slices combined with one or two rings) called "Spiderweb." Visual acuity (VA), nuclear opacity (NO) according to the Lens Opacities Classification System (LOCS lll), effective phacoemulsification time (EPT) and vacuum time were obtained for 845 eyes. RESULTS: Using FLACS (Spiderweb + No-Spiderweb), EPT was significantly reduced by 26% compared to CCS (FLACS: 2.46 ± 2.60 s; CCS: 3.34 ± 2.89 s; ΔM = - 0.88 s, p < .001). Furthermore, EPT as a function of progression of lens opacity was found to be not only lower in Spiderweb compared to CCS, but also in comparison with No-Spiderweb. At NO3, a significant reduction of 65% in EPT was observed by using Spiderweb compared to CCS (Spiderweb: 0.68 ± 1.23 s; CCS: 1.96 ± 1.53 s; ΔM = - 1.28 s, p <.001). Interestingly, EPT at NO3 was also significantly reduced by 57% in Spiderweb compared to No-Spiderweb (Spiderweb: 0.68 ± 1.23 s; No-Spiderweb: 1.57 ± 1 .59 s; ΔM = - 0.90 s, p <.001). The use of Spiderweb only marginally extends the vacuum time compared to No-Spiderweb by 11 s (Spiderweb: 209.13 ± 35.83 s; No-Spiderweb: 198.35 ± 36.84 s; p = .003) and the postoperative improved VA showed no significant difference among the different types of surgery (all ps ≥ .05). CONCLUSION: FLACS significantly reduces EPT compared to CCS. Furthermore, the novel Spiderweb pattern significantly reduces EPT in patients with a cataract of NO3 compared to CCS, but also to FLACS with the existing radial pattern (No-Spiderweb).
Assuntos
Extração de Catarata , Catarata , Terapia a Laser , Facoemulsificação , Humanos , Estudos Prospectivos , LasersRESUMO
We demonstrate a novel approach for controlling the line defect formation in microscopic wrinkling structures by patterned plasma treatment of elastomeric surfaces. Wrinkles were formed on polydimethylsiloxane (PDMS) surfaces exposed to low-pressure plasma under uniaxial stretching and subsequent relaxation. The wrinkling wavelength λ can be regulated via the treatment time and choice of plasma process gases (H2, N2). Sequential masking allows for changing these parameters on micron-scale dimensions. Thus, abrupt changes of the wrinkling wavelength become feasible and result in line defects located at the boundary zone between areas of different wavelengths. Wavelengths, morphology, and mechanical properties of the respective areas are investigated by Atomic Force Microscopy and agree quantitatively with predictions of analytical models for wrinkle formation. Notably, the approach allows for the first time the realization of a dramatic wavelength change up to a factor of 7 to control the location of the branching zone. This allows structures with a fixed but also with a strictly alternating branching behavior. The morphology inside the branching zone is compared with finite element methods and shows semi-quantitative agreement. Thus our finding opens new perspectives for "programming" hierarchical wrinkling patterns with potential applications in optics, tribology, and biomimetic structuring of surfaces.
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Nanophase mixtures, leveraging the complementary strengths of each component, are vital for composites to overcome limitations posed by single elemental materials. Among these, metal-elastomer nanophases are particularly important, holding various practical applications for stretchable electronics. However, the methodology and understanding of nanophase mixing metals and elastomers are limited due to difficulties in blending caused by thermodynamic incompatibility. Here, we present a controlled method using kinetics to mix metal atoms with elastomeric chains on the nanoscale. We find that the chain migration flux and metal deposition rate are key factors, allowing the formation of reticular nanophases when kinetically in-phase. Moreover, we observe spontaneous structural evolution, resulting in gyrified structures akin to the human brain. The hybridized gyrified reticular nanophases exhibit strain-invariant metallic electrical conductivity up to 156% areal strain, unparalleled durability in organic solvents and aqueous environments with pH 2-13, and high mechanical robustness, a prerequisite for environmentally resilient devices.
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Vascular dysfunction underlies the onset and progression of many life-threatening diseases, highlighting the need for improved understanding of its molecular basis. Here, we present differential systemic decellularization in vivo (DISDIVO), a protocol that enables systemic and independent study of the molecular changes in each vasculature layer in murine models of disease. We describe steps for anesthesia, perfusion surgery, and exsanguination. We then detail detachment and collection of glycocalyx and decellularization and collection of both endothelial and smooth muscle cells. For complete details on the use and execution of this protocol, please refer to Serra et al., Gallart-Palau et al., and Vinaiphat et al.1,2,3.
Assuntos
Miócitos de Músculo Liso , Animais , Camundongos , Modelos Animais de Doenças , PerfusãoRESUMO
Naturally acquired immunity to malaria develops only after years of repeated exposure to Plasmodium parasites. Despite the key role antibodies play in protection, the cellular processes underlying the slow acquisition of immunity remain unknown. Using mouse models, we show that severe malaria infection inhibits the establishment of germinal centers (GCs) in the spleen. We demonstrate that infection induces high frequencies of T follicular helper (Tfh) cell precursors but results in impaired Tfh cell differentiation. Despite high expression of Bcl-6 and IL-21, precursor Tfh cells induced during infection displayed low levels of PD-1 and CXCR5 and co-expressed Th1-associated molecules such as T-bet and CXCR3. Blockade of the inflammatory cytokines TNF and IFN-γ or T-bet deletion restored Tfh cell differentiation and GC responses to infection. Thus, this study demonstrates that the same pro-inflammatory mediators that drive severe malaria pathology have detrimental effects on the induction of protective B cell responses.