The scaffold-free tissue engineering using spheroids is pointed out as an approach for optimizing the delivery system of cartilage construct. In this study, we aimed to evaluate the micromolded ...nonadhesive hydrogel (MicroTissues®) for spheroid compaction (2-day culture) and spontaneous chondrogenesis (21-day culture) using cartilage progenitors cells (CPCs) from human nasal septum without chondrogenic stimulus. CPC spheroids showed diameter stability (486 μm ± 65), high percentage of viable cells (88.1 ± 2.1), and low percentage of apoptotic cells (2.3%). After spheroid compaction, the synthesis of TGF-β1, TGF-β2, and TGF-β3 was significantly higher compared to monolayer (p<0.005). Biomechanical assay revealed that the maximum forces applied to spheroids after chondrogenesis were 2.6 times higher than for those cultured for 2 days. After spontaneous chondrogenesis, CPC spheroids were entirely positive for N-cadherin, collagen type II and type VI, and aggrecan and chondroitin sulfate. Comparing to monolayer, the expression of SOX5 and SOX6 genes analyzed by qPCR was significantly upregulated (p<0.01). Finally, we observed the capacity of CPC spheroids starting to fuse. To the best of our knowledge, this is the first time in the scientific literature that human CPC spheroids were formed by micromolded nonadhesive hydrogel, achieving a successful scaffold-free cartilage engineering without chondrogenic stimulus (low cost).
We report the in vitro long-term (20 wk) changes in cells exposed to well-characterized gold nanoparticles (Au NPs) with varying shapes and surface coatings under both chronic (exposure to Au NPs ...continuously over 20 wk) and nonchronic (initial acute cell exposure to Au NPs, followed by 20 wk in NP-free cell media) conditions. Both chronic and nonchronic Au NPs exposures at low dose induce modifications at the gene level after long periods. In attempt to overcome from the injuries caused by nanoparticle exposure, genes related to oxidative stress, cell cycle regulation, and inflammation are among those presenting differential expression levels. Surprisingly, the nonchronic exposure induced more gene expression changes than its chronic counterpart and the stress effects caused by this type of exposure were sustained even after 20 wk without any additional NP exposure. NP surface chemistry played an important role in the alteration of gene regulation. Overall, our data suggest that (i) cells can adaptively respond to chronic, low-level NP insults; (ii) the cell stress response is not reversible over time upon removal of NPs upon acute, nonchronic exposure; and (iii) polyethylene glycol is not as benign a surface chemistry as is generally supposed.
Background
As the diagnosis of Parkinson's disease (PD) is fundamentally clinical, the usefulness of ioflupane (123I) single‐photon emission computed tomography (SPECT) or DaTSCAN as a diagnostic ...tool has been a matter of debate for years. The performance of DaTSCAN is generally recommended in the follow‐up of patients with a clinically uncertain diagnosis, especially in those with a suspected essential tremor, drug‐induced parkinsonism, or vascular parkinsonism. However, there is a dearth of DaTSCAN findings regarding neurodegenerative parkinsonisms besides PD and atypical parkinsonisms. To date, a specific nigrostriatal dopamine uptake pattern that would help differentiate PD from the most frequent atypical parkinsonisms is yet to be described. This fact is further complicated by the possible visualization of abnormalities in the uptake pattern in patients with rarer neurodegenerative parkinsonisms.
Objectives
We aimed to summarize the current literature regarding DaTSCAN findings in patients with rare neurodegenerative parkinsonisms.
Methods
The PubMed database was systematically screened for studies in English or Spanish up to October 15, 2023, using search terms “DaTSCAN”, “ioflupane”, “DaT‐SPECT”, “123I‐FP‐CIT SPECT”, “dopamine transporter imaging”, and “123I FP‐CIT SPECT”. Duplicated publications and studies regarding PD, atypical parkinsonisms, dystonia‐parkinsonism, essential tremor, and parkinsonism due to non‐degenerative causes were excluded.
Results
The obtained results were reviewed and summarized, including DaTSCAN findings in fragile X‐associated tremor/ataxia syndrome, prion diseases, Huntington's disease, spinocerebellar ataxia, hereditary spastic paraparesis, metabolic disorders, and other diseases (anti‐IgLON5 disease, ring chromosome 20 syndrome, chorea‐acanthocytosis, and neuronal ceroid lipofuscinosis).
Conclusions
This review highlights the need to determine in the future the utility and cost‐effectiveness of DaTSCAN, both as a diagnostic and a prognostic tool, in patients with parkinsonian symptoms in rare neurodegenerative diseases.
Breast cancer is a major cause of suffering and mortality among women. Limitations in the current diagnostic methods and treatment approaches have led to new strategies to positively impact the ...survival rates and quality of life of breast cancer patients. Nanotechnology offers a real possibility of mitigating breast cancer mortality by early-stage cancer detection and more precise diagnosis as well as more effective treatments with minimal side effects. The current nanoplatforms approved for breast cancer therapeutics are based on passive tumor targeting using organic nanoparticles and have not provided the expected significant improvements in the clinic. In this review, we present the emerging approaches in breast cancer nanomedicine based on active targeting using versatile inorganic nanoplatforms with biomedical relevance, such as gold, silica, and iron oxide nanoparticles, as well as their efficacy in breast cancer imaging, drug and gene delivery, thermal therapy, combinational therapy, and theranostics in preclinical studies. The main challenges for clinical translation and perspectives are discussed.
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•Mineral tailings from two copper mines were bioleached under different conditions.•Greatest copper extraction was achieved at extremely low pH, at 45°C and under oxidative/reductive ...conditions.•Copper present in tailings PLS was selectively precipitated as CuS by biogenic H2S.•Microbial communities were dominated by Sb. thermosulfidooxidans and Acidithiobacillus spp.•The microbial community composition was affected by temperature and the tailings used.
Waste materials from metal mining, such as mineral tailings, often contain significant amounts of potentially valuable metals particularly where, as in many historic operations, the efficiency of flotation technologies used to concentrate target minerals was not as good as those currently available. A two-stage mineral leaching and metal recovery protocol was developed to extract copper from tailings generated as waste materials in two mines currently operating in Spain and Serbia. The most effective extraction of copper (84 to >90%) was achieved by bioleaching the tailings at 45°C, using a defined microbial consortium, where elemental sulfur was added to the tailings and the pH of leach liquors allowed to fall to ∼pH 1, at which point anaerobic conditions were imposed. The thermo-tolerant acidophiles Acidithiobacillus caldus and Sulfobacillus thermosulfidooxidans emerged as the dominant bacteria present in both tailings leachates under these conditions. Copper present in the pregnant leach solutions (PLS) produced were next precipitated as a sulfide phase using hydrogen sulfide generated in a low pH (4.0) sulfidogenic bioreactor. The off-line system used allowed the copper present in PLS to be precipitated selectively without the need to adjust the pH of the PLS, though small amounts of silver present in PLS from one of the tailings samples co-precipitated with copper sulfide. Experimental data also suggested that it would be possible to extract silver from bioleached solid residues (where it was mostly found) using a simple chemical extractant. The results suggested that bio-processing these waste materials would have economic as well as environmental benefits.
As the diagnosis of Parkinson's disease (PD) is fundamentally clinical, the usefulness of ioflupane (
I) single-photon emission computed tomography (SPECT) or DaTSCAN as a diagnostic tool has been a ...matter of debate for years. The performance of DaTSCAN is generally recommended in the follow-up of patients with a clinically uncertain diagnosis, especially in those with a suspected essential tremor, drug-induced parkinsonism, or vascular parkinsonism. However, there is a dearth of DaTSCAN findings regarding neurodegenerative parkinsonisms besides PD and atypical parkinsonisms. To date, a specific nigrostriatal dopamine uptake pattern that would help differentiate PD from the most frequent atypical parkinsonisms is yet to be described. This fact is further complicated by the possible visualization of abnormalities in the uptake pattern in patients with rarer neurodegenerative parkinsonisms.
We aimed to summarize the current literature regarding DaTSCAN findings in patients with rare neurodegenerative parkinsonisms.
The PubMed database was systematically screened for studies in English or Spanish up to October 15, 2023, using search terms "DaTSCAN", "ioflupane", "DaT-SPECT", "123I-FP-CIT SPECT", "dopamine transporter imaging", and "123I FP-CIT SPECT". Duplicated publications and studies regarding PD, atypical parkinsonisms, dystonia-parkinsonism, essential tremor, and parkinsonism due to non-degenerative causes were excluded.
The obtained results were reviewed and summarized, including DaTSCAN findings in fragile X-associated tremor/ataxia syndrome, prion diseases, Huntington's disease, spinocerebellar ataxia, hereditary spastic paraparesis, metabolic disorders, and other diseases (anti-IgLON5 disease, ring chromosome 20 syndrome, chorea-acanthocytosis, and neuronal ceroid lipofuscinosis).
This review highlights the need to determine in the future the utility and cost-effectiveness of DaTSCAN, both as a diagnostic and a prognostic tool, in patients with parkinsonian symptoms in rare neurodegenerative diseases.
Gold nanoparticles (Au NPs) are attractive for biomedical applications not only for their remarkable physical properties, but also for the ease of which their surface chemistry can be manipulated. ...Many applications involve functionalization of the Au NP surface in order to improve biocompatibility, attach targeting ligands or carry drugs. However, changes in cells exposed to Au NPs of different surface chemistries have been observed, and little is known about how Au NPs and their surface coatings may impact cellular gene expression. The gene expression of two model human cell lines, human dermal fibroblasts (HDF) and prostate cancer cells (PC3) was interrogated by microarray analysis of over 14,000 human genes. The cell lines were exposed to four differently functionalized Au NPs: citrate, poly(allylamine hydrochloride) (PAH), and lipid coatings combined with alkanethiols or PAH. Gene functional annotation categories and weighted gene correlation network analysis were used in order to connect gene expression changes to common cellular functions and to elucidate expression patterns between Au NP samples. Coated Au NPs affect genes implicated in proliferation, angiogenesis, and metabolism in HDF cells, and inflammation, angiogenesis, proliferation apoptosis regulation, survival and invasion in PC3 cells. Subtle changes in surface chemistry, such as the initial net charge, lability of the ligand, and underlying layers greatly influence the degree of expression change and the type of cellular pathway affected.
Conspectus Plasmons, collective oscillations of conduction-band electrons in nanoscale metals, are well-known phenomena in colloidal gold and silver nanocrystals that produce brilliant visible colors ...in these materials that depend on the nanocrystal size and shape. Under illumination at or near the plasmon bands, gold and silver nanocrystals exhibit properties that enable fascinating biological applications: (i) the nanocrystals elastically scatter light, providing a straightforward way to image them in complex aqueous environments; (ii) the nanocrystals produce local electric fields that enable various surface-enhanced spectroscopies for sensing, molecular diagnostics, and boosting of bound fluorophore performance; (iii) the nanocrystals produce heat, which can lead to chemical transformations at or near the nanocrystal surface and can photothermally destroy nearby cells. While all the above-mentioned applications have already been well-demonstrated in the literature, this Account focuses on several other aspects of these nanomaterials, in particular gold nanorods that are approximately the size of viruses (diameters of ∼10 nm, lengths up to 100 nm). Absolute extinction, scattering, and absorption properties are compared for gold nanorods of various absolute dimensions, and references for how to synthesize gold nanorods with four different absolute dimensions are provided. Surface chemistry strategies for coating nanocrystals with smooth or rough shells are detailed; specific examples include mesoporous silica and metal–organic framework shells for porous (rough) coatings and polyelectrolyte layer-by-layer wrapping for “smooth” shells. For self-assembled-monolayer molecular coating ligands, the smoothest shells of all, a wide range of ligand densities have been reported from many experiments, yielding values from less than 1 to nearly 10 molecules/nm2 depending on the nanocrystal size and the nature of the ligand. Systematic studies of ligand density for one particular ligand with a bulky headgroup are highlighted, showing that the highest ligand density occurs for the smallest nanocrystals, even though these ligand headgroups are the most mobile as judged by NMR relaxation studies. Biomolecular coronas form around spherical and rod-shaped nanocrystals upon immersion into biological fluids; these proteins and lipids can be quantified, and their degree of adsorption depends on the nanocrystal surface chemistry as well as the biophysical characteristics of the adsorbing biomolecule. Photothermal adsorption and desorption of proteins on nanocrystals depend on the enthalpy of protein–nanocrystal surface interactions, leading to light-triggered alteration in protein concentrations near the nanocrystals. At the cellular scale, gold nanocrystals exert genetic changes at the mRNA level, with a variety of likely mechanisms that include alteration of local biomolecular concentration gradients, changes in mechanical properties of the extracellular matrix, and physical interruption of key cellular processeseven without plasmonic effects. Microbiomes, both organismal and environmental, are the likely first point of contact of nanomaterials with natural living systems; we see a major scientific frontier in understanding, predicting, and controlling microbe–nanocrystal interactions, which may be augmented by plasmonic effects.
Recent evidence suggests that genetic studies may contribute to a better understanding of individual susceptibility to caries. Matrix metalloproteinases (MMPs) and their tissue inhibitors have been ...suggested to be involved in the caries process. The purpose of this study was to determine if polymorphisms in MMP2 (rs243865), MMP9 (rs17576), MMP13 (rs2252070), and TIMP2 (rs7501477) were associated with caries. Eligible unrelated children and adolescents were evaluated using a cross-sectional design. Data on oral health habits was obtained through a questionnaire and caries data was collected by clinical examination. Genotyping of the selected polymorphisms was carried out by real-time PCR. Allele and genotype frequencies were compared between individuals with and without caries experience. Of 505 subjects, 212 were caries-free and most subjects (61.2%) had mixed dentition. Allele frequency of MMP2, MMP13 and TIMP2 was different between caries-affected and caries-free individuals, with significant association for MMP13 (p = 0.004). Mutant allele carriers for MMP13 demonstrated a significantly decreased risk for caries (OR = 0.538, 95% CI 0.313–0.926); this result remained significant after adjustment for candidate genes, type of dentition and dietary factors. Allelic and genotype frequencies of the polymorphism in MMP9 were similar in caries-affected and caries-free individuals. Genetic variations in MMP13 may contribute to individual differences in caries susceptibility. Our findings reinforce that susceptibility to caries results from gene-environment interactions.
•Regulated deficit irrigation (postharvest irrigation at 60% of the control) decreased vegetative plant growth of early nectarine.•Deficit irrigation increased crop WUE by 25% in 2010 and 2011, and ...by 74% in 2012.•Deficit irrigation did not alter physical and chemical characteristics of the fruit, or crop yield.
A three-year long experiment was implemented in an early nectarine (Prunus persica L. Batsch cv. Flanoba) commercial orchard to evaluate the effects of deficit irrigation and different crop levels on vegetative growth, plant water status, and fruit yield and quality. Three irrigation treatments were assessed: (i) control, full irrigation (TCTL); (ii) normal practice of the farmer (TFRM); and (iii) regulated deficit irrigation (TRDI), which involved irrigating the crop at the same level as the control (TCTL) during the critical periods of the first year and at 60% TCTL during postharvest. In the last two growing seasons the irrigation was scheduled to maintain the signal intensity (SI) of maximum daily trunk shrinkage (SIMDS=MDSTRDI/MDSTCTL) at different water stress levels depending on the phenological stage: SI=1.0 (non-water stress) and SI=1.4 (moderate water stress). Besides, during the last two seasons, the interactions between TCTL and TRDI were studied at five different crop levels, which were obtained by controlling the distance between fruits left on the branches: from very low (16cm between fruits) to very high (8cm between fruits). Crop water use efficiency (WUE) of TRDI was higher than in TCTL and TFRM, increasing by around 25% in 2010 and 2011, and around 74% the final year. Interestingly, TFRM increased the WUE from the first year by more than 30%. The yield/annual increase in trunk-cross-sectional area (ΔTCSA) ratio increased in TRDI with respect to the other treatments as the experiment progressed, reaching differences of 53%. Vegetative growth was clearly sensitive to deficit irrigation with a strong correlation between the increase in the water stress integral obtained by midday stem water potential (Ψstem) and the reduction in TSCA. In contrast, fruit production and quality were not affected by water deficit. As regards the interaction between crop level and water deficit, fruit firmness was the only fruit quality parameter studied that presented significant differences, the highest values corresponding to the fruits from TRDI trees and the lowest crop level. In early nectarine trees, the postharvest period can be considered as a non-critical period for applying RDI strategies but only when the water stress integral applied is of low intensity in May and June (much lower than 9MPa day), in order to limit the decrease in vegetative growth and so not affect the following harvests.
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