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Journal of Materials Chemistry. B Jul 2023Drug delivery in the brain is challenging due to the existence of the blood brain barrier, which prevents most drugs from entering the target site in the brain. Compared... (Review)
Review
Drug delivery in the brain is challenging due to the existence of the blood brain barrier, which prevents most drugs from entering the target site in the brain. Compared to systematic drug administration, localized and site-specific drug delivery in a minimally invasive manner is effective for the treatment of brain disease. However, its implementation relies on advanced technologies and miniaturized implants/devices for controllable drug delivery. Recent research endeavors have provided a broad range of creative neural implants and platforms for this purpose. In this review, we provide an overview of recent advances in miniaturized neural implants for precise, controllable and minimally invasive drug delivery in the brain. This review will focus on neural implants with proven functionalities by discussing the technologies and materials used to fabricate these miniaturized multi-functional drug delivery implants with either externally connected pumps or integrated microfluidic pumps. The vibrancy of engineering technologies and emerging materials associated with these implants and their significance to targeted and minimally invasive drug delivery for brain disease treatment will motivate continued advance and growth of this area of research.
Topics: Humans; Drug Delivery Systems; Brain; Blood-Brain Barrier; Brain Diseases
PubMed: 37310392
DOI: 10.1039/d3tb00728f -
Molecules (Basel, Switzerland) Aug 2023The increased application of drugs during the COVID-19 pandemic has resulted in their increased concentration in wastewater. Conventional wastewater treatment plants do...
The increased application of drugs during the COVID-19 pandemic has resulted in their increased concentration in wastewater. Conventional wastewater treatment plants do not remove such pollutants effectively. Adsorption is a cheap, effective, and environmentally friendly method that can accomplish this. On the other hand, maintaining organic waste is required. Thus, in this study, plant waste-derived pelletized biochar obtained from different feedstock and pyrolyzed at 600 °C was applied for the adsorption of nitazoxanide, an antiparasitic drug used for the treatment of SARS-CoV-2. The adsorption was fast and enables one to remove the drug in one hour. The highest adsorption capacity was noted for biochar obtained from biogas production (14 mg/g). The process of NTZ adsorption was governed by chemisorption (k = 0.2371 g/mg min). The presence of inorganic ions had a detrimental effect on adsorption (Cl, NO in 20-30%) and carbonates were the most effective in hindering the process (60%). The environmentally relevant concentration of DOM (10 mg/L) did not affect the process. The model studies were supported by the results with a real wastewater effluent (15% reduction). Depending on the applied feedstock, various models described nitazoxanide adsorption onto tested biochars. In summary, the application of carbonaceous adsorbents in the pelletized form is effective in nitazoxanide adsorption.
Topics: Humans; Wastewater; Adsorption; Pandemics; COVID-19; SARS-CoV-2; Charcoal; Water Pollutants, Chemical; Kinetics
PubMed: 37570889
DOI: 10.3390/molecules28155919 -
Osteoarthritis and Cartilage Dec 2023To investigate the efficacy of basic fibroblast growth factor (bFGF) in promoting meniscus regeneration by cultivating synovial mesenchymal stem cells (SMSCs) and to...
OBJECTIVE
To investigate the efficacy of basic fibroblast growth factor (bFGF) in promoting meniscus regeneration by cultivating synovial mesenchymal stem cells (SMSCs) and to validate the underlying mechanisms.
METHODS
Human SMSCs were collected from patients with osteoarthritis. Eight-week-old nude rats underwent hemi-meniscectomy, and SMSCs in pellet form, either with or without bFGF (1.0 × 10 cells per pellet), were implanted at the site of meniscus defects. Rats were divided into the control (no transplantation), FGF (-) (pellet without bFGF), and FGF (+) (pellet with bFGF) groups. Different examinations, including assessment of the regenerated meniscus area, histological scoring of the regenerated meniscus and cartilage, meniscus indentation test, and immunohistochemistry analysis, were performed at 4 and 8 weeks after surgery.
RESULTS
Transplanted SMSCs adhered to the regenerative meniscus. Compared with the control group, the FGF (+) group had larger regenerated meniscus areas, superior histological scores of the meniscus and cartilage, and better meniscus mechanical properties. RNA sequencing of SMSCs revealed that the gene expression of chemokines that bind to CXCR2 was upregulated by bFGF. Furthermore, conditioned medium derived from SMSCs cultivated with bFGF exhibited enhanced cell migration, proliferation, and chondrogenic differentiation, which were specifically inhibited by CXCR2 or CXCL6 inhibitors.
CONCLUSION
SMSCs cultured with bFGF promoted the expression of CXCL6. This mechanism may enhance cell migration, proliferation, and chondrogenic differentiation, thereby resulting in superior meniscus regeneration and cartilage preservation.
Topics: Humans; Rats; Animals; Fibroblast Growth Factor 2; Synovial Membrane; Mesenchymal Stem Cells; Meniscus; Regeneration; Cell Differentiation; Cells, Cultured; Mesenchymal Stem Cell Transplantation; Chemokine CXCL6
PubMed: 37562758
DOI: 10.1016/j.joca.2023.07.010 -
Journal of Fungi (Basel, Switzerland) Nov 2023Filamentous fungi are well-known for their ability to form mycelial pellets during submerged cultures, a characteristic that has been extensively studied and applied....
Filamentous fungi are well-known for their ability to form mycelial pellets during submerged cultures, a characteristic that has been extensively studied and applied. However, , a filamentous saprophytic fungus with a rich history of medicinal and culinary applications, has not been widely documented for pellet formation. This study aimed to investigate the factors influencing pellet formation in and their impact on citrinin production, a key secondary metabolite. Through systematic exploration, we identified pH and inoculum size as critical factors governing pellet formation. exhibited optimal pellet growth within the acidic pH range from 5 to 6, resulting in smaller, more homogeneous pellets with lower citrinin content. Additionally, we found that inoculum size played a vital role, with lower spore concentrations favoring the formation of small, uniformly distributed pellets. The choice of carbon and nitrogen sources also influenced pellet stability, with glucose, peptone, and fishmeal supporting stable pellet formation. Notably, citrinin content was closely linked to pellet diameter, with larger pellets exhibiting higher citrinin levels. Our findings shed light on optimizing pellet formation for enhanced citrinin production and provide valuable insights into the cultivation of this fungus for various industrial applications. Further research is warranted to elucidate the molecular mechanisms underlying these observations.
PubMed: 37998925
DOI: 10.3390/jof9111120 -
Bio-protocol Aug 2023Ribosome footprint profiling has demonstrated that ribosomes can be slowed or stalled on select mRNAs, often due to the presence of rare codons, stalling motifs, or via...
Ribosome footprint profiling has demonstrated that ribosomes can be slowed or stalled on select mRNAs, often due to the presence of rare codons, stalling motifs, or via a ribosome-binding protein (e.g., FMRP). Stalled ribosomes can act as physical roadblocks for trailing ribosomes and ultimately can cause ribosome collisions that stimulate no-go mRNA decay. Detecting stalled or slowed ribosomes in cells by ribosome footprint profiling or classic polysome profiling is laborious, technically challenging, and low throughput. Here, we present a protocol to assay for stalled ribosomes on in vitro-transcribed reporter mRNAs using a robust, commercially available mammalian in vitro translation lysate and an optimized low-speed sucrose cushion. In short, we take advantage of the ability of puromycin to incorporate into the nascent polypeptide and cause the ribosome to dissociate from the mRNA during active elongation, as well as the ability to selectively pellet ribosomes through a low-speed sucrose cushion due to their large molecular weight. Stalled ribosomes are not actively elongating and do not incorporate puromycin, allowing the ribosome-bound mRNA to pellet in the low-speed sucrose cushion. RT-qPCR is used to quantify the amount of ribosome-bound reporter mRNA in the pellet. This workflow allows for direct assessment of stalled ribosomes and is fully amendable to insertion of putative stalling motifs in the target mRNA, as well as supplementation with recombinant proteins or small molecule inhibitors that target translation elongation. Key features This protocol is optimized for cap-dependent in vitro translation in the dynamic linear range. Details for generating capped reporter mRNA in one day are provided. Requires as little as one day to complete if starting with in vitro-transcribed mRNA. This protocol requires access to an ultracentrifuge and a real-time PCR system.
PubMed: 37638299
DOI: 10.21769/BioProtoc.4744 -
BMC Genomics Dec 2023Transcriptome studies disentangle functional mechanisms of gene expression regulation and may elucidate the underlying biology of disease processes. However, the types...
Transcriptome studies disentangle functional mechanisms of gene expression regulation and may elucidate the underlying biology of disease processes. However, the types of tissues currently collected typically assay a single post-mortem timepoint or are limited to investigating cell types found in blood. Noninvasive tissues may improve disease-relevant discovery by enabling more complex longitudinal study designs, by capturing different and potentially more applicable cell types, and by increasing sample sizes due to reduced collection costs and possible higher enrollment from vulnerable populations. Here, we develop methods for sampling noninvasive biospecimens, investigate their performance across commercial and in-house library preparations, characterize their biology, and assess the feasibility of using noninvasive tissues in a multitude of transcriptomic applications. We collected buccal swabs, hair follicles, saliva, and urine cell pellets from 19 individuals over three to four timepoints, for a total of 300 unique biological samples, which we then prepared with replicates across three library preparations, for a final tally of 472 transcriptomes. Of the four tissues we studied, we found hair follicles and urine cell pellets to be most promising due to the consistency of sample quality, the cell types and expression profiles we observed, and their performance in disease-relevant applications. This is the first study to thoroughly delineate biological and technical features of noninvasive samples and demonstrate their use in a wide array of transcriptomic and clinical analyses. We anticipate future use of these biospecimens will facilitate discovery and development of clinical applications.
Topics: Humans; Transcriptome; Longitudinal Studies; Gene Expression Profiling; Gene Expression Regulation; Saliva
PubMed: 38114913
DOI: 10.1186/s12864-023-09875-4 -
BioRxiv : the Preprint Server For... Feb 2024Coordinated multi-joint limb and digit movements - "manual dexterity" - underlie both specialized skills (e.g., playing the piano) and more mundane tasks (e.g., tying...
Coordinated multi-joint limb and digit movements - "manual dexterity" - underlie both specialized skills (e.g., playing the piano) and more mundane tasks (e.g., tying shoelaces). Impairments in dexterous skill cause significant disability, as occurs with motor cortical injury, Parkinson's Disease, and a range of other pathologies. Clinical observations, as well as basic investigations, suggest that cortico-striatal circuits play a critical role in learning and performing dexterous skills. Furthermore, dopaminergic signaling in these regions is implicated in synaptic plasticity and motor learning. Nonetheless, the role of striatal dopamine signaling in skilled motor learning remains poorly understood. Here, we use fiber photometry paired with a genetically encoded dopamine sensor to investigate striatal dopamine release as mice learn and perform a skilled reaching task. Dopamine rapidly increases during a skilled reach and peaks near pellet consumption. In dorsolateral striatum, dopamine dynamics are faster than in dorsomedial and ventral striatum. Across training, as reaching performance improves, dopamine signaling shifts from pellet consumption to cues that predict pellet availability, particularly in medial and ventral areas of striatum. Furthermore, performance prediction errors are present across the striatum, with reduced dopamine release after an unsuccessful reach. These findings show that dopamine dynamics during skilled motor behaviors change with learning and are differentially regulated across striatal subregions.
PubMed: 38370850
DOI: 10.1101/2024.02.06.579240 -
Journal of Forensic Sciences Mar 2024When reconstructing a shooting incident with a shotgun, the muzzle-to-target distance can be determined by relating the size of a dispersion pattern found on a crime...
When reconstructing a shooting incident with a shotgun, the muzzle-to-target distance can be determined by relating the size of a dispersion pattern found on a crime scene to that of test shots. Ideally, the test shots are performed with the weapon and ammunition that were used in the incident. But sometimes examiners will have to resort to alternatives, such as using cartridges of the same brand and type but with another pellet size. For this reason, the relationship between pellet size and shotgun dispersion patterns was studied with both lead and steel shotgun pellets. Cartridges were loaded with identical cartridge cases, powder charges, and wads but with different pellet sizes, below size B. The cartridges were fired, and the dispersion patterns at 5 m in front of the muzzle were measured and compared. The results provide strong support for the proposition that shotgun dispersion patterns with both lead and steel shot increase with decreasing pellet size if all other relevant parameters are kept equal. The results also provide an indicative measure of the magnitude of the effect. Pattern sizes were approximately 1.7 times larger with #9 than with #0 lead shot and 1.4 times larger with #9 than with #1 steel shot. The differences between consecutive shot sizes were generally smaller. This means that cartridges of equal brand and type but with the next nearest shot number can be used for a muzzle-to-target distance determination, keeping the information of the current study in mind in the final interpretation of the results.
PubMed: 38037238
DOI: 10.1111/1556-4029.15427 -
Neurogastroenterology and Motility Aug 2023Gastrointestinal motility measurements in mice are currently performed under suboptimal conditions, as these nocturnal animals are measured during light conditions. In...
BACKGROUND
Gastrointestinal motility measurements in mice are currently performed under suboptimal conditions, as these nocturnal animals are measured during light conditions. In addition, other stressors, like individual housing, placement in a new cage during observation, and lack of bedding and cage enrichment cause animal discomfort and might contribute to higher variability. Here we aimed to develop a refined method of the widely-used whole-gut transit assay.
METHODS
Wildtype mice (N = 24) were subjected to the standard or refined whole-gut transit assay, either with or without a standardized slowing in gastrointestinal motility induced by loperamide. The standard assay consisted of a gavage with carmine red, observation during the light period and individual housing in a new cage without cage enrichment. For the refined whole-gut transit assay, mice were gavaged with UV-fluorescent DETEX®, observed during the dark period, while pairwise housed in their home cage with cage enrichment. Time until excretion of the first colored fecal pellet was assessed, and pellets were collected to assess number, weight, and water content.
KEY RESULTS
The DETEX®-containing pellets were UV-detectable, allowing to measure the mice in their active period in the dark. The refined method caused less variation (20.8% and 16.0%) compared to the standard method (29.0% and 21.7%). Fecal pellet number, weight, and water content was significantly different between the standard and refined method.
CONCLUSIONS & INFERENCES
This refined whole-gut transit assay provides a reliable approach to measure whole-gut transit time in mice in a more physiological context, with reduced variability compared to the standard method.
Topics: Mice; Animals; Gastrointestinal Motility; Feces; Loperamide; Water; Gastrointestinal Transit
PubMed: 37010851
DOI: 10.1111/nmo.14586 -
BMC Complementary Medicine and Therapies May 2024For elderly people with chronic lower back pain who need long-term management, there is a need for a nursing intervention study that is effective, is easy to perform,... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
For elderly people with chronic lower back pain who need long-term management, there is a need for a nursing intervention study that is effective, is easy to perform, and applies complementary and alternative therapies to manage pain without repulsion. Hand pressure therapy is a treatment indigenous to Korea used to reduce pain and improve functions of daily life by applying acupuncture, pressure sticks, and moxibustion to parts of the hand as they relate to parts of the body. This research is to identify the effects of pellet pressed on the hand on pain and the daily lives of elders with chronic lower back pain (CLBP).
METHODS
The hand pressed-pellet intervention period was six weeks long. Twenty-seven patients in the intervention group and twenty-four patients in the placebo control group were recruited from elderly over sixty-five who used welfare centers. In the intervention group, hand pressed-pellet therapy was conducted in eleven acupressure response zones related to CLBP, and the placebo control group was provided with similar therapy and zones, but unrelated to CLBP. The research tool measured the intensity of CLBP using the Visual Analogue Scale (VAS), the Korean Owestry Disability Index (K-ODI), which are subjective indicators, and the Compact Digital Algometer, which is an objective indicator.
RESULT
The pain intensity (VAS) measured after six weeks of hand pressed-pellet therapy showed significant difference between the two groups compared to their pain before the experiment (F = 60.522, p < .001). There was a significant difference between the two groups in the pain pressure threshold using pressure statistics (F = 8.940, p < .001), and in CLBP dysfunction evaluation index (K-ODI) after applying pressed pellet to the hand (Z = - 3.540, p < .001).
CONCLUSION
Subjective indicators were measured to verify the effect of hand pressed-pellet therapy on CLBP, and the result confirmed that the hand pressed-pellet therapy was effective in alleviating CLBP.
TRIAL REGISTRATION
The study was registered retrospectively with reference number KCT0008024 on 23/12/2022.
Topics: Humans; Aged; Male; Female; Low Back Pain; Hand; Chronic Pain; Activities of Daily Living; Republic of Korea; Acupressure; Pain Measurement; Aged, 80 and over
PubMed: 38702676
DOI: 10.1186/s12906-024-04481-7