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1.
Materials (Basel) ; 17(12)2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38930355

ABSTRACT

The application prospects of composite sponges with antibacterial and drug-carrying functions in the field of medical tissue engineering are extensive. A solution of cassava silk fibroin (CSF) was prepared with Ca(NO3)2 as a solvent, which was then combined with chitosan (CS) to create a sponge-porous material by freeze-drying. The CSF-CS composite sponge with a mesh structure was successfully fabricated through hydrogen bonding. Scanning electron microscopy (SEM), Fourier transform infrared absorption (FTIR) and X-ray diffraction (XRD) were employed to investigate the appearance and structure of the cassava silk's fibroin materials, specifically examining the impact of different mass percentages of CS on the sponge's structure. The swelling rate and mechanical properties of the CSF-CS sponge were analyzed, along with its antibacterial properties. Furthermore, by incorporating ibuprofen as a model drug into these loaded sponges, their potential efficacy as efficient drug delivery systems was demonstrated. The results indicate that the CSF-CS sponge possesses a three-dimensional porous structure with over 70% porosity and an expansion rate exceeding 400% while also exhibiting good resistance against pressure. Moreover, it exhibits excellent drug-carrying ability and exerts significant bacteriostatic effects on Escherichia coli. Overall, these findings support considering the CSF-CS composite sponge as a viable candidate for use in drug delivery systems or wound dressings.

2.
Sci Total Environ ; 940: 173349, 2024 Aug 25.
Article in English | MEDLINE | ID: mdl-38772487

ABSTRACT

The high toxicity and persistence of polychlorinated biphenyls (PCBs) in the environment require effective remediation of PCBs-contaminated soil. This study used polylactic acid (PLA) and polyethylene glycol 4000 (PEG-4000) to modify zero-valent iron nanoparticles (nZVI) and conducted characterization analysis. It was found that when the addition amount of PLA was 2 %, the dispersion of modified nZVI was better. The initial pH and water to soil ratio were subjected to single factor experiments and fitted using RSM response surface methodology. The optimal reaction conditions were obtained as follows: the addition amount was 84 g·kg-1, the initial pH was 5.41, and the optimal removal rate was 74 % when the ratio of water to soil was 1.8:1. PLA and PEG-4000 were biodegradable substances that played crucial roles in enhancing the effectiveness of nZVI for PCBs-contaminated soil. By encapsulating nZVI with PLA, we significantly reduced its oxidation when exposed to air. Additionally, the inclusion of PEG-4000 helped prevent the particles from clumping together. The synergistic effect of them increased the effective reaction of nZVI and PCBs and ultimately leading to more efficient remediation. This study offered a new pathway for the efficient green remediation of PCBs-contaminated soil.

3.
Brain Sci ; 14(5)2024 May 15.
Article in English | MEDLINE | ID: mdl-38790476

ABSTRACT

In this study, we investigated the feasibility of using electroencephalogram (EEG) signals to differentiate between four distinct subject-driven cognitive states: resting state, narrative memory, music, and subtraction tasks. EEG data were collected from seven healthy male participants while performing these cognitive tasks, and the raw EEG signals were transformed into time-frequency maps using continuous wavelet transform. Based on these time-frequency maps, we developed a convolutional neural network model (TF-CNN-CFA) with a channel and frequency attention mechanism to automatically distinguish between these cognitive states. The experimental results demonstrated that the model achieved an average classification accuracy of 76.14% in identifying these four cognitive states, significantly outperforming traditional EEG signal processing methods and other classical image classification algorithms. Furthermore, we investigated the impact of varying lengths of EEG signals on classification performance and found that TF-CNN-CFA demonstrates consistent performance across different window lengths, indicating its strong generalization capability. This study validates the ability of EEG to differentiate higher cognitive states, which could potentially offer a novel BCI paradigm.

4.
J Nanobiotechnology ; 22(1): 203, 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38659001

ABSTRACT

BACKGROUND: Biogeochemical processing of metals including the fabrication of novel nanomaterials from metal contaminated waste streams by microbial cells is an area of intense interest in the environmental sciences. RESULTS: Here we focus on the fate of Ce during the microbial reduction of a suite of Ce-bearing ferrihydrites with between 0.2 and 4.2 mol% Ce. Cerium K-edge X-ray absorption near edge structure (XANES) analyses showed that trivalent and tetravalent cerium co-existed, with a higher proportion of tetravalent cerium observed with increasing Ce-bearing of the ferrihydrite. The subsurface metal-reducing bacterium Geobacter sulfurreducens was used to bioreduce Ce-bearing ferrihydrite, and with 0.2 mol% and 0.5 mol% Ce, an Fe(II)-bearing mineral, magnetite (Fe(II)(III)2O4), formed alongside a small amount of goethite (FeOOH). At higher Ce-doping (1.4 mol% and 4.2 mol%) Fe(III) bioreduction was inhibited and goethite dominated the final products. During microbial Fe(III) reduction Ce was not released to solution, suggesting Ce remained associated with the Fe minerals during redox cycling, even at high Ce loadings. In addition, Fe L2,3 X-ray magnetic circular dichroism (XMCD) analyses suggested that Ce partially incorporated into the Fe(III) crystallographic sites in the magnetite. The use of Ce-bearing biomagnetite prepared in this study was tested for hydrogen fuel cell catalyst applications. Platinum/carbon black electrodes were fabricated, containing 10% biomagnetite with 0.2 mol% Ce in the catalyst. The addition of bioreduced Ce-magnetite improved the electrode durability when compared to a normal Pt/CB catalyst. CONCLUSION: Different concentrations of Ce can inhibit the bioreduction of Fe(III) minerals, resulting in the formation of different bioreduction products. Bioprocessing of Fe-minerals to form Ce-containing magnetite (potentially from waste sources) offers a sustainable route to the production of fuel cell catalysts with improved performance.


Subject(s)
Cerium , Ferrosoferric Oxide , Geobacter , Platinum , Cerium/chemistry , Cerium/metabolism , Geobacter/metabolism , Catalysis , Ferrosoferric Oxide/chemistry , Platinum/chemistry , Oxidation-Reduction , Ferric Compounds/chemistry , Ferric Compounds/metabolism
5.
Oncol Res ; 32(5): 933-941, 2024.
Article in English | MEDLINE | ID: mdl-38686051

ABSTRACT

MicroRNA (miR)-200b-3p has been associated with many tumors, but its involvement in pituitary adenoma is unclear. This study investigated the molecular mechanism underlying miR-200b-3p regulation in pituitary adenomas to provide a theoretical basis for treatment. Bioinformatics was used to analyze pituitary adenoma-related genes and screen new targets related to RECK and miRNA. As well, the relationship between miR-200b-3p and RECK protein was verified using a double-luciferase reporter gene assay. The expression of miR-200b-3p in clinical samples was analyzed by in situ hybridization. Transfection of the miR-200b-3p inhibitor and small interfering-RECK (si-RECK) was verified by qPCR. GH3 cell viability and proliferation were detected using CCK8 and EdU assays. Apoptosis was detected by flow cytometry and western blotting. Wound healing and Transwell assays were used to detect cell migration and invasion. The effects of miR-200b-3p and RECK on GH3 cells were verified using salvage experiments. miR-200b-3p was highly expressed in pituitary tumor tissue. Inhibitors of miR-200b-3p inhibited cell proliferation promoted cell apoptosis, inhibited invasion and migration, and inhibited the expression of matrix metalloproteinases. Interestingly, miR-200b-3p negatively regulated RECK. The expression of RECK in pituitary adenoma tissues was lower than that in neighboring tissues. Si-RECK rescued the function of miR-200b-3p inhibitors in the above cellular behaviors, and miR-200b-3p accelerated the development of pituitary adenoma by negatively regulating RECK expression. In summary, this study investigated the molecular mechanism by which miR-200b-3p regulates the progression of pituitary adenoma through the negative regulation of RECK. The findings provide a new target for the treatment of pituitary adenoma.


Subject(s)
Adenoma , Apoptosis , GPI-Linked Proteins , Gene Expression Regulation, Neoplastic , MicroRNAs , Pituitary Neoplasms , Animals , Female , Humans , Male , Rats , Adenoma/genetics , Adenoma/pathology , Adenoma/metabolism , Apoptosis/genetics , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Disease Progression , GPI-Linked Proteins/genetics , GPI-Linked Proteins/metabolism , MicroRNAs/genetics , Pituitary Neoplasms/genetics , Pituitary Neoplasms/pathology , Pituitary Neoplasms/metabolism
6.
Mol Immunol ; 170: 88-98, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38643689

ABSTRACT

The pathogenesis of neuropathic pain (NP) is complex, and there are various pathological processes. Previous studies have suggested that lncRNA PCAT19 is abnormally expressed in NP conduction and affects the occurrence and development of pain. The aim of this study is to analyze the role and mechanism of PCAT19 in NP induced by chronic compressive nerve injury (CCI) in mice. In this study, C57BL/6 mice were applied to establish the CCI model. sh-PCAT19 was intrathecally injected once a day for 5 consecutive days from the second day after surgery. We discovered that PCat19 level was gradually up-regulated with the passage of modeling time. Downregulation of Iba-1-positive expression, M1/M2 ratio of microglia, and pro-inflammatory factors in the spinal cords of CCI-mice after PCat19 knock-downed was observed. Mechanically, the expression of miR-378a-3p was negatively correlated with KDM3A and PCat19. Deletion of KDM3A prevented H3K9me2 demethylation of BDNF promoter and suppressed BDNF expression. Further, KDM3A promotes CCI-induced neuroinflammation and microglia activation by mediating Brain-derived neurotrophic factor (BDNF) demethylation. Together, the results suggest that PCat19 may be involved in the development of NP and that PCat19 shRNA injection can attenuate microglia-induced neuroinflammation by blocking KDM3A-mediated demethylation of BDNF and BDNF release.


Subject(s)
Brain-Derived Neurotrophic Factor , Mice, Inbred C57BL , MicroRNAs , Microglia , Neuralgia , RNA, Long Noncoding , Animals , Neuralgia/genetics , Neuralgia/metabolism , Microglia/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , RNA, Long Noncoding/genetics , Brain-Derived Neurotrophic Factor/metabolism , Brain-Derived Neurotrophic Factor/genetics , Male , Mice , Rats , Jumonji Domain-Containing Histone Demethylases/genetics , Jumonji Domain-Containing Histone Demethylases/metabolism , Demethylation , Rats, Sprague-Dawley , Disease Models, Animal , Chronic Pain/genetics , Chronic Pain/metabolism , RNA, Competitive Endogenous
7.
J Biomed Res ; 38(2): 175-188, 2024 Mar 05.
Article in English | MEDLINE | ID: mdl-38438134

ABSTRACT

Deterministic compartment models (CMs) and stochastic models, including stochastic CMs and agent-based models, are widely utilized in epidemic modeling. However, the relationship between CMs and their corresponding stochastic models is not well understood. The present study aimed to address this gap by conducting a comparative study using the susceptible, exposed, infectious, and recovered (SEIR) model and its extended CMs from the coronavirus disease 2019 modeling literature. We demonstrated the equivalence of the numerical solution of CMs using the Euler scheme and their stochastic counterparts through theoretical analysis and simulations. Based on this equivalence, we proposed an efficient model calibration method that could replicate the exact solution of CMs in the corresponding stochastic models through parameter adjustment. The advancement in calibration techniques enhanced the accuracy of stochastic modeling in capturing the dynamics of epidemics. However, it should be noted that discrete-time stochastic models cannot perfectly reproduce the exact solution of continuous-time CMs. Additionally, we proposed a new stochastic compartment and agent mixed model as an alternative to agent-based models for large-scale population simulations with a limited number of agents. This model offered a balance between computational efficiency and accuracy. The results of this research contributed to the comparison and unification of deterministic CMs and stochastic models in epidemic modeling. Furthermore, the results had implications for the development of hybrid models that integrated the strengths of both frameworks. Overall, the present study has provided valuable epidemic modeling techniques and their practical applications for understanding and controlling the spread of infectious diseases.

8.
Heliyon ; 10(5): e27518, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38463836

ABSTRACT

The goal of "carbon peak, carbon neutral" and the increasing expansion of new energy have helped to advance the development of energy storage. However, since the operating cost of energy storage is high, carbon emission trading and power market trading have emerged, effectively improving the efficiency. In this paper, a trading strategy and bidding framework of energy storage participation in the day-ahead joint market are studied. A market bidding model has been established in a framework based on the Stackelberg game. Finally, the "Day-Ahead and Intra-Day and Carbon Emission Trading (CET)" market clearing model has been constructed. It has been simplified to solve the equivalent mixed-integer linear programming (MILP) problem with equilibrium constraints through the use of the Karush-Kuhn-Tucker (KKT) optimality criterion and duality principle. The proposed model is validated through improved examples to obtain thermal unit output cuts of up to 32.2% during load trough periods, and up to 16.75% increase in clearing prices during peak load periods. The storage life is extended and the storage output variation is minimized.

10.
PeerJ ; 12: e16848, 2024.
Article in English | MEDLINE | ID: mdl-38371374

ABSTRACT

Background: The Index of Consciousness (IoC) is a new monitoring index of anesthesia depth reflecting the state of consciousness of the brain independently developed by China. The research on monitoring the depth of anesthesia mainly focuses on propofol, and bispectral index (BIS) is a sensitive and accurate objective index to evaluate the state of consciousness at home and abroad. This study mainly analyzed the effect of IoC on monitoring the depth of sevoflurane anesthesia and the consistency and accuracy with BIS when monitoring sevoflurane maintenance anesthesia. Objective: To investigate the monitoring value of the Index of Consciousness (IoC) for the depth of sevoflurane anesthesia in laparoscopic surgery. Methods: The study population consisted of 108 patients who experienced elective whole-body anesthesia procedures within the timeframe of April 2020 to June 2023 at our hospital. Throughout the anesthesia process, which encompassed induction and maintenance using inhaled sevoflurane, all patients were diligently monitored for both the Bispectral Index (BIS) and the Index of Consciousness (IoC). We conducted an analysis to assess the correlation between IoC and BIS throughout the anesthesia induction process and from the maintenance phase to the regaining of consciousness. To evaluate the predictive accuracy of IoC and BIS for the onset of unconsciousness during induction and the return of consciousness during emergence, we employed receiver operating characteristic (ROC) curve analysis. Results: The mean difference between BIS and IoC, spanning from the pre-anesthesia induction phase to the completion of propofol induction, was 1.3 (95% Limits of Agreement [-53.4 to 56.0]). Similarly, during the interval from the initiation of sevoflurane inhalation to the point of consciousness restoration, the average difference between BIS and IoC was 0.3 (95% LOA [-10.8 to 11.4]). No statistically significant disparities were observed in the data acquired from the two measurement methodologies during both the anesthesia induction process and the journey from maintenance to the regaining of consciousness (P > 0.05). The outcomes of the ROC curve analysis disclosed that the areas under the curve (AUC) for prognosticating the occurrence of loss of consciousness were 0.967 (95% CI [0.935-0.999]) for BIS and 0.959 (95% CI [0.924-0.993]) for IoC, with optimal threshold values set at 81 (sensitivity: 88.10%, specificity: 92.16%) and 77 (sensitivity: 79.55%, specificity: 95.45%) correspondingly. For the prediction of recovery of consciousness, the AUCs were 0.995 (95% CI [0.987-1.000]) for BIS and 0.963 (95% CI [0.916-1.000]) for IoC, each associated with optimal cutoff values of 76 (sensitivity: 92.86%, specificity: 100.00%) and 72 (sensitivity: 86.36%, specificity: 100.00%) respectively. Conclusion: The monitoring of sevoflurane anesthesia maintenance using IoC demonstrates a level of comparability to BIS, and its alignment with BIS during the maintenance phase of sevoflurane anesthesia is robust. IoC displays promising potential for effectively monitoring the depth of anesthesia.


Subject(s)
Anesthetics, Inhalation , Laparoscopy , Methyl Ethers , Propofol , Humans , Sevoflurane , Propofol/pharmacology , Consciousness , Anesthetics, Inhalation/pharmacology , Methyl Ethers/pharmacology , Monitoring, Intraoperative/methods , Anesthesia, General/methods
11.
Sensors (Basel) ; 24(2)2024 Jan 19.
Article in English | MEDLINE | ID: mdl-38276337

ABSTRACT

SLAM (Simultaneous Localization and Mapping) based on 3D LiDAR (Laser Detection and Ranging) is an expanding field of research with numerous applications in the areas of autonomous driving, mobile robotics, and UAVs (Unmanned Aerial Vehicles). However, in most real-world scenarios, dynamic objects can negatively impact the accuracy and robustness of SLAM. In recent years, the challenge of achieving optimal SLAM performance in dynamic environments has led to the emergence of various research efforts, but there has been relatively little relevant review. This work delves into the development process and current state of SLAM based on 3D LiDAR in dynamic environments. After analyzing the necessity and importance of filtering dynamic objects in SLAM, this paper is developed from two dimensions. At the solution-oriented level, mainstream methods of filtering dynamic targets in 3D point cloud are introduced in detail, such as the ray-tracing-based approach, the visibility-based approach, the segmentation-based approach, and others. Then, at the problem-oriented level, this paper classifies dynamic objects and summarizes the corresponding processing strategies for different categories in the SLAM framework, such as online real-time filtering, post-processing after the mapping, and Long-term SLAM. Finally, the development trends and research directions of dynamic object filtering in SLAM based on 3D LiDAR are discussed and predicted.

12.
Int J Pharm ; 652: 123809, 2024 Mar 05.
Article in English | MEDLINE | ID: mdl-38224760

ABSTRACT

Alzheimer's disease (AD) is characterized by a gradual decline in cognitive function and memory impairment, significantly impacting the daily lives of patients. Rivastigmine (RHT), a cholinesterase inhibitor, is used to treat mild to moderate AD via oral administration. However, oral administration is associated with slow absorption rate and severe systemic side effects. RHT nasal spray (RHT-ns), as a nose-to-brain delivery system, is more promising for AD management due to its efficient brain delivery and reduced peripheral exposure. This study constructed RHT-ns for enhancing AD treatment efficacy, and meanwhile the correlation between drug olfactory deposition and drug entering into the brain was explored. A 3D-printed nasal cast was employed to quantify the drug olfactory deposition. Brain delivery of RHT-ns was quantified using fluorescence tracking and Desorption Electrospray Ionization Mass Spectrometry (DESI-MS) analysis, which showed a good correlation to the olfactory deposition. F2 (containing 1% (w/v) viscosity modifier Avicel® RC-591) with high olfactory deposition and drug brain delivery was further investigated for pharmacodynamics study. F2 exhibited superiority in AD treatment over the commercially available oral formulation. In summary, the present study showed the successful development of RHT-ns with improved olfactory deposition and enhanced brain delivery. It might provide new insight into the design and development of nose-to-brain systems for the treatment of AD.


Subject(s)
Alzheimer Disease , Humans , Rivastigmine/chemistry , Rivastigmine/therapeutic use , Alzheimer Disease/drug therapy , Nasal Sprays , Administration, Intranasal , Brain , Cholinesterase Inhibitors
13.
J Agric Food Chem ; 72(1): 259-273, 2024 Jan 10.
Article in English | MEDLINE | ID: mdl-38064688

ABSTRACT

This study aims to explore the effects of Astragaloside IV (AS-IV) on abnormal behaviors, intestinal microbiota, intestinal T-immune balance, and fecal metabolism of a model of depression in rats. Herein, we integrally applied 16S rRNA sequencing, molecular biological techniques, and 1H NMR-based fecal metabolomics to demonstrate the antidepression activity of AS-IV. The results suggested that AS-IV regulated the depression-like behaviors of rats, which are presented by an increase of body weight, upregulation of sucrose preference rates, and a decrease of immobility time. Additionally, AS-IV increased the abundances of beneficial bacteria (Lactobacillus and Oscillospira) in a model of depression in rats. Moreover, AS-IV regulated significantly the imbalance of Th17/Treg cells, and the abnormal contents of both anti-inflammatory factors and pro-inflammatory factors. Besides, fecal metabolomics showed that AS-IV improved the abnormal levels of short-chain fatty acids and amino acids. Collectively, our research supplemented new data, supporting the potential of AS-IV as an effective diet or diet composition to improve depression-like behaviors, dysfunctions of microbiota, imbalance of T immune, and the abnormality of fecal metabolome. However, the causality of the other actions was not proven because of the experimental design and the methodology used. The current findings suggest that AS-IV could function as a promising diet or diet composition to alleviate depressed symptoms.


Subject(s)
Gastrointestinal Microbiome , Rats , Animals , Depression/drug therapy , Depression/genetics , Depression/microbiology , RNA, Ribosomal, 16S/genetics , Metabolome
14.
Sci Total Environ ; 912: 169140, 2024 Feb 20.
Article in English | MEDLINE | ID: mdl-38070561

ABSTRACT

Ocular surface diseases are common in the plateau city, Kunming China, the continued daily exposure to heavy metals in dust may be an important inducement. In this study, the 150 road dust samples from five functional areas in Kunming were collected. The concentrations, distribution, possible sources, and bioaccessibility of heavy metals were analyzed. The adverse effects of dust extracts on human corneal epithelial cells and the underlying mechanisms were also assessed. The concentrations (mg·kg-1) of As (19.1), Cd (2.67), Cr (90.5), Cu (123), Pb (78.4), and Zn (389) in road dust were higher than the soil background, with commercial and residential areas showing the highest pollution. Their bioaccessibility in artificial tears was As (6.59 %) > Cu (5.11 %) > Ni (1.47 %) > Cr (1.17 %) > Mn (0.84 %) > Cd (0.76 %) > Zn (0.50 %) > Pb (0.31 %). The two main sources of heavy metals included tire and mechanical abrasion (24.5 %) and traffic exhaust (21.6 %). All dust extracts induced cytotoxicity, evidenced by stronger inhibition of cell viability, higher production of ROS, and altered mRNA expression of antioxidant enzymes and cell cycle-related genes, with commercial- areas-2 (CA2)-dust extract showing the greatest oxidative damage and cell cycle arrest. Our data may provide new evidence that dust exposure in high geological background cities could trigger human cornea damage.


Subject(s)
Dust , Metals, Heavy , Humans , Dust/analysis , Cities , Environmental Monitoring , Cadmium , Lead , Metals, Heavy/toxicity , Metals, Heavy/analysis , China , Risk Assessment
15.
Stress Health ; 40(3): e3357, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38126682

ABSTRACT

The COVID-19 pandemic disrupted life around the globe and negatively impacted mental health (MH), including among military veterans. Building on previous research with U.S. veterans, the present study examined the association between a broad array of pandemic stressors and well-being on MH outcomes. A total of 372 veterans (51.3% women) from all service eras completed measures of posttraumatic stress disorder and depression during early (timepoint 1 [T1]) and peri-pandemic (timepoint 2 [T2]) periods. Pandemic-related stressors and well-being (satisfaction in life domains) were assessed at the peri-pandemic timepoint (T2). Logistic regression analyses were used to investigate associations between stressors and well-being with the likelihood of a probable MH diagnosis at T2 controlling for T1 MH status. More negative physical and MH impacts of the pandemic in addition to fewer positive consequences and lower satisfaction with paid work, finances, health, romantic relationships, and social life were associated with a higher likelihood of a probable T2 MH diagnosis. COVID infection was associated with lower odds of a probable T2 MH diagnosis. There were significant indirect effects, such that physical and MH impacts of the pandemic were associated with T2 MH via well-being. Overall, these findings highlight the role of stress and well-being on MH during a global pandemic. Interventions to address well-being may be important to address veteran MH during other periods of stress. Future research should examine the generalizability of study findings and further investigate factors that contribute to veterans' MH resilience during stressful life experiences.


Subject(s)
COVID-19 , Depression , Stress Disorders, Post-Traumatic , Stress, Psychological , Veterans , Humans , COVID-19/psychology , COVID-19/epidemiology , Female , Male , Veterans/psychology , Veterans/statistics & numerical data , Middle Aged , United States/epidemiology , Adult , Depression/psychology , Depression/epidemiology , Stress Disorders, Post-Traumatic/epidemiology , Stress Disorders, Post-Traumatic/psychology , Stress, Psychological/psychology , Stress, Psychological/epidemiology , Mental Health , Personal Satisfaction , Aged , SARS-CoV-2
17.
J Nanobiotechnology ; 21(1): 473, 2023 Dec 09.
Article in English | MEDLINE | ID: mdl-38066528

ABSTRACT

BACKGROUND: Gene therapy for lung cancer has emerged as a novel tumor-combating strategy for its superior tumor specificity, low systematical toxicity and huge clinical translation potential. Especially, the applications of microRNA shed led on effective tumor ablation by directly interfering with the crucial gene expression, making it one of the most promising gene therapy agents. However, for lung cancer therapy, the microRNA treatment confronted three bottlenecks, the poor tumor tissue penetration effect, the insufficient lung drug accumulation and unsatisfied gene transfection efficiency. To address these issues, an inhalable RGD-TAT dual peptides-modified cationic liposomes loaded with microRNA miR-34a and gap junction (GJ) regulation agent all-trans retinoic acid (ATRA) was proposed, which was further engineered into dry powder inhalers (DPIs). RESULTS: Equipped with a rough particle surface and appropriate aerodynamic size, the proposed RGD-TAT-CLPs/ARTA@miR-34a DPIs were expected to deposit into the deep lung and reach lung tumor lesions guided by targeting peptide RGD. Assisted by cellular transmembrane peptides TAT, the RGD-TAT-CLPs/ARTA@miR-34a was proven to be effectively internalized by cancer cells, enhancing gene transfection efficiency. Then, the GJ between tumor cells was upregulated by ARTA, facilitating the intercellular transport of miR-34a and boosting the gene expression in the deep tumor. CONCLUSION: Overall, the proposed RGD-TAT-CLPs/ARTA@miR-34a DPIs could enhance tumor tissue penetration, elevate lung drug accumulation and boost gene transfection efficiency, breaking the three bottlenecks to enhancing tumor elimination in vitro and in vivo. We believe that the proposed RGD-TAT-CLPs/ARTA@miR-34a DPIs could serve as a promising pulmonary gene delivery platform for multiple lung local disease treatments.


Subject(s)
Lung Neoplasms , MicroRNAs , Humans , Liposomes , Lung Neoplasms/therapy , MicroRNAs/genetics , MicroRNAs/metabolism , Lung/metabolism , Oligopeptides , Gap Junctions/metabolism , Genes, Neoplasm , Cell Line, Tumor
18.
Int J Pharm ; 648: 123580, 2023 Dec 15.
Article in English | MEDLINE | ID: mdl-37944677

ABSTRACT

The supercritical antisolvent-fluidized bed coating process (SAS-FB) shows great potential as a technique to manufacture dry powder inhaler (DPI) that incorporate nanodrugs onto micronized matrix particles, capitalizing on the merits of both nanoparticle and pulmonary delivery. In this study, naringin (NAR), a pharmacologically active flavonoid with low solubility and in vivo degradation issues, was utilized as a model active pharmaceutical ingredient to construct nanomedicine-based DPI through SAS-FB. It is showed that processed NAR exhibited a near-spherical shape and an amorphous structure with an average size of around 130 nm. Notably, SAS-FB products prepared with different fluidized matrices resulted in varying deposition patterns, particularly when mixed with a coarse lactose to enhance the fine particle fraction (FPF) of the formulations. The FPF was positively associated with specific surface area of the SAS-FB products, while the specific surface area was directly related to surface roughness and particle size. In vitro dissolution studies using simulated lung fluid revealed that the NAR nanoparticles coated on the products were released immediately upon contact with solution, with a cumulative dissolution exceeding 90% within the first minute. Importantly, compared to oral raw NAR, the optimized DPI formulation demonstrated superior in vivo plasmatic and pulmonary AUC0→∞ by 51.33-fold and 104.07-fold respectively in a Sprague-Dawley rat model. Overall, SAS- FB technology provides a practical approach to produce nanomedicine DPI product that combine the benefits of nanoparticles with the aerodynamics properties of inhaled microparticles.


Subject(s)
Dry Powder Inhalers , Nanomedicine , Rats , Animals , Dry Powder Inhalers/methods , Rats, Sprague-Dawley , Administration, Inhalation , Lung , Particle Size , Powders
19.
BMC Anesthesiol ; 23(1): 328, 2023 10 02.
Article in English | MEDLINE | ID: mdl-37784027

ABSTRACT

While the mechanism of general anesthesia has been extensively studied, the underlying neural circuitry has yet to be fully understood. The parabrachial nucleus (PBN) plays a crucial role in modulating wakefulness and promoting arousal from general anesthesia. However, the specific role of PBN projections in the process of general anesthesia remains unclear. In this study, we bilaterally injected AAV-associated viruses encoding excitatory or inhibitory optogenetic probes into the PBN and implanted optical fibers in the LH or BF area. After four weeks, we optogenetically activated or inhibited the PBN-LH and PBN-BF pathways under 1.5 vol% isoflurane. We calculated the time it took for anesthesia induction and emergence, simultaneously monitoring changes in the burst-suppression ratio using electroencephalogram recording. Our findings indicate that optogenetic activation of the PBN-LH and PBN-BF projections plays a significant role in promoting both cortical and behavioral emergence from isoflurane inhalation, without significantly affecting the induction time. Conversely, photoinhibition of these pathways prolonged the recovery time, with no notable difference observed during the induction phase.In summary, our results demonstrate that the PBN-LH and PBN-BF pathways are crucial for promoting arousal from isoflurane general anesthesia, but do not have a pronounced impact on the induction phase.


Subject(s)
Anesthetics, Inhalation , Basal Forebrain , Isoflurane , Parabrachial Nucleus , Mice , Animals , Isoflurane/pharmacology , Anesthetics, Inhalation/pharmacology , Hypothalamic Area, Lateral , Optogenetics , Anesthesia, General
20.
Article in English | MEDLINE | ID: mdl-37815755

ABSTRACT

OBJECTIVES: To describe the differences and similarities in perceptions and attitudes regarding COVID-19 vaccination among Black and Latinx Michiganders. METHODS: Utilizing a convergent mixed-methods approach, forty interviews were conducted with 24 Black and 16 Latinx community members between December 2020 and June 2021 across four Michigan counties disproportionately affected by COVID-19. Survey data were collected from a representative sample of 1598 individuals living in Detroit between January and March 2021. RESULTS: Vaccine hesitancy was a more prevalent theme among Black interview participants than Latinx participants. Trust in experts and vaccine access were significantly more influential in the decision to vaccinate for Latinx residents compared to Black residents. Latinx individuals reported greater intention to receive a COVID-19 vaccine compared to Black respondents. Multinomial logit models revealed that 30% of Black participants expressed hesitancy about the COVID-19 vaccine compared to 10% of Latinx respondents. CONCLUSIONS AND IMPLICATIONS: This study provides a deeper understanding of key differences and similarities in vaccine acceptance/hesitancy across race/ethnicity. The findings can enhance health interventions and outcomes by informing the development of culturally responsive practices tailored to specific communities.

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