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1.
Front Med (Lausanne) ; 11: 1387773, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38665293

RESUMO

In this report, a female patient suffering from pigment retention caused by a skin marking pen was elucidated. The patient underwent blepharoplasty 6 months ago and presented with blue-black linear marks at the upper eyelid incision 2 weeks after surgery. Under dermoscopy, scattered pigments were observed to accumulate in the epidermis of the upper eyelid. The patient was diagnosed with iatrogenic tattoo by a surgical marking pen. We chose surgical excision of the skin with the pigmentation. Previous studies have established that the risk of bacterial contamination, contact dermatitis, and allergies may increase with the surgical marking pens, while pigment retention has not yet been mentioned yet. Here, we present a case with a pigment retention in the incision. The selection of the surgical labelling methods and the management of the pigmentation were also addressed. According to our clinical findings, the risk of pigment retention by marking pens needs to be mentioned in the patient's informed consent. Therefore, the practitioner should ensure that the ink is cleaned by the end of each invasive procedure.

2.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 42(2): 262-267, 2024 Apr 01.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-38597087

RESUMO

Robotic surgery is known as the "third technological revolution" in the field of surgery, and is an important milestone in the development of modern surgery. However, our country's innovative surgical robot industry is still in its early stages, and it is only being utilized in certain surgical fields. To explore the effectiveness of the application of domestic surgical robot in oral and maxillofacial surgery, the author successfully completed a case of benign parotid tumor resection with the assistance of a domestic autonomous robot. The operation was successful, facial nerve function was preserved, and postoperative wound healing was good.


Assuntos
Neoplasias Parotídeas , Procedimentos Cirúrgicos Robóticos , Humanos , Neoplasias Parotídeas/cirurgia , Neoplasias Parotídeas/patologia , Glândula Parótida/cirurgia , Glândula Parótida/patologia , China
3.
Front Pharmacol ; 15: 1173240, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38584599

RESUMO

Rapamycin, an established mTOR inhibitor in clinical practice, is widely recognized for its therapeutic efficacy. Ridaforolimus, a non-prodrug rapalog, offers improved aqueous solubility, stability, and affinity compared to rapamycin. In recent years, there has been a surge in clinical trials involving ridaforolimus. We searched PubMed for ridaforolimus over the past decade and selected clinical trials of ridaforolimus to make a summary of the research progress of ridaforolimus in clinical trials. The majority of these trials explored the application of ridaforolimus in treating various tumors, including endometrial cancer, ovarian cancer, prostate cancer, breast cancer, renal cell carcinoma, and other solid tumors. These trials employed diverse drug combinations, incorporating agents such as ponatinib, bicalutamide, dalotuzumab, MK-2206, MK-0752, and taxanes. The outcomes of these trials unveiled the diverse potential applications of ridaforolimus in disease treatment. Our review encompassed analyses of signaling pathways, ridaforolimus as a single therapeutic agent, its compatibility in combination with other drugs, and an assessment of adverse events (AEs). We conclude by recommending further research to advance our understanding of ridaforolimus's clinical applications.

4.
Poult Sci ; 103(5): 103628, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38518667

RESUMO

This study sought to determine the relationship among broiler performance, organ development, and indicators of microbiota colonization. A total of 1,200 two-day-old male Ross 308 broiler chicks, divided among 3 cohorts of equal size, were housed in battery cages, and allotted based on body weight. On study d 11, birds were weighed, and birds with BW gain within the 10th and 90th percentiles were assigned to the Slow and Fast groups, respectively. Birds (n = 30 for each group) selected on d 11 were provided water and a corn-soybean meal-based diet ad libitum while maintained individually through study d 25 (i.e., a 14-d growth period). Parameters regarding growth performance, organ and intestine weights and lengths, and intestinal volatile fatty acid concentrations were measured. All data were analyzed by one-way ANOVA using the Mixed procedure of SAS. Fast birds exhibited greater (P < 0.001) BW gain and feed intake than slow birds, but feed conversion ratio (FCR) did not differ (P = 0.19). Additionally, Slow birds had higher (P < 0.05) relative weights (% of BW) for nearly all organs on d 11 and 25, most notably the gizzard, proventriculus, pancreas, and liver. Conversely, intestinal sections were longer (P < 0.05) in the Fast birds. Measurement of gut histomorphology did not show any notable differences between growth rate groups in terms of villi height, crypt depth, or their ratio for either time-point (P > 0.05). In terms of volatile fatty acid concentrations of luminal contents, acetate concentrations were 10.2% higher (P < 0.001) in the ileum of the Slow birds compared with Fast birds on d 25. Overall, the findings suggest that total BW gain is influenced by the development of metabolically active organs, as supported by lower weight gain in Slow birds with relatively larger organ weights and shorter intestinal lengths than their Fast counterparts. The general lack of differences in fermentation end-product concentrations in luminal contents does not rule out influence of the microbiota on growth rate of broilers, which warrants further investigation.

5.
Neurobiol Dis ; 194: 106468, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38460801

RESUMO

Intracerebral hemorrhage (ICH) is a subtype of stroke marked by elevated mortality and disability rates. Recently, mounting evidence suggests a significant role of ferroptosis in the pathogenesis of ICH. Through a combination of bioinformatics analysis and basic experiments, our goal is to identify the primary cell types and key molecules implicated in ferroptosis post-ICH. This aims to propel the advancement of ferroptosis research, offering potential therapeutic targets for ICH treatment. Our study reveals pronounced ferroptosis in microglia and identifies the target gene, cathepsin B (Ctsb), by analyzing differentially expressed genes following ICH. Ctsb, a cysteine protease primarily located in lysosomes, becomes a focal point in our investigation. Utilizing in vitro and in vivo models, we explore the correlation between Ctsb and ferroptosis in microglia post-ICH. Results demonstrate that ICH and hemin-induced ferroptosis in microglia coincide with elevated levels and activity of Ctsb protein. Effective alleviation of ferroptosis in microglia after ICH is achieved through the inhibition of Ctsb protease activity and protein levels using inhibitors and shRNA. Additionally, a notable increase in m6A methylation levels of Ctsb mRNA post-ICH is observed, suggesting a pivotal role of m6A methylation in regulating Ctsb translation. These research insights deepen our comprehension of the molecular pathways involved in ferroptosis after ICH, underscoring the potential of Ctsb as a promising target for mitigating brain damage resulting from ICH.


Assuntos
Lesões Encefálicas , Catepsina B , Ferroptose , Microglia , Humanos , Lesões Encefálicas/metabolismo , Catepsina B/genética , Catepsina B/metabolismo , Hemorragia Cerebral/patologia , Microglia/metabolismo , Animais , Camundongos
6.
IEEE Trans Biomed Eng ; PP2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38170654

RESUMO

OBJECTIVE: To develop a novel multi-TE MR spectroscopic imaging (MRSI) approach to enable label-free, simultaneous, high-resolution mapping of several molecules and their biophysical parameters in the brain. METHODS: The proposed method uniquely integrated an augmented molecular-component-specific subspace model for multi-TE 1H-MRSI signals, an estimation-theoretic experiment optimization (nonuniform TE selection) for molecule separation and parameter estimation, a physics-driven subspace learning strategy for spatiospectral reconstruction and molecular quantification, and a new accelerated multi-TE MRSI acquisition for generating high-resolution data in clinically relevant times. Numerical studies, phantom and in vivo experiments were conducted to validate the optimized experiment design and demonstrate the imaging capability offered by the proposed method. RESULTS: The proposed TE optimization improved estimation of metabolites, neurotransmitters and their T2's over conventional TE choices, e.g., reducing variances of neurotransmitter concentration by  âˆ¼ 40% and metabolite T2 by  âˆ¼ 60%. Simultaneous metabolite and neurotransmitter mapping of the brain can be achieved at a nominal resolution of 3.4 ×3.4×6.4 mm 3. High-resolution, 3D metabolite T2 mapping was made possible for the first time. The translational potential of the proposed method was demonstrated by mapping biochemical abnormality in a post-traumatic epilepsy (PTE) patient. CONCLUSION: The feasibility for high-resolution mapping of metabolites/neurotransmitters and metabolite T2's within clinically relevant time was demonstrated. We expect our method to offer richer information for revealing and understanding metabolic alterations in neurological diseases. SIGNIFICANCE: A novel multi-TE MRSI approach was presented that enhanced the technological capability of multi-parametric molecular imaging of the brain. The proposed method presents new technology development and application opportunities for providing richer molecular level information to uncover and comprehend metabolic changes relevant in various neurological applications.

7.
Health Sci Rep ; 7(1): e1792, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38196572

RESUMO

Background and Aims: To construct a bleeding events prediction model of nonvalvular atrial fibrillation (NVAF) patients receiving rivaroxaban. Methods: We conducted a retrospective cohort study in patients with NVAF who received rivaroxaban from June 2017 to March 2019. Demographic information and clinical characteristics were obtained from the electronic medical system. Univariate analysis was used to find the primary predictive factors of bleeding events in patients receiving rivaroxaban. Multiple analysis was conducted to screen the primary independent predictive factors selected from the univariate analysis. Finally, the independent influencing factors were applied to build a prediction model by using R software; then, a nomogram was established according to the selected variables visually, and the sensitivity and specificity of the model was evaluated. Results: Twelve primary predictive factors were selected by univariate analysis from 46 variables, and multivariate analysis showed that older age, higher prothrombin time (PT) values, history of heart failure and stroke were independent risk factors of bleeding events. The area under curve (AUC) for this novel nomogram model was 0.828 (95% CI: 0.763-0.894). The mean AUC over 10-fold stratified cross-validation was 0.787, and subgroup analysis validation also showed a satisfied AUC. In addition, the decision curve analysis showed that the PT in combination with CHA2DS2-VASc and HASBLED was more practical and accurate for predicting bleeding events than using CHA2DS2-VASc and HASBLED alone. Conclusions: PT in combination with CHA2DS2-VASc and HASBLED could be considered as a more practical and accurate method for predicting bleeding events in patients taking rivaroxaban.

8.
J Exp Bot ; 75(5): 1565-1579, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-37976240

RESUMO

Receptor-like kinases (RLKs) are major regulators of the plant immune response and play important roles in the perception and transmission of immune signals. RECEPTOR LIKE KINASE 902 (RLK902) is at the key node in leucine-rich repeat receptor-like kinase interaction networks and positively regulates resistance to the bacterial pathogen Pseudomonas syringae in Arabidopsis. However, the function of RLK902 in fungal disease resistance remains obscure. In this study, we found that the expression levels of OsRLK902-1 and OsRLK902-2, encoding two orthologues of RLK902 in rice, were induced by Magnaporthe oryzae, chitin, and flg22 treatment. osrlk902-1 and osrlk902-2 knockout mutants displayed enhanced susceptibility to M. oryzae. Interestingly, the osrlk902-1 rlk902-2 double mutant exhibited similar disease susceptibility, hydrogen peroxide production, and callose deposition to the two single mutants. Further investigation showed that OsRLK902-1 interacts with and stabilizes OsRLK902-2. The two OsRLKs form a complex with OsRLCK185, a key regulator in chitin-triggered immunity, and stabilize it. Taken together, our data demonstrate that OsRLK902-1 and OsRLK902-2, as well as OsRLCK185 function together in regulating disease resistance to M. oryzae in rice.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Magnaporthe , Oryza , Resistência à Doença/genética , Complexo Antígeno-Anticorpo/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Arabidopsis/metabolismo , Quitina/metabolismo , Oryza/metabolismo , Doenças das Plantas/microbiologia , Magnaporthe/fisiologia , Proteínas Quinases/metabolismo , Proteínas de Arabidopsis/metabolismo
9.
Nanoscale ; 16(2): 614-623, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38086654

RESUMO

Inorganic CsPbX3 (X = Cl, Br, I) perovskite nanocrystals (NCs) possess many advantageous optoelectronic properties, making them an attractive candidate for light emitting diodes, lasers, or photodetector applications. Such perovskite NCs can form extended assemblies that further modify their bandgap and emission wavelength. In this article, a facile direct synthesis of CsPbX3 NC assemblies that are 1 µm in size and are composed of 10 nm-sized NC building blocks is reported. The direct synthesis of these assemblies with a conventional hot-injection method of the NCs is achieved through the judicious selection of the solvent, ligands, and reaction stoichiometry. Only under selective reaction conditions where the surface ligand environment is tuned to enhance the hydrophobic interactions between ligand chains of neighbouring NCs is self-assembly achieved. These assemblies possess narrow and red-shifted photoluminescence compared to their isolated NC counterparts, which further expands the colour gamut that can be rendered from inorganic perovskites. This is demonstrated through simple down-converting light emitters.

10.
J Inflamm Res ; 16: 6179-6193, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38116368

RESUMO

Background: Gouty arthritis is characterized by the accumulation of monosodium urate crystals (MSU) in the synovial joints and surrounding tissues. Mastoparan M (Mast-M) is a biologically active peptide composed of 14 amino acids, extracted from wasp venom. This study aims to assess the impact of Mast-M on in vitro and in vivo gouty arthritis induced by lipolyaccharide (LPS) plus MSU crystal stimulation. Methods: PMA-differentiated THP-1 macrophages were pre-treated with Mast-M or left untreated, followed by stimulation with LPS and MSU crystals. Cell lysates were collected to assess the expression of the NLRP3 inflammasome, inflammatory signaling pathways, and oxidative stress. Furthermore, to evaluate the in vivo anti-inflammatory effect of Mast-M, an experimental acute gouty arthritis mouse model was established through intra-articular injection of MSU crystals. Results: Mast-M treatment demonstrated significant inhibition of the phosphorylation of MAPKs/NF-κB signaling pathways and reduction in oxidative stress expression in LPS and MSU-induced THP-1 macrophages. This resulted in the suppression of downstream NLRP3 inflammasome activation and IL-1ß release. In vivo, Mast-M effectively attenuated the inflammation induced by MSU in mice with gouty arthritis. Specifically, Mast-M reduced swelling in the paws, inhibited the infiltration of neutrophils and macrophages into periarticular tissue, and decreased the activation of the NLRP3 inflammasome and IL-1ß production. Conclusion: Mast-M significantly improves gouty arthritis, and its potential mechanism may be achieved by inhibiting the MAPK/NF-κB pathway and alleviating oxidative stress, thus suppressing the activation of NLRP3 inflammasomes.

11.
Neuropsychiatr Dis Treat ; 19: 2833-2840, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38149001

RESUMO

Objective: This study aims to elucidate the potential links between the GLU/GABA to GLN metabolic cycle disruptions and the onset of depressive and insomnia disorders following a stroke. We particularly focus on understanding if these disorders share a common underlying pathogenic mechanism. Methods: We examined 63 patients with post-stroke insomnia, 62 patients with post-stroke depression, and 18 healthy individuals. The study involved assessing insomnia using the Acute Insomnia Scale (AIS) and depression using the Hamilton Depression Rating Scale. We measured serum concentrations of GLN, GLU, and GABA and analyzed their correlations with AIS and HAMD scores. Results: Our results indicate no significant difference in the serum levels of GLN, GLU, and GABA between the post-stroke insomnia and depression groups. However, these levels were notably lower in both patient groups compared to the healthy control group. A negative correlation between AIS scores and GABA levels was observed in the post-stroke insomnia group, suggesting a potential link between GABAergic disturbances and insomnia. Conversely, no significant correlation was found between Hamilton Depression Rating Scale scores and the levels of GABA, GLU, or GLN in the post-stroke depression group. Conclusion: The study highlights that abnormalities in the GLU/GABA to GLN metabolic cycle, particularly the levels of GLN, GABA, and GAD, might be intricately linked to the pathogenesis of post-stroke insomnia and depression. Our findings suggest that GABAergic imbalances could be indicative of post-stroke insomnia, serving as potential biological markers for differential diagnosis in clinical settings. Further research is warranted to explore these relationships in greater depth, potentially leading to new diagnostic and therapeutic approaches for post-stroke neuropsychiatric disorders.

12.
J Chem Theory Comput ; 19(22): 8156-8165, 2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-37962975

RESUMO

Neural-network quantum states (NQS) employ artificial neural networks to encode many-body wave functions in a second quantization through variational Monte Carlo (VMC). They have recently been applied to accurately describe electronic wave functions of molecules and have shown the challenges in efficiency compared with traditional quantum chemistry methods. Here, we introduce a general nonstochastic optimization algorithm for NQS in chemical systems, which deterministically generates a selected set of important configurations simultaneously with energy evaluation of NQS. This method bypasses the need for Markov-chain Monte Carlo within the VMC framework, thereby accelerating the entire optimization process. Furthermore, this newly developed nonstochastic optimization algorithm for NQS offers comparable or superior accuracy compared to its stochastic counterpart and ensures more stable convergence. The application of this model to test molecules exhibiting strong electron correlations provides further insight into the performance of NQS in chemical systems and opens avenues for future enhancements.

13.
Materials (Basel) ; 16(22)2023 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-38005061

RESUMO

Nickel is widely used in industrial processes and plays a crucial role in many applications. However, most of the nickel resource mainly exists as nickel oxide in laterite nickel ore with complex composition, resulting in difficulty in upgrading the nickel content using physical separation methods. In this study, high-grade ferronickel concentrates were obtained through a carbothermal reduction and magnetic separation using laterite nickel ore and anthracite as raw materials. The effects of different types of additives (CaF2, Na2SO4, and H3BO3), carbon ratio (the molar ratio of oxygen atoms in the laterite nickel ore to carbon atoms in anthracite), and grinding time on the recoveries and grades of ferronickel concentrates were experimentally investigated, along with the microstructure and chemical composition of the products. CaF2 was proved to be the primary active additive in the aggregation and growth of the ferronickel particles and the improvement of the grade of the product. Under the optimal conditions of CaF2 addition of 9.85 wt%, carbon ratio of 1.4, and grinding time of 240 s, high-grade magnetically separable ferronickel concentrate with nickel grade 8.93 wt% and iron grade 63.96 wt% was successfully prepared. This work presents a practical method for the highly efficient recovery and utilization of iron and nickel from low-grade laterite nickel ore, contributing to the development of strategies for the sustainable extraction and utilization of nickel resources.

14.
Int J Gen Med ; 16: 5225-5234, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38021056

RESUMO

Purpose: To compare the clinical repair effects of leaving the defect empty and using Platelet-Rich Fibrin (PRF) combined with BIO-GENE artificial bone powder in patients with bone defects 6 months after jaw cystectomy. Patients and Methods: From June 2021 to June 2022, 70 patients who were admitted to the Department of Stomatology, Affiliated Hospital of Yanbian University, and were diagnosed with jaw cysts postoperatively were selected. All of the patients were divided into two groups according to random method, among which 35 patients who underwent cystectomy alone were recorded as group A, which served as blank control; 35 patients who underwent cystectomy and PRF combined with BIO-GENE artificial bone meal repaired bone defects during the same period were recorded as group B. 3D Slicer 5.0.3 software was used to reconstruct Cone Beam Computed Tomography (CBCT) after operation. In this study, the preoperative and postoperative CBCT data of the patients were analyzed using 3D Slicer 5.0.3 software in DICOM format to calculate the cleft volume before surgery and the newly formed bone volume after surgery. The osteogenesis rate was measured based on these calculations.The bone formation percentage in the bone defect area was recorded at 6 months, and the clinical curative effects of the two groups were compared. Results: After 6 months of surgery, the patients showed varying degrees of restoration in the jaw cyst area.The osteogenesis rate at 6 months in group A was 76.06±13.38%, while group B had a rate of 92.87±5.72%.The CBCT values in group B were higher than those in group A at 6 months post-surgery (P<0.05), t=-6.84.Group A and Group B showed a statistically significant difference. Conclusion: Compared with simple cystectomy, PRF combined with BIO-GENE artificial bone powder has a better effect on the speed of bone repair after cystectomy within 6 months and provides more favorable effects for the repair of postoperative dentition defects, and provides support to repair teeth after defects such as dental implants.

15.
Proc Natl Acad Sci U S A ; 120(43): e2303989120, 2023 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-37856546

RESUMO

The Periodic Law of Chemistry is one of the great discoveries in cultural history. Elements behaving chemically similar are empirically merged in groups G of a Periodic Table, each element with G valence electrons per neutral atom, and with upper limit G for the oxidation and valence numbers. Here, we report that among the usually mono- or di-valent s-block elements (G = 1 or 2), the heaviest members (87Fr, 88Ra, 119E, and 120E) with atomic numbers Z = 87, 88, 119, 120 form unusual 5- or 6-valent compounds at ambient conditions. Together with well-reported basic changes of valence at the end of the 6d-series, in the whole 7p-series, and for 5g6f-elements, it indicates that at the bottom of common Periodic Tables, the classic Periodic Law is not as straightforward as commonly expected. Specifically, we predict the feasible experimental synthesis of polyvalent [RaL-n] (n = 4, 6) compounds.

16.
Poult Sci ; 102(12): 103122, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37832186

RESUMO

Duck is an economically important poultry, and there is currently a major focus on improving its meat quality through breeding. There are wide variations in the growth regulation mechanisms of different duck breeds, that fundamental research on skeletal muscle growth is essential for understanding the regulation of unknown genes. The study aimed to broaden the understanding the duck skeletal muscle development and thereby to improve the performance of domestic ducks. In this study, RNA-seq data from skeletal muscles (breast muscle and leg muscle) of Pekin duck and Hanzhong Ma duck sampled at d 17, 21, and 27 of embryo (E17d, E21d, and E27d), as well as at 6-mo-old following birth (M6), to investigate and compare the mRNA temporal expression profiles and associated pathways that regulate skeletal myogenesis of different duck breeds. There were 331 to 1,440 annotated differentially expressed genes (DEGs) in breast muscle and 380 to 1,790 annotated DEGs in leg muscle from different databases between 2 duck breeds. Gene ontology (GO) enrichment in skeletal muscles indicated that these DEGs were mainly involved in biosynthetic process, developmental process, regulation of protein metabolic process and regulation of gene expression. KEGG analysis in skeletal muscles showed that a total of 41 DEGs were mapped to 7 KEGG pathways, including ECM-receptor interaction, focal adhesion, carbon metabolism, regulation of actin cytoskeleton, calcium signaling pathway, biosynthesis of amino acids and PPAR signaling pathway. The differential expression of 8 selected DEGs was verified by qRT-PCR, and the results were consistent with RNA-seq data. The identified DEGs, such as SDC, SPP1, PAK1, MYL9, PGK1, NOS1, PHGDH, TNNT2, FN1, and AQP4, were specially highlighted, indicating their associations with muscle development in the Pekin duck and Hanzhong Ma duck. This study provides a basis for revealing the differences in skeletal muscle development between Pekin duck and Hanzhong Ma duck.


Assuntos
Galinhas , Patos , Feminino , Animais , Patos/genética , Patos/metabolismo , RNA-Seq/veterinária , Galinhas/genética , Perfilação da Expressão Gênica/veterinária , Transcriptoma , Músculo Esquelético/metabolismo
17.
Org Lett ; 25(38): 6959-6963, 2023 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-37726896

RESUMO

The cross-coupling of epoxides with acyl chlorides or anhydrides by a nickel/titanocene dual catalytic system is established. A variety of synthetically useful ß-hydroxy ketones were obtained in good to high yields by using modified pyridine-oxazoline ligand. The reaction proceeds via the cooperation of titanocene-catalyzed ring-opening of epoxides and nickel-catalyzed acylation of the benzylic radical intermediate.

18.
J Control Release ; 363: 235-252, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37739016

RESUMO

Extracellular vesicles (EVs) are promising therapeutic carriers owing to their ideal size range and intrinsic biocompatibility. However, limited targeting ability has caused major setbacks in the clinical application of EV therapeutics. To overcome this, we genetically engineered natural free streptavidin (SA) on the cellular surface of bone marrow mesenchymal stem cells (BMSCs) and obtained typical EVs from these cells (BMSC-EVs). Biotin-coated gold nanoparticles confirmed the expression of SA on the membrane of EVs, which has a high affinity for biotinylated molecules. Using a squamous cell carcinoma model, we demonstrated that a pH-sensitive fusogenic peptide -modification of BMSC-EVs achieved targetability in the microenvironment of a hypoxic tumor to deliver anti-tumor drugs. Using EGFR+HER2- and EGFR-HER2+ breast cancer models, we demonstrated that anti-EGFR and anti-HER2 modifications of BMSC-EVs were able to specifically deliver drugs to EGFR+ and HER2+ tumors, respectively. Using a collagen-induced arthritis model, we confirmed that anti-IL12/IL23-modified BMSC-EVs specifically accumulated in the arthritic joint and alleviated inflammation. Administration of SA-overexpressing BMSC-EVs has limited immunogenicity and high safety in vivo, suggesting that BMSC-derived EVs are ideal drug delivery vehicle. These representative scenarios of targeting modification suggest that, using different biotinylated molecules, the SA-overexpressing BMSC-EVs could be endowed with different targetabilities, which allows BMSC-EVs to serve as a versatile platform for targeted drug delivery under various situations.


Assuntos
Neoplasias da Mama , Vesículas Extracelulares , Células-Tronco Mesenquimais , Nanopartículas Metálicas , MicroRNAs , Humanos , Feminino , Ouro/metabolismo , Vesículas Extracelulares/metabolismo , Neoplasias da Mama/metabolismo , Receptores ErbB/metabolismo , MicroRNAs/metabolismo , Microambiente Tumoral
19.
Proc Natl Acad Sci U S A ; 120(34): e2306950120, 2023 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-37590412

RESUMO

Hybrid voltage indicators (HVIs) are chemogenetic sensors that combines the superior photophysical properties of organic dyes and the genetic targetability of protein sensors to report transient membrane voltage changes. They exhibit boosted sensitivity in excitable cells such as neurons and cardiomyocytes. However, the voltage signals recorded during long-term imaging are severely diminished or distorted due to phototoxicity and photobleaching issues. To capture stable electrophysiological activities over a long time, we employ cyanine dyes conjugated with a cyclooctatetraene (COT) molecule as the fluorescence reporter of HVI. The resulting orange-emitting HVI-COT-Cy3 enables high-fidelity voltage imaging for up to 30 min in cultured primary neurons with a sensitivity of ~ -30% ΔF/F0 per action potential (AP). It also maximally preserves the signal of individual APs in cardiomyocytes. The far-red-emitting HVI-COT-Cy5 allows two-color voltage/calcium imaging with GCaMP6s in neurons and cardiomyocytes for 15 min. We leverage the HVI-COT series with reduced phototoxicity and photobleaching to evaluate the impact of drug candidates on the electrophysiology of excitable cells.


Assuntos
Dermatite Fototóxica , Miócitos Cardíacos , Humanos , Neurônios , Diagnóstico por Imagem , Corantes
20.
Technol Health Care ; 31(6): 2355-2361, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37483040

RESUMO

BACKGROUND: At present, the pathogenesis of post-stroke insomnia (PSI) is still inconclusive. OBJECTIVE: To explore the changes and significance of serum cholecystokinin-8 (CCK-8), substance P (SP), and 5-hydroxytryptamine (5-HT) in patients with PSI. METHODS: Ninety-one patients with stroke were selected as the research subjects, and according to the score of the Athens Insomnia Scale (AIS), they were divided into the insomnia group and the non-insomnia group. The serum levels of CCK-8, SP, and 5-HT in the two groups were compared to explore their relationships with PSI. RESULTS: Among the 91 patients, 56 were in the insomnia group and 35 were in the non-insomnia group, and the incidence of insomnia was 61.5%. There was no significant difference in the serum levels of CCK-8, SP, and 5-HT between the two groups (P= 0.696, 0.980, and 0.809, respectively). One-way analysis of variance showed that there was no significant correlation between the serum levels of CCK-8, SP, 5-HT, and the AIS score (P= 0.7393, 0.9581, and 0.5952, respectively). CONCLUSION: The incidence of PSI was relatively high, but it could not be proved that CCK-8, SP, and 5-HT were involved in the pathogenesis of PSI. There might exist other neurotransmitters involved in the pathophysiological process of PSI, which should be further explored.


Assuntos
Distúrbios do Início e da Manutenção do Sono , Acidente Vascular Cerebral , Humanos , Serotonina , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Distúrbios do Início e da Manutenção do Sono/etiologia , Substância P , Sincalida , Colecistocinina , Acidente Vascular Cerebral/complicações
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