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1.
Artículo en Inglés | MEDLINE | ID: mdl-39222205

RESUMEN

Combined deficiency of coagulation factor V (FV) and factor VIII (FVIII) is a rare bleeding disease caused by variants in either lectin mannose binding 1 (LMAN1) or multiple coagulation factor deficiency 2 (MCFD2) gene. Reducing the level of FVIII by inhibiting the LMAN1-MCFD2 complex may become a new anticoagulant approach. We aimed to find a new therapeutic option for anticoagulation by RNA interference (RNAi) targeting LMAN1 and MCFD2. siRNA sequences with cross-homology between mice and humans were designed based on LMAN1 or MCFD2 transcripts in NCBI and were screened with the Dual-Luciferase reporter assay. The optimal siRNAs were chemically modified and conjugated with three N-acetylgalactosamine molecules (GalNAc-siRNA), promoting their targeted delivery to the liver. The expression of LMAN1 and MCFD2 in cell lines or mice was examined by RT-qPCR and western blotting. For the mice administered with siRNA, we assessed their coagulation function by measuring APTT and the activity of FVIII factor. After administration, siRNAs GalNAc-LMAN1 and GalNAc-MCFD2 demonstrated effective and persistent LMAN1 and MCFD2 inhibition. 7 days after injection of 3mg/kg GalNAc-LMAN1, the LMAN1 mRNA levels reduced to 19.97% ± 3.78%. MCFD2 mRNA levels reduced to 32.22% ± 13.14% with injection of 3mg/kg GalNAc-MCFD2. After repeated administration, APTT was prolonged and the FVIII activity was remarkably decreased. The tail bleeding test of mice showed that the amount of bleeding in the treated group did not significantly increase compared with the control group. Our study confirms that therapy with RNAi targeting LMAN1-MCFD2 complex is effective and can be considered a viable option for anticoagulation drugs. However, the benefits and potential risk of bleeding in thrombophilic mice model needs to be evaluated.

2.
Mol Nutr Food Res ; : e2400098, 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39246232

RESUMEN

The objective of this study is to elucidate how Royal jelly (RJ) and 10-hydroxy-2-decanoic acid (10-HDA) prevents diabetic skin dysfunction by modulating the pyroptosis pathway. Type 2 diabetes models are induced by fat diet consumption and low dose of streptozotocin (STZ) in C57BL/6J mice and treated with RJ (100 mg kg-1 day-1) and 10-HDA, the major lipid component of royal jelly (100 mg kg-1 day-1) for 28 weeks. The results show that serum concentrations of glucose and triglyceride are significantly lower in the RJ group or 10-HDA than diabetes mellitus (DM) group. Compared to the control group, pyroptosis proteins, GSDMD, ASC, Caspase-1, and IL-1ß are increased in the skin of the diabetic model, accompanied by the activation of the Wnt/ß-catenin signal pathway. Further evaluations by RJ exhibit superior improvement of skin damage, repress activation of the Wnt/ß-catenin pathway, and attenuate keratinocyte pyroptosis, but 10-HDA cannot completely suppress the activation of Wnt/ß-catenin pathway and pyroptosis, which shows a relatively weak protective effect on skin damage which shows that RJ is a better effect on skin injury after DM.

3.
Pathol Res Pract ; 262: 155503, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39128411

RESUMEN

Gastric cancer (GC), a globally prevalent and lethal malignancy, continues to be a key research focus. However, due to its considerable heterogeneity and complex pathogenesis, the treatment and diagnosis of gastric cancer still face significant challenges. With the rapid development of spatial omics technology, which provides insights into the spatial information within tumor tissues, it has emerged as a significant tool in gastric cancer research. This technology affords new insights into the pathology and molecular biology of gastric cancer for scientists. This review discusses recent advances in spatial omics technology for gastric cancer research, highlighting its applications in the tumor microenvironment (TME), tumor heterogeneity, tumor genesis and development mechanisms, and the identification of potential biomarkers and therapeutic targets. Moreover, this article highlights spatial omics' potential in precision medicine and summarizes existing challenges and future directions. It anticipates spatial omics' continuing impact on gastric cancer research, aiming to improve diagnostic and therapeutic approaches for patients. With this review, we aim to offer a comprehensive overview to scientists and clinicians in gastric cancer research, motivating further exploration and utilization of spatial omics technology. Our goal is to improve patient outcomes, including survival rates and quality of life.


Asunto(s)
Biomarcadores de Tumor , Genómica , Neoplasias Gástricas , Microambiente Tumoral , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Neoplasias Gástricas/metabolismo , Humanos , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Medicina de Precisión , Proteómica/métodos
4.
J Mater Chem B ; 12(34): 8321-8334, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39099557

RESUMEN

Bone adhesives, as alternatives to traditional bone fracture treatment methods, have great benefits in achieving effective fixation and healing of fractured bones. However, current available bone adhesives have limitations in terms of weak mechanical properties, low adhesion strength, and inappropriate degradability, hindering their clinical applications. The development of bone adhesives with strong mechanical properties, adhesion strength, and appropriate degradability remains a great challenge. In this study, polyacrylic acid was incorporated with tetracalcium phosphate and O-phospho-L-serine to form a new bone adhesive via coordination and ionic interactions to achieve exceptional mechanical properties, adhesion strength, and degradability. The bone adhesive could achieve an initial adhesion strength of approximately 3.26 MPa and 0.86 MPa on titanium alloys and bones after 15 min of curing, respectively, and it increased to 5.59 MPa and 2.73 MPa, after 24 h of incubation in water or simulated body fluid (SBF). The compressive strength of the adhesive increased from 10.06 MPa to 72.64 MPa over two weeks, which provided sufficient support for the fractured bone. Importantly, the adhesive started to degrade after 6 to 8 weeks of incubation in SBF, which is beneficial to cell ingrowth and the bone healing process. In addition, the bone adhesives exhibited favorable mineralization capability, biocompatibility, and osteogenic activity. In vivo experiments showed that it has a better bone-healing effect compared with the traditional polymethyl methacrylate bone cement. These results demonstrate that the bone adhesive has great potential in the treatment of bone fractures.


Asunto(s)
Resinas Acrílicas , Cementos para Huesos , Resinas Acrílicas/química , Cementos para Huesos/química , Cementos para Huesos/farmacología , Animales , Ensayo de Materiales , Ratones , Propiedades de Superficie , Titanio/química
5.
Macromol Rapid Commun ; : e2400234, 2024 Jun 02.
Artículo en Inglés | MEDLINE | ID: mdl-38824415

RESUMEN

Invisible aligners have been widely used in orthodontic treatment but still present issues with plaque formation and oral mucosa abrasion, which can lead to complicated oral diseases. To address these issues, hydrophilic poly(sulfobetaine methacrylate) (polySBMA) coatings with lubricating, antifouling, and antiadhesive properties have been developed on the aligner materials (i.e., polyethylene terephthalate glycol, PETG) via a simple and feasible glycidyl methacrylate (GMA)-assisted coating strategy. Poly(GMA-co-SBMA) is grafted onto the aminated PETG surface via the ring-opening reaction of GMA (i.e., "grafting to" approach to obtain G-co-S coating), or a polySBMA layer is formed on the GMA-grafted PETG surface via free radical polymerization (i.e., "grafting from" approach to obtain G-g-S coating). The G-co-S and G-g-S coatings significantly reduce the friction coefficient of PETG surface. Protein adsorption, bacterial adhesion, and biofilm formation on the G-co-S- and G-g-S-coated surfaces are significantly inhibited. The performance of the coatings remains stable after storage in air or artificial saliva for 2 weeks. Both coatings demonstrate good biocompatibility in vitro and is not caused irritation to the oral mucosa of rats in vivo over 2 weeks. This study proposes a promising strategy for the development of invisible aligners with improved performance, which is beneficial for oral health treatment.

6.
Aging Dis ; 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38739940

RESUMEN

Programmed cell death is pivotal for several physiological processes, including immune defense. Further, it has been implicated in the pathogenesis of developmental disorders and the onset of numerous diseases. Multiple modes of programmed cell death, including apoptosis, pyroptosis, necroptosis, and ferroptosis, have been identified, each with their own unique characteristics and biological implications. In February 2023, Liu Xiaoguang and his team discovered "disulfidptosis," a novel pathway of programmed cell death. Their findings demonstrated that disulfidptosis is triggered in glucose-starved cells exhibiting high expression of a protein called SLC7A11. Furthermore, disulfidptosis is marked by a drastic imbalance in the NADPH/NADP+ ratio and the abnormal accumulation of disulfides like cystine. These changes ultimately lead to the destabilization of the F-actin network, causing cell death. Given that high SLC7A11 expression is a key feature of certain cancers, these findings indicate that disulfidptosis could serve as the basis of innovative anti-cancer therapies. Hence, this review delves into the discovery of disulfidptosis, its underlying molecular mechanisms and metabolic regulation, and its prospective applications in disease treatment.

7.
Nat Commun ; 15(1): 4231, 2024 May 18.
Artículo en Inglés | MEDLINE | ID: mdl-38762611

RESUMEN

N-type polycrystalline SnSe is considered as a highly promising candidates for thermoelectric applications due to facile processing, machinability, and scalability. However, existing efforts do not enable a peak ZT value exceeding 2.0 in n-type polycrystalline SnSe. Here, we realized a significant ZT enhancement by leveraging the synergistic effects of divacancy defect and introducing resonance level into the conduction band. The resonance level and increased density of states resulting from tungsten boost the Seebeck coefficient. The combination of the enhanced electrical conductivity (achieved by increasing carrier concentration through WCl6 doping and Se vacancies) and large Seebeck coefficient lead to a high power factor. Microstructural analyses reveal that the co-existence of divacancy defects (Se vacancies and Sn vacancies) and endotaxial W- and Cl-rich nanoprecipitates scatter phonons effectively, resulting in ultralow lattice conductivity. Ultimately, a record-high peak ZT of 2.2 at 773 K is achieved in n-type SnSe0.92 + 0.03WCl6.

8.
Artículo en Inglés | MEDLINE | ID: mdl-38593180

RESUMEN

Here, we combined Cd and In codoping with a simple hydrothermal synthesis method to prepare SnSe powders composed of nanorod-like flowers. After spark plasma sintering, its internal grains inherited well the morphological features of the precursor, and the multiscale microstructure included nanorod-shaped grains, high-density dislocations, and stacking faults, as well as abundant nanoprecipitates, resulting in an ultralow thermal conductivity of 0.15 W m-1 K-1 for the synthesized material. At the same time, Cd and In synergistically regulated the electrical conductivity and Seebeck coefficient of SnSe, leading to an enhanced power factor. Among them, Sn0.94Cd0.03In0.03Se achieved a peak ZT of 1.50 parallel to the pressing direction, representing an 87.5% improvement compared with pure SnSe. Notably, the material possesses isotropic ZT values parallel and perpendicular to the pressing direction, overcoming the characteristic anisotropy in thermal performance observed in previous polycrystalline SnSe-based materials. Our results provide a new strategy for optimizing the performance of thermoelectric materials through structural engineering.

9.
Appl Environ Microbiol ; 90(3): e0223723, 2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38315008

RESUMEN

The stability of microbial communities, especially among core taxa, is essential for supporting plant health. However, the impacts of disease infection on the stability of rhizosphere fungal core microbiome remain largely unexplored. In this study, we delved into the effects of root rot infestation on the community structure, function, network complexity, and stability of Sanqi fungal core microbiomes, employing amplicon sequencing combined with co-occurrence network and cohesion analyses. Our investigation revealed that root rot disease led to a decrease in the α-diversity but an increase in the ß-diversity of the Sanqi fungal core microbiomes in the rhizosphere. Notably, Ilyonectria, Plectosphaerella, and Fusarium emerged as indicator species in the rhizosphere core microbiome of root rot-infected Sanqi plants, while Mortierella predominated as the dominant biomarker taxa in healthy soils. Additionally, root rot diminished the complexity and modularity of the rhizosphere networks by reducing the metrics associated with nodes, edges, degrees, and modularity. Furthermore, root rot resulted in a reduction in the proportion of negative connections in the network and the negative/positive cohesion of the entire core fungal microbiome. Particularly noteworthy was the observation that root rot infection destabilized the rhizosphere core fungal microbiome by weakening the negative connectivity associated with beneficial agents. Collectively, these results highlight the significance of the negative connectivity of beneficial agents in ensuring the stability of core microbial community.IMPORTANCERoot rot disease has been reported as the most devastating disease in the production process of artificial cultivated Sanqi ginseng, which seriously threatens the Sanqi industry. This study provides valuable insights into how root rot influences microbial relationships within the community. These findings open up opportunities for disease prevention and the promotion of plant health by regulating microbial interactions. In summary, the research sheds light on the ecological consequences of root rot on rhizosphere fungal microbiomes and offers potential strategies for managing soil-borne diseases and enhancing plant health.


Asunto(s)
Medicamentos Herbarios Chinos , Micobioma , Microbiología del Suelo , Rizosfera , Hongos , Raíces de Plantas/microbiología , Suelo/química
10.
Small ; 20(28): e2311153, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38308409

RESUMEN

Here, a high peak ZT of ≈2.0 is reported in solution-processed polycrystalline Ge and Cd codoped SnSe. Microstructural characterization reveals that CdSe quantum dots are successfully introduced by solution process method. Ultraviolet photoelectron spectroscopy evinces that CdSe quantum dots enhance the density of states in the electronic structure of SnSe, which leads to a large Seebeck coefficient. It is found that Ge and Cd codoping simultaneously optimizes carrier concentration and improves electrical conductivity. The enhanced Seebeck coefficient and optimization of carrier concentration lead to marked increase in power factor. CdSe quantum dots combined with strong lattice strain give rise to strong phonon scattering, leading to an ultralow lattice thermal conductivity. Consequently, high thermoelectric performance is realized in solution-processed polycrystalline SnSe by designing quantum dot structures and introducing lattice strain. This work provides a new route for designing prospective thermoelectric materials by microstructural manipulation in solution chemistry.

11.
Small ; 20(25): e2310123, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38214404

RESUMEN

MnTe emerges as an enormous potential for medium-temperature thermoelectric applications due to its lead-free nature, high content of Mn in the earth's crust, and superior mechanical properties. Here, it is demonstrate that multiple valence band convergence can be realized through Pb and Ag incorporations, producing large Seebeck coefficient. Furthermore, the carrier concentration can be obviously enhance by Pb and Ag codoping, contributing to significant enhancement of power factor. Moreover, microstructural characterizations reveal that PbTe nanorods can be introduced into MnTe matrix by alloying Pb. This can modify the microstructure into all-scale hierarchical architectures (including PbTe nanorods, enhances point-defect scattering, dense dislocations and stacking faults), strongly lowering lattice thermal conductivity to a record low value of 0.376 W m-1 K-1 in MnTe system. As a result, an ultra-high ZT of 1.5 can be achieved in MnTe thermoelectric through all-scale hierarchical structuring, optimized carrier concentration, and valence band convergence, outperforming most of MnTe-based thermoelectric materials.

12.
Am J Orthod Dentofacial Orthop ; 165(2): 173-185, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37906245

RESUMEN

INTRODUCTION: Effective aligner hygiene is recognized as an important part of orthodontic treatments and oral hygiene. However, there is no effective cleansing method for removable aligners. METHODS: In this study, we incorporated tannic acid (TA) with cetylpyridinium chloride (CPC) to develop the TA-CPC complex. The antibacterial properties of 15.8 mg/mL TA-CPC against Escherichia coli and Staphylococcus aureus were evaluated in vitro, which were compared with 5.1 mg/mL TA, 10.7 mg/mL CPC, a commercial denture cleansing solution (YA; 15 mg/mL), and water. As for the assessment of stain-removal ability, the aligners stained by coffee were soaked in cleansing solutions, and the color changes (ΔE∗) were calculated on the basis of the CIE L∗a∗b∗ color system, and the National Bureau of Standards system was used for the clinical interpretation of the color change. Atomic force microscope examination, tensile property assessment, and wavelength dispersive x-ray fluorescence analysis were performed to investigate the material compatibility of TA-CPC, and Cell Counting Kit-8 assay and live/dead assay were used to test the cytotoxicity of TA-CPC. RESULTS: The results showed that TA-CPC had a positive zeta-potential, and cation-π interaction changed the chemical environments of the phenyl group in TA-CPC, resulting in greater inhibition zones of S. aureus and E. coli than other cleaners. The quantification of the biofilm biomass and the fluorescent intensities also reflected that the TA-CPC solution exhibited better antibacterial ability. As for the ability of stain removal, ΔE∗ value of group TA-CPC was 2.84 ± 0.55, whereas those of stained aligners immersed with deionized distilled water, TA, YA, and CPC were 10.26 ± 0.04, 9.54 ± 0.24, 5.93 ± 0.36, and 4.69 ± 0.35, respectively. The visual inspection and National Bureau of Standards ratings also showed that the color of stained aligners cleansed by TA-CPC was much lighter than those of the other groups. Meanwhile, TA-CPC had good compatibility with the aligner material and cells. CONCLUSIONS: TA-CPC is a promising strategy to inhibit the formation of biofilms and remove the stains on the aligners safely, which may disinfect the aligners to improve oral health and help keep the transparent appearances of aligners without impacting the morphology and mechanical properties.


Asunto(s)
Cetilpiridinio , Colorantes , Polifenoles , Humanos , Cetilpiridinio/farmacología , Colorantes/farmacología , Escherichia coli , Staphylococcus aureus , Antibacterianos/farmacología , Agua/farmacología
13.
Curr Cancer Drug Targets ; 24(2): 127-141, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37183458

RESUMEN

EBV promotes many cancers such as lymphoma, nasopharyngeal carcinoma, and gastric; Latent Membrane Protein 1 (LMP1) is considered to be a major oncogenic protein encoded by Epstein- Barr virus (EBV). LMP1 functions as a carcinogen in lymphoma and nasopharyngeal carcinoma, and LMP1 may also promote gastric cancer. The expression level of LMP1 in host cells is a key determinant in tumorigenesis and maintenance of virus specificity. By promoting cell immortalization and cell transformation, promoting cell proliferation, affecting immunity, and regulating cell apoptosis, LMP1 plays a crucial tumorigenic role in epithelial cancers. However, very little is currently known about LMP1 in Epstein-Barr virus-associated gastric cancer (EBVaGC); the main reason is that the expression level of LMP1 in EBVaGC is comparatively lower than other EBV-encoded proteins, such as The Latent Membrane Protein 2A (LMP2A), Epstein-Barr nuclear antigen 1 (EBNA1) and BamHI-A rightward frame 1 (BARF1), to date, there are few studies related to LMP1 in EBVaGC. Recent studies have demonstrated that LMP1 promotes EBVaGC by affecting The phosphatidylinositol 3-kinase- Akt (PI3K-Akt), Nuclear factor-kappa B (NF-κB), and other signaling pathways to regulate many downstream targets such as Forkhead box class O (FOXO), C-X-C-motif chemokine receptor (CXCR), COX-2 (Cyclooxygenase-2); moreover, the gene methylation induced by LMP1 in EBVaGC has become one of the characteristics that distinguish this gastric cancer (GC) from other types of gastric cancer and LMP1 also promotes the formation of the tumor microenvironment (TME) of EBVaGC in several ways. This review synthesizes previous relevant literature, aiming to highlight the latest findings on the mechanism of action of LMP1 in EBVaGC, summarize the function of LMP1 in EBVaGC, lay the theoretical foundation for subsequent new research on LMP1 in EBVaGC, and contribute to the development of novel LMP1-targeted drugs.


Asunto(s)
Infecciones por Virus de Epstein-Barr , Linfoma , Neoplasias Nasofaríngeas , Neoplasias Gástricas , Humanos , Herpesvirus Humano 4 , Infecciones por Virus de Epstein-Barr/complicaciones , Neoplasias Gástricas/metabolismo , Carcinoma Nasofaríngeo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Neoplasias Nasofaríngeas/metabolismo , Proteínas de la Membrana/metabolismo , Microambiente Tumoral , Proteínas Virales/metabolismo
14.
Neural Regen Res ; 19(8): 1696-1701, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38103234

RESUMEN

Brain homeostasis refers to the normal working state of the brain in a certain period, which is important for overall health and normal life activities. Currently, there is a lack of effective treatment methods for the adverse consequences caused by brain homeostasis imbalance. Snapin is a protein that assists in the formation of neuronal synapses and plays a crucial role in the normal growth and development of synapses. Recently, many researchers have reported the association between snapin and neurologic and psychiatric disorders, demonstrating that snapin can improve brain homeostasis. Clinical manifestations of brain disease often involve imbalances in brain homeostasis and may lead to neurological and behavioral sequelae. This article aims to explore the role of snapin in restoring brain homeostasis after injury or diseases, highlighting its significance in maintaining brain homeostasis and treating brain diseases. Additionally, it comprehensively discusses the implications of snapin in other extracerebral diseases such as diabetes and viral infections, with the objective of determining the clinical potential of snapin in maintaining brain homeostasis.

15.
Int Immunopharmacol ; 123: 110715, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37562294

RESUMEN

Periodontitis is the sixth major complication of diabetes. Gingiva, as an important component of periodontal tissues, serves as the first defense barrier against infectious stimuli. However, relatively little is known about cellular heterogeneity and cell-specific changes in gingiva in response to diabetes-associated periodontitis. To characterize molecular changes linking diabetes with periodontitis, we profiled single-cell transcriptome analyses of a total of 45,259 cells from rat gingiva with periodontitis under normoglycemic and diabetic condition. The single-cell profiling revealed that stromal and epithelial cells of gingiva contained inflammation-related subclusters enriched in functions of immune cell recruitment. Compared to normoglycemic condition, diabetes led to a reduction in epithelial basal cells, fibroblasts and smooth muscle cells in gingiva with periodontitis. Analysis of differentially expressed genes indicated that stromal and epithelial populations were reprogrammed towards pro-inflammatory phenotypes promoting immune cell recruitment in diabetes-related periodontitis. In aspect of immune cells, diabetes prominently enhanced neutrophil and M1 macrophage infiltration in periodontitis lesions. Cell-cell communications revealed enhanced crosstalk between stromal/epithelial cells and immune cells mediating by chemokine/chemokine receptor interplay in diabetes-associated periodontitis. Our findings deconvolved cellular heterogeneity of rat gingiva associated with periodontitis and diabetes, uncovered altered immune milieu caused by the disease, and revealed immunomodulatory functions of stromal and epithelial cells in gingival immune niche. The present study improves the understanding of the link between the diabetes and periodontitis and helps in formulating precise therapeutic strategies for diabetes-enhanced periodontitis.


Asunto(s)
Diabetes Mellitus , Periodontitis , Ratas , Animales , Células Epiteliales , Inflamación/patología , Diabetes Mellitus/patología , Encía/patología
16.
Brain Stimul ; 16(5): 1302-1309, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37633491

RESUMEN

BACKGROUND: Deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS) is an effective treatment for refractory epilepsy; however, seizure outcome varies among individuals. Identifying a reliable noninvasive biomarker to predict good responders would be helpful. OBJECTIVES: To test whether the functional connectivity between the ANT-DBS sites and the seizure foci correlates with effective seizure control in refractory epilepsy. METHODS: We performed a proof-of-concept pilot study of patients with focal refractory epilepsy receiving ANT-DBS. Using normative human connectome data derived from 1000 healthy participants, we investigated whether intrinsic functional connectivity between the seizure foci and the DBS site was associated with seizure outcome. We repeated this analysis controlling for the extent of seizure foci, distance between the seizure foci and DBS site, and using functional connectivity of the ANT instead of the DBS site to test the contribution of variance in DBS sites. RESULTS: Eighteen patients with two or more seizure foci were included. Greater functional connectivity between the seizure foci and the DBS site correlated with more favorable outcome. The degree of functional connectivity accounted for significant variance in clinical outcomes (DBS site: |r| = 0.773, p < 0.001 vs ANT-atlas: |r| = 0.715, p = 0.001), which remained significant when controlling for the extent of the seizure foci (|r| = 0.773, p < 0.001) and the distance between the seizure foci and DBS site (|r| = 0.777, p < 0.001). Significant correlations were independent of variance in the DBS sites (|r| = 0.148, p = 0.57). CONCLUSION: These findings suggest that functional connectomic profile is a potential reliable non-invasive biomarker to predict ANT-DBS outcomes. Accordingly, the identification of ANT responders could decrease the surgical risk for patients who may not benefit and optimize the cost-effective allocation of health care resources.


Asunto(s)
Núcleos Talámicos Anteriores , Conectoma , Estimulación Encefálica Profunda , Epilepsia Refractaria , Epilepsias Parciales , Humanos , Epilepsia Refractaria/terapia , Proyectos Piloto , Núcleos Talámicos Anteriores/fisiología , Convulsiones/terapia , Biomarcadores , Epilepsias Parciales/terapia
17.
Molecules ; 28(13)2023 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-37446753

RESUMEN

Conjugated polymers (CPs) have attracted much attention in the fields of chemistry, medicine, life science, and material science. Researchers have carried out a series of innovative researches and have made significant research progress regarding the unique photochemical and photophysical properties of CPs, expanding the application range of polymers. CPs are polymers formed by the conjugation of multiple repeating light-emitting units. Through precise control of their structure, functional molecules with different properties can be obtained. Fluorescence probes with different absorption and emission wavelengths can be obtained by changing the main chain structure. By modifying the side chain structure with water-soluble groups or selective recognition molecules, electrostatic interaction or specific binding with specific targets can be achieved; subsequently, the purpose of selective recognition can be achieved. This article reviews the research work of CPs in cell imaging, tumor diagnosis, and treatment in recent years, summarizes the latest progress in the application of CPs in imaging, tumor diagnosis, and treatment, and discusses the future development direction of CPs in cell imaging, tumor diagnosis, and treatment.


Asunto(s)
Neoplasias , Polímeros , Humanos , Polímeros/uso terapéutico , Polímeros/química , Diagnóstico por Imagen , Neoplasias/diagnóstico por imagen , Neoplasias/terapia , Solubilidad , Agua/química
18.
Front Pharmacol ; 14: 1117542, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37214477

RESUMEN

Neurological diseases such as traumatic brain injury, cerebral ischemia, Parkinson's, and Alzheimer's disease usually occur in the central and peripheral nervous system and result in nervous dysfunction, such as cognitive impairment and motor dysfunction. Long-term clinical intervention is necessary for neurological diseases where neural stem cell transplantation has made substantial progress. However, many risks remain for cell therapy, such as puncture bleeding, postoperative infection, low transplantation success rate, and tumor formation. Sustained drug delivery, which aims to maintain the desired steady-state drug concentrations in plasma or local injection sites, is considered as a feasible option to help overcome side effects and improve the therapeutic efficiency of drugs on neurological diseases. Natural polymers such as silk fibroin have excellent biocompatibility, which can be prepared for various end-use material formats, such as microsphere, gel, coating/film, scaffold/conduit, microneedle, and enables the dynamic release of loaded drugs to achieve a desired therapeutic response. Sustained-release drug delivery systems are based on the mechanism of diffusion and degradation by altering the structures of silk fibroin and drugs, factors, and cells, which can induce nerve recovery and restore the function of the nervous system in a slow and persistent manner. Based on these desirable properties of silk fibroin as a carrier with sustained-release capacity, this paper discusses the role of various forms of silk fibroin-based drug delivery materials in treating neurological diseases in recent years.

19.
J Chem Neuroanat ; 128: 102229, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36592695

RESUMEN

Rab7 belongs to the Ras small GTPase superfamily, and abnormal expression of Rab7 can cause neuropathy and lipid metabolism diseases. Studies have shown that Rab7 plays a crucial role in the inner membrane translocase. However, the role of Rab7 in the regulatory mechanisms of cell survival in spinal cord injury remains unknown. We used a rat spinal cord injury (SCI) model to explore the cellular localization and expression of Rab7 after SCI in this study. Western blot analysis showed that Rab7 was expressed in the spinal cord tissue. On the first day, it significantly increased and peaked after SCI on the third day. Furthermore, western blotting also demonstrated that pyroptosis-related protein Gasdermin D (GSDMD), Caspase-1, apoptosis-associated speck-like protein (ASC) expression peaked after the third-day post-injury. Importantly, the immunohistochemistry analysis revealed that Rab7 was completely colocalized with ASC in neurons after SCI. These results suggested that Rab7 was colocalized with NeuN and ASC, involved in the pyroptosis of neurons, and closely related to the spinal cord after injury.


Asunto(s)
Piroptosis , Traumatismos de la Médula Espinal , Animales , Ratas , Neuronas/metabolismo , Ratas Sprague-Dawley , Médula Espinal/metabolismo , Traumatismos de la Médula Espinal/metabolismo , Regulación hacia Arriba
20.
J Cancer Res Clin Oncol ; 149(9): 6675-6691, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-36639531

RESUMEN

Bacteria have been found in tumors for over 100 years, but the irreproducibility of experiments on bacteria, the limitations of science and technology, and the contamination of the host environment have severely hampered most research into the role of bacteria in carcinogenesis and cancer treatment. With the development of molecular tools and techniques (e.g., macrogenomics, metabolomics, lipidomics, and macrotranscriptomics), the complex relationships between hosts and different microorganisms are gradually being deciphered. In the past, attention has been focused on the impact of the gut microbiota, the site where the body's microbes gather most, on tumors. However, little is known about the role of microbes from other sites, particularly the intratumor microbiota, in cancer. In recent years, an increasing number of studies have identified the presence of symbiotic microbiota within a large number of tumors, bringing the intratumor microbiota into the limelight. In this review, we aim to provide a better understanding of the role of the intratumor microbiota in cancer, to provide direction for future experimental and translational research, and to offer new approaches to the treatment of cancer and the improvement of patient prognosis.


Asunto(s)
Microbioma Gastrointestinal , Microbiota , Neoplasias , Humanos , Carcinogénesis , Metabolómica
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