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1.
World J Clin Cases ; 12(19): 3785-3790, 2024 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-38994292

RESUMEN

BACKGROUND: Chronic sinusitis is a kind of chronic suppurative inflammation of the sinus mucosa. Nasal endoscopy is a good method to treat nasal polyps. However postoperative rehabilitation and care should not be neglected. AIM: To investigate the Effect of nursing intervention on the rehabilitation of patients with chronic sinusitis and nasal polyps (CSNPS) after nasal endoscopy. METHODS: A total of 129 patients with CSNPS hospitalized from February 2017 to February 2019 were studied. Using the digital parity method, we investigated nursing cooperation strategies for endoscopic surgery. The comparison group (64 cases): Surgical nursing was carried out with traditional nursing measures; experimental group (65 cases): Surgical nursing was carried out by traditional nursing countermeasures + comprehensive nursing measures. We compared postoperative recovery rates, nursing satisfaction rates, and nasal cavity ratings between the two groups. RESULTS: Experimental group patients with CSNPS had a significantly higher recovery rate (98.46%) compared to the control group (79.69%). This difference was statistically significant (χ 2 = 11.748, P < 0.05). Additionally, the satisfaction rate with treatment was also significantly higher in the experimental group (98.46%) compared to the control group (79.69%), with a statistically significant difference (χ 2 = 11.748, P < 0.05). Before nursing, there was no significant difference in sinus nasal cavity scores between the experimental group (20.29 ± 7.25 points) and the control group (20.30 ± 7.27 points) (t = 0.008, P > 0.05). However, after nursing, the sinus nasal cavity score in the experimental group (8.85 ± 3.22 points) was significantly lower than that in the control group (14.99 ± 5.02 points) (t = 8.282, P < 0.05). CONCLUSION: Comprehensive nursing intervention in patients with CSNPS can significantly improve the total recovery rate after endoscopic surgery.

2.
J Pain Res ; 17: 1793-1804, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38799277

RESUMEN

Acute postsurgical pain (APSP) has received growing attention as a surgical outcome. When poorly controlled, APSP can affect short- and long-term outcomes in patients. Despite the steady increase in awareness about postoperative pain and standardization of pain prevention and treatment strategies, moderate-to-severe APSP is frequently reported in clinical practice. This is possibly because pain varies widely among individuals and is influenced by distinct factors, such as demographic, perioperative, psychological, and genetic factors. This review investigates the risk factors for APSP, including gender, age, obesity, smoking history, preoperative pain history, pain sensitivity, preoperative anxiety, depression, pain catastrophizing, expected postoperative pain, surgical fear, and genetic polymorphisms. By identifying patients having an increased risk of moderate-to-severe APSP at an early stage, clinicians can more effectively manage individualized analgesic treatment protocols with a combination of pharmacological and non-pharmacological interventions. This would alleviate the transition from APSP to chronic pain and reduce the severity of APSP-induced chronic physical disability and social psychological distress.

3.
J Ethnopharmacol ; 327: 118002, 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38437890

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Polygonati Rhizome (PR) is a plant that is extensively widespread in the temperate zones of the Northern Hemisphere. It is a member of the Polygonatum family of Asparagaceae. PR exhibits diverse pharmacological effects and finds applications in ethnopharmacology, serving as a potent tonic for more than two millennia. PR's compounds endow it with various pharmacological properties, including anti-aging, antioxidant, anti-fatigue, anti-inflammatory, and sleep-enhancing effects, as well as therapeutic potential for osteoporosis and age-related diseases. AIM OF THE STUDY: This review seeks to offer a thorough overview of the processing, purification, extraction, structural characterization, and biosynthesis pathways of PR. Furthermore, it delves into the anti-aging mechanism of PR, using organ protection as an entry point. MATERIALS AND METHODS: Information on PR was obtained from scientific databases (Google Scholar, Web of Science, ScienceDirect, SciFinder, PubMed, CNKI) and books, doctoral theses, and master's dissertations. RESULTS: In this investigation, 49 polysaccharides were extracted from PR, and the impact of various processing, extraction, and purification techniques on the structure and activity of these polysaccharides was evaluated. Additionally, 163 saponins and 46 flavonoids were identified, and three key biosynthesis pathways of secondary metabolites were outlined. Notably, PR and Polygonat Rhizomai polysaccharides (PRP) exhibit remarkable protective effects against age-induced injuries to the brain, liver, kidney, intestine, heart, and vessels, thereby promoting longevity and ameliorating the aging process. CONCLUSIONS: PR, a culinary and therapeutic herb, is rich in active components and pharmacological activities. Based on this review, PR plays a meaningful role in lifespan extension and anti-aging, which can be attributed to PRP. Future research should delve deeper into the structural aspects of PRP that underlie its anti-aging effects and explore potential synergistic interactions with other compounds. Moreover, exploring the potential applications of PR in functional foods and pharmaceutical formulations is recommended to advance the development of industries and resources focused on healthy aging.


Asunto(s)
Fitoterapia , Extractos Vegetales , Fitoterapia/métodos , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Extractos Vegetales/química , Rizoma , Etnofarmacología , Polisacáridos , Fitoquímicos/farmacología , Fitoquímicos/uso terapéutico
5.
Micromachines (Basel) ; 15(2)2024 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-38398936

RESUMEN

In recent years, the development of terahertz (THz) technology has attracted significant attention. Various tunable devices for THz waves (0.1 THz-10 THz) have been proposed, including devices that modulate the amplitude, polarization, phase, and absorption. Traditional metal materials are often faced with the problem of non-adjustment, so the designed terahertz devices play a single role and do not have multiple uses, which greatly limits their development. As an excellent phase change material, VO2's properties can be transformed by external temperature stimulation, which provides new inspiration for the development of terahertz devices. To address these issues, this study innovatively combines metamaterials with phase change materials, leveraging their design flexibility and temperature-induced phase transition characteristics. We have designed a THz intelligent absorber that not only enables flexible switching between multiple functionalities but also achieves precise performance tuning through temperature stimulation. Furthermore, we have taken into consideration factors such as the polarization mode, environmental temperature, structural parameters, and incident angle, ensuring the device's process tolerance and environmental adaptability. Additionally, by exploiting the principle of localized surface plasmon resonance (LSPR) accompanied by local field enhancement, we have monitored and analyzed the resonant process through electric field characterization. In summary, the innovative approach and superior performance of this structure provide broader insights and methods for THz device design, contributing to its theoretical research value. Moreover, the proposed absorber holds potential for practical applications in electromagnetic invisibility, shielding, modulation, and detection scenarios.

6.
Microbiol Spectr ; : e0370723, 2024 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-38353552

RESUMEN

Long-term care facilities (LTCFs) for older people play an important and unique role in multidrug-resistant organism transmission. Herein, we investigated the genetic characteristics of mobile colistin resistance gene (mcr-1)-carrying Escherichia coli strains isolated from wastewater of LTCFs in Shanghai. Antimicrobial susceptibility test was carried out by agar dilution methods. Whole-genome sequencing and plasmid sequencing were conducted, and resistance genes and sequence types of colistin in E. coli isolates were analyzed. Core genome multilocus sequence typing (cgMLST) analysis was performed by the Ridom SeqSphere+ software. Phylogenetic tree through the maximum likelihood method was constructed by MEGA X. Out of 306 isolates, only 1 E. coli named ECSJ33 was found, and the plasmid pECSJ33 from ECSJ33 harbored the mcr-1 gene that was located with 59,080 bp belonging to IncI2 type. The plasmid pECSJ33 was capable of conjugation with an efficiency of 2.9 × 10-2. Bioinformatic analysis indicated pECSJ33 shared backbone with the previously reported mcr-1-harboring pHNGDF93 isolated from fish source. Moreover, the cgMLST analysis revealed that ECSJ33 belongs to different lineages from those reported from previous E. coli strains but shared high similarity to NCTC11129 in cluster 11. The phylogenetic tree revealed MCR-1 of ECSJ33 in this study was mostly of animal food origin and that they were closely related. Our study firstly reports detection of genome sequence of a multidrug-resistant mcr-1-harboring E. coli ST155 from wastewater of LTCF source in China. The data may prove that the plasmid pECSJ33 belongs to food origin and help to understand the antimicrobial resistance mechanisms and genomic features of colistin resistance under One Health approach.IMPORTANCEOne Escherichia coli named ECSJ33 was found from wastewater of a long-term care facility (LTCF) and the plasmid pECSJ33 from ECSJ33 harbored the mobile colistin resistance gene (mcr-1) that was located with 59,080 bp belonging to IncI2 type, which was capable of conjugation with an efficiency of 2.9 × 10-2. This paper firstly reports an mcr-1-carrying E. coli strain ST155 isolated from LTCF in China. Comparative genomics analysis indicated pECSJ33 shared backbone with the previously reported mcr-1-harboring pHNGDF93 isolated from fish source. The phylogenetic tree revealed MCR-1 protein of ECSJ33 in this study was mostly of animal food origin and that they were closely related. Therefore, the pECSJ33 could be considered as food-origin transmission mcr-1-harboring plasmid.

7.
Neurobiol Dis ; 190: 106375, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38092269

RESUMEN

Patients with chronic pain often experience memory impairment, but the underlying mechanisms remain elusive. The myelin sheath is crucial for rapid and accurate action potential conduction, playing a pivotal role in the development of cognitive abilities in the central nervous system. The study reveals that myelin degradation occurs in the hippocampus of chronic constriction injury (CCI) mice, which display both chronic pain and memory impairment. Using fiber photometry, we observed diminished task-related neuronal activity in the hippocampus of CCI mice. Interestingly, the repeated administration with clemastine, which promotes myelination, counteracts the CCI-induced myelin loss and reduced neuronal activity. Notably, clemastine specifically ameliorates the impaired memory without affecting chronic pain in CCI mice. Overall, our findings highlight the significant role of myelin abnormalities in CCI-induced memory impairment, suggesting a potential therapeutic approach for treating memory impairments associated with neuropathic pain.


Asunto(s)
Dolor Crónico , Clemastina , Humanos , Animales , Ratones , Clemastina/metabolismo , Dolor Crónico/tratamiento farmacológico , Dolor Crónico/metabolismo , Vaina de Mielina/metabolismo , Sistema Nervioso Central , Trastornos de la Memoria/tratamiento farmacológico , Trastornos de la Memoria/etiología , Trastornos de la Memoria/metabolismo , Hipocampo/metabolismo
8.
CNS Neurosci Ther ; 30(1): e14554, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-38105652

RESUMEN

AIMS: Sevoflurane is widely used for general anesthesia in children. Previous studies reported that multiple neonatal exposures to sevoflurane can induce long-term cognitive impairment in adolescent rats, but the underlying mechanisms were not defined. METHODS: Postnatal day 6 (P6) to P8 rat pups were exposed to 30% oxygen with or without 3% sevoflurane balanced with air. The Y maze test (YMT) and Morris water maze (MWM) tests were performed in some cohorts from age P35 to assess cognitive functions, and their brain samples were harvested at age P14, 21, 28, 35, and 42 for measurements of various molecular entities and in vivo electrophysiology experiments at age P35. RESULTS: Sevoflurane exposure resulted in cognitive impairment that was associated with decreased synCAM1 expression in parvalbumin (PV) interneurons, a reduction of PV phenotype, disturbed gamma oscillations, and dendritic spine loss in the hippocampal CA3 region. Enriched environment (EE) increased synCAM1 expression in the PV interneurons and attenuated sevoflurane-induced cognitive impairment. The synCAM1 overexpression by the adeno-associated virus vector in the hippocampal CA3 region restored sevoflurane-induced cognitive impairment, PV phenotype loss, gamma oscillations decrease, and dendritic spine loss. CONCLUSION: Our data suggested that neonatal sevoflurane exposure results in cognitive impairment through decreased synCAM1 expression in PV interneurons in the hippocampus.


Asunto(s)
Disfunción Cognitiva , Parvalbúminas , Humanos , Niño , Animales , Ratas , Sevoflurano/toxicidad , Animales Recién Nacidos , Parvalbúminas/metabolismo , Disfunción Cognitiva/inducido químicamente , Disfunción Cognitiva/metabolismo , Interneuronas/metabolismo , Aprendizaje por Laberinto/fisiología , Hipocampo/metabolismo
9.
Front Med (Lausanne) ; 10: 1251088, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38020118

RESUMEN

Signal transducer and activator of transcription 3 (STAT3) is a member of the STAT protein family implicated in the development of infantile-onset multisystem autoimmune disease. STAT3-related autoimmune disease is characterized by multiorgan autoimmunity, lymphoproliferative disease, and recurrent infections. The presentation is variable, with some patients also developing neonatal diabetes mellitus and interstitial lung disease. Gain-of-function variants in the Src homology 2 domain, leading to autophosphorylation and activation of STAT3, have been previously reported in patients with disease. Here, we report a patient with a novel missense variant, p.Glu616Ala, in STAT3 presenting with infantile-onset multisystem autoimmune disease.

12.
Risk Manag Healthc Policy ; 16: 1391-1401, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37560133

RESUMEN

Objective: Through analyzing the characteristics and influencing factors of adverse drug reactions/adverse events (ADR/ADE) in a hospital to promote rational drug use in the clinic. Methods: A total of 1221 ADR/ADE reports collected from a hospital in 2022 were retrieved through the National Adverse Drug Reaction Monitoring Center. The effective reports were screened according to the Guiding Principles for Collection and Reporting of Individual Adverse Drug Reactions, and classified the standardized drugs. The systems/organs and main clinical symptoms affected by ADR/ADE were classified according to the WHO Glossary of Adverse Drug Reaction Terms. The severity, age and gender, occupational distribution, drug category, route of administration, drug dosage form, system/organ involved, and main clinical symptoms of ADR/ADE reports were analyzed. Results: Among 1221 ADR/ADE reports, 890 cases (75.27%) reported by doctors; 144 cases (11.79%) were serious; Precisely 49.22% of ADR/ADE occurred in patients aged 51 to 70 years old; The highest incidence of adverse reactions was 636 cases (52.09%) by intravenous infusion, 406 cases (33.25%) by oral administration. The top categories of reported cases were anti-infective drugs (29.40%) and anti-tumor drugs (27.52%); Systems/organs involved in ADR/ADE were mainly the skin and its accessories (24.96%) and blood system (21.35%). 166 cases were cured, 893 cases were symptomatic, 160 cases were unknown, and 2 cases had sequelae. Conclusion: The occurrence of ADR/ADE is related to many influencing factors such as age, drug categories, and route of administration. Therefore, it is recommended that hospitals strengthen the monitoring of ADR/ADE, especially the elderly, anti-infective drugs and intravenous administration.

13.
Life Sci ; 327: 121839, 2023 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-37290666

RESUMEN

AIM: 6S-5-methyltetrahydrofolate is the predominant form of dietary folate in circulation and is used as a crystalline form of calcium salt (MTHF-Ca). Reports revealed that MTHF-Ca was more safe than folic acid, a synthetic and highly stable version of folate. Folic acid has been reported to have anti-inflammatory effects. The study's objective was to assess the anti-inflammatory effect of MTHF-Ca in vitro and in vivo. MAIN METHODS: In vitro, the ROS production was assessed by H2DCFDA, and nuclear translocation of NF-κB were evaluated by the NF-κB nuclear translocation assay kit. Interleukin-6 (IL-6), interleukin-1ß (IL-1ß), and tumor necrosis factor-alpha (TNF-α) were assessed using ELISA. In vivo, ROS production was assessed by H2DCFDA, neutrophils and macrophages recruitment were evaluated in tail transection-induced and CuSO4-induced zebrafish inflammation models. Expression of inflammation related genes were also investigated based on CuSO4-induced zebrafish inflammation model. KEY FINDINGS: MTHF-Ca treatment decreased LPS-induced ROS production, inhibited nuclear translocation of NF-κB and decreased the levels of IL-6, IL-1ß and TNF-α in RAW264.7 cells. In addition, MTHF-Ca treatment inhibited ROS production, suppressed the recruitment of neutrophils and macrophages, and reduced the expression of inflammation related genes, including jnk, erk, nf-κb, myd88, p65, tnf-α, and il-1b in zebrafish larvae. SIGNIFICANCE: MTHF-Ca may play an anti-inflammatory role by reducing the recruitment of neutrophils and macrophages and keeping the low levels of proinflammatory mediators and cytokines. MTHF-Ca may have a potential role in the treatment of inflammatory diseases.


Asunto(s)
FN-kappa B , Pez Cebra , Ratones , Animales , Pez Cebra/metabolismo , FN-kappa B/metabolismo , Calcio , Interleucina-6/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Especies Reactivas de Oxígeno , Antiinflamatorios/uso terapéutico , Inflamación/metabolismo , Células RAW 264.7 , Calcio de la Dieta , Ácido Fólico , Lipopolisacáridos/farmacología
14.
Neurobiol Dis ; 182: 106155, 2023 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-37182721

RESUMEN

Neuropathic pain, a severe clinical symptom, significantly affects the quality of life in the patients. The molecular mechanisms underlying neuropathic pain have been the focus of research in recent decades; however, the neuronal circuit-mediated mechanisms associated with this disorder remain poorly understood. Here, we report that a projection from the lateral hypothalamus (LH) glutamatergic neurons to the lateral habenula (LHb), an excitatory LH-LHb neuronal circuit, participates in nerve injury-induced nociceptive hypersensitivity. LH glutamatergic neurons are activated and display enhanced responses to normally non-noxious stimuli following chronic constriction injury. Chemogenetic inhibition of LH glutamatergic neurons or excitatory LH-LHb circuit blocked CCI-induced nociceptive hypersensitivity. Activation of the LH-LHb circuit led to augmented responses to mechanical and thermal stimuli in mice without nerve injury. These findings suggest that LH neurons and their triggered LH-LHb circuit participate in central mechanisms underlying neuropathic pain and may be targets for the treatment of this disorder.


Asunto(s)
Habénula , Neuralgia , Ratones , Animales , Área Hipotalámica Lateral , Calidad de Vida , Hipotálamo/fisiología , Neuralgia/etiología
15.
Pharmaceutics ; 15(4)2023 Apr 21.
Artículo en Inglés | MEDLINE | ID: mdl-37111792

RESUMEN

Anticancer peptides and polymers represent an emerging field of tumor treatment and can physically interact with tumor cells to address the problem of multidrug resistance. In the present study, poly(l-ornithine)-b-poly(l-phenylalanine) (PLO-b-PLF) block copolypeptides were prepared and evaluated as macromolecular anticancer agents. Amphiphilic PLO-b-PLF self-assembles into nanosized polymeric micelles in aqueous solution. Cationic PLO-b-PLF micelles interact steadily with the negatively charged surfaces of cancer cells via electrostatic interactions and kill the cancer cells via membrane lysis. To alleviate the cytotoxicity of PLO-b-PLF, 1,2-dicarboxylic-cyclohexene anhydride (DCA) was anchored to the side chains of PLO via an acid-labile ß-amide bond to fabricate PLO(DCA)-b-PLF. Anionic PLO(DCA)-b-PLF showed negligible hemolysis and cytotoxicity under neutral physiological conditions but recovered cytotoxicity (anticancer activity) upon charge reversal in the weakly acidic microenvironment of the tumor. PLO-based polypeptides might have potential applications in the emerging field of drug-free tumor treatment.

16.
J Transl Med ; 21(1): 135, 2023 02 22.
Artículo en Inglés | MEDLINE | ID: mdl-36814278

RESUMEN

Cognitive function is an important ability of the brain, but cognitive dysfunction can easily develop once the brain is injured in various neuropathological conditions or diseases. Photobiomodulation therapy is a type of noninvasive physical therapy that is gradually emerging in the field of neuroscience. Transcranial photobiomodulation has been commonly used to regulate neural activity in the superficial cortex. To stimulate deeper brain activity, advanced photobiomodulation techniques in conjunction with photosensitive nanoparticles have been developed. This review addresses the mechanisms of photobiomodulation on neurons and neural networks and discusses the advantages, disadvantages and potential applications of photobiomodulation alone or in combination with photosensitive nanoparticles. Photobiomodulation and its associated strategies may provide new breakthrough treatments for cognitive improvement.


Asunto(s)
Terapia por Luz de Baja Intensidad , Enfermedades del Sistema Nervioso , Humanos , Terapia por Luz de Baja Intensidad/métodos , Encéfalo , Cognición , Neuronas
17.
J Nanobiotechnology ; 21(1): 52, 2023 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-36765377

RESUMEN

Inflammatory depression is closely related to neuroinflammation. However, current anti-inflammatory drugs have low permeability to cross blood-brain barrier with difficulties reaching the central nervous system to provide therapeutic effectiveness. To overcome this limitation, the nano-based drug delivery technology was used to synthesize melanin-like polydopamine nanoparticles (PDA NPs) (~ 250 nm) which can cross the blood-brain barrier. Importantly, PDA NPs with abundant phenolic hydroxyl groups function as excellent free radical scavengers to attenuate cell damage caused by reactive oxygen species or acute inflammation. In vitro experiments revealed that PDA NPs exhibited excellent antioxidative properties. Next, we aimed to investigate the therapeutic effect of PDA NPs on inflammatory depression through intraperitoneal injection to the lipopolysaccharide-induced inflammatory depression model in mice. PDA NPs significantly reversed the depression-like behavior. PDA NPs was also found to reduce the peripheral and central inflammation induced by LPS, showing that alleviated splenomegaly, reduced serum inflammatory cytokines, inhibited microglial activation and restored synaptic loss. Various experiments also showed that PDA NPs had good biocompatibility both in vivo and in vitro. Our work suggested that PDA NPs may be biocompatible nano-drugs in treating inflammatory depression but their clinical application requires further study.


Asunto(s)
Melaninas , Nanopartículas , Ratones , Animales , Depresión/tratamiento farmacológico , Nanopartículas/uso terapéutico , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Inflamación/tratamiento farmacológico
18.
Mol Neurobiol ; 60(6): 3210-3226, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36840846

RESUMEN

Accumulating evidence has suggested that a great proportion of sepsis survivors suffer from long-term cognitive impairments after hospital discharge, leading to decreased life quality and substantial caregiving burdens for family members. However, the underlying mechanism remains unclear. In the present study, we established a mouse model of systemic inflammation by repeated lipopolysaccharide (LPS) injections. A combination of behavioral tests, biochemical, and in vivo electrophysiology techniques were conducted to test whether abnormal NRG1/ErbB4 signaling, parvalbumin (PV) interneurons, and hippocampal neural oscillations were involved in memory decline after repeated LPS injections. Here, we showed that LPS induced long-term memory decline, which was accompanied by dysfunction of NRG1/ErbB4 signaling and PV interneurons, and decreased theta and gamma oscillations. Notably, NRG1 treatment reversed LPS-induced decreases in p-ErbB4 and PV expressions, abnormalities in theta and gamma oscillations, and long-term memory decline. Together, our study demonstrated that dysfunction of NRG1/ErbB4 signaling in the hippocampus might mediate long-term memory decline in a mouse model of systemic inflammation induced by repeated LPS injections. Thus, targeting NRG1/ErbB4 signaling in the hippocampus may be promising for the prevention and treatment of this long-term memory decline.


Asunto(s)
Lipopolisacáridos , Transducción de Señal , Ratones , Animales , Lipopolisacáridos/farmacología , Receptor ErbB-4/metabolismo , Interneuronas/metabolismo , Memoria a Largo Plazo , Inflamación/metabolismo , Hipocampo/metabolismo , Neurregulina-1/metabolismo , Parvalbúminas/metabolismo
19.
Phytomedicine ; 109: 154613, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36610112

RESUMEN

BACKGROUND: Small cell lung cancer (SCLC) is an aggressive tumor with high brain metastasis (BM) potential. There has been no significant progress in the treatment of SCLC for more than 30 years. Cordycepin has shown the therapeutic potential for cancer by modulating multiple cellular signaling pathways. However, the effect and mechanism of cordycepin on anti-SCLC BM remain unknown. PURPOSE: In this study, we focused on the anti-SCLC BM effect of cordycepin in the zebrafish model and its potential mechanism. STUDY DESIGN AND METHODS: A SCLC xenograft model based on zebrafish embryos and in vitro cell migration assay were established. Cordycepin was administrated by soaking and microinjection in the zebrafish model. RNA-seq assay was performed to analyze transcriptomes of different groups. Geno Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment were performed to reveal the underlying mechanism. Real-time qPCR was used to verify the effects of cordycepin on the key genes. RESULTS: Cordycepin showed lower cytotoxicity in vitro compared with cisplatin, anlotinib and etoposide, but showed comparable anti-proliferation and anti-BM effects in zebrafish SCLC xenograft model. Cordycepin showed significant anti-SCLC BM effects when administrated by both soaking and microinjection. RNA-seq demonstrated that cordycepin was involved in vitamin D metabolism, lipid transport, and proteolysis in cellular protein catabolic process pathways in SCLC BM microenvironment in zebrafish, and was involved in regulating the expressions of key genes such as cyp24a1, apoa1a, ctsl. The anti-BM effect of cordycepin in SCLC was mediated by reversing the expression of these genes. CONCLUSION: Our work is the first to describe the mechanism of cordycepin against SCLC BM from the perspective of regulating the brain microenvironment, providing new evidence for the anti-tumor effect of cordycepin.


Asunto(s)
Neoplasias Encefálicas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células Pequeñas , Animales , Humanos , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico , Carcinoma Pulmonar de Células Pequeñas/genética , Carcinoma Pulmonar de Células Pequeñas/patología , Pez Cebra , Neoplasias Pulmonares/patología , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/patología , Línea Celular Tumoral , Microambiente Tumoral
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