Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 233
Filtrar
1.
Front Pharmacol ; 15: 1426769, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39253375

RESUMEN

Depression, a mood disorder characterized by a persistent low mood and lack of enjoyment, is considered the leading cause of non-fatal health losses worldwide. Neuroplasticity refers to the brain's ability to adapt to external or internal stimuli, resulting in functional and structural changes. This process plays a crucial role in the development of depression. Traditional Chinese Medicine (TCM) shows significant potential as a complementary and alternative therapy for neurological diseases, including depression. However, there has been no systematic summary of the role of neuroplasticity in the pathological development of depression and TCM Interventions currently. This review systematically summarized recent literature on changes in neuroplasticity in depression and analyzed the regulatory mechanisms of active metabolites in TCM and TCM formulas on neuroplasticity in antidepressant treatment. Additionally, this review discussed the limitations of current research and the application prospects of TCM in regulating neuroplasticity in antidepressant research.

2.
Pharmacol Res ; 208: 107410, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39276955

RESUMEN

Histone deacetylases (HDACs) are zinc-dependent deacetylases that remove acetyl groups from lysine residues of histones or form protein complexes with other proteins for transcriptional repression, changing chromatin structure tightness, and inhibiting gene expression. Recent in vivo and in vitro studies have amply demonstrated the critical role of HDACs in the cell biology of the nervous system during both physiological and pathological processes and have provided new insights into the conduct of research on neurological disease targets. In addition, in vitro and in vivo studies on HDAC inhibitors show promise for the treatment of various diseases. This review summarizes the regulatory mechanisms of HDAC and the important role of its downstream targets in nervous system diseases, and summarizes the therapeutic mechanisms and efficacy of HDAC inhibitors in various nervous system diseases. Additionally, the current pharmacological situation, problems, and developmental prospects of HDAC inhibitors are described. A better understanding of the pathogenic mechanisms of HDACs in the nervous system may reveal new targets for therapeutic interventions in diseases and help to relieve healthcare pressure through preventive measures.


Asunto(s)
Inhibidores de Histona Desacetilasas , Histona Desacetilasas , Enfermedades del Sistema Nervioso , Humanos , Inhibidores de Histona Desacetilasas/uso terapéutico , Inhibidores de Histona Desacetilasas/farmacología , Animales , Histona Desacetilasas/metabolismo , Enfermedades del Sistema Nervioso/tratamiento farmacológico , Enfermedades del Sistema Nervioso/enzimología
3.
Int J Mol Sci ; 25(17)2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39273222

RESUMEN

Tea plants are a perennial crop with significant economic value. Chlorophyll, a key factor in tea leaf color and photosynthetic efficiency, is affected by the photoperiod and usually exhibits diurnal and seasonal variations. In this study, high-throughput transcriptomic analysis was used to study the chlorophyll metabolism, under different photoperiods, of tea plants. We conducted a time-series sampling under a skeleton photoperiod (6L6D) and continuous light conditions (24 L), measuring the chlorophyll and carotenoid content at a photoperiod interval of 3 h (24 h). Transcriptome sequencing was performed at six time points across two light cycles, followed by bioinformatics analysis to identify and annotate the differentially expressed genes (DEGs) involved in chlorophyll metabolism. The results revealed distinct expression patterns of key genes in the chlorophyll biosynthetic pathway. The expression levels of CHLE (magnesium-protoporphyrin IX monomethyl ester cyclase gene), CHLP (geranylgeranyl reductase gene), CLH (chlorophyllase gene), and POR (cytochrome P450 oxidoreductase gene), encoding enzymes in chlorophyll synthesis, were increased under continuous light conditions (24 L). At 6L6D, the expression levels of CHLP1.1, POR1.1, and POR1.2 showed an oscillating trend. The expression levels of CHLP1.2 and CLH1.1 showed the same trend, they both decreased under light treatment and increased under dark treatment. Our findings provide potential insights into the molecular basis of how photoperiods regulate chlorophyll metabolism in tea plants.


Asunto(s)
Clorofila , Ritmo Circadiano , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Fotoperiodo , Transcriptoma , Clorofila/metabolismo , Ritmo Circadiano/genética , Camellia sinensis/genética , Camellia sinensis/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Secuenciación de Nucleótidos de Alto Rendimiento
4.
Phytomedicine ; 134: 156012, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39260135

RESUMEN

BACKGROUND: Major depressive disorder (MDD) is a severe mental health condition characterized by persistent depression, impaired cognition, and reduced activity. Increasing evidence suggests that gut microbiota (GM) imbalance is closely linked to the emergence and advancement of MDD, highlighting the potential significance of regulating the "Microbiota-Gut-Brain" (MGB) axis to impact the development of MDD. Natural products (NPs), characterized by broad biological activities, low toxicity, and multi-target characteristics, offer unique advantages in antidepressant treatment by regulating MGB axis. PURPOSE: This review was aimed to explore the intricate relationship between the GM and the brain, as well as host responses, and investigated the mechanisms underlying the MGB axis in MDD development. It also explored the pharmacological mechanisms by which NPs modulate MGB axis to exert antidepressant effects and addressed current research limitations. Additionally, it proposed new strategies for future preclinical and clinical applications in the MDD domain. METHODS: To study the effects and mechanism by which NPs exert antidepressant effects through mediating the MGB axis, data were collected from Web of Science, PubMed, ScienceDirect from initial establishment to March 2024. NPs were classified and summarized by their mechanisms of action. RESULTS: NPs, such as flavonoids,alkaloids,polysaccharides,saponins, terpenoids, can treat MDD by regulating the MGB axis. Its mechanism includes balancing GM, regulating metabolites and neurotransmitters such as SCAFs, 5-HT, BDNF, inhibiting neuroinflammation, improving neural plasticity, and increasing neurogenesis. CONCLUSIONS: NPs display good antidepressant effects, and have potential value for clinical application in the prevention and treatment of MDD by regulating the MGB axis. However, in-depth study of the mechanisms by which antidepressant medications affect MGB axis will also require considerable effort in clinical and preclinical research, which is essential for the development of effective antidepressant treatments.


Asunto(s)
Antidepresivos , Productos Biológicos , Eje Cerebro-Intestino , Trastorno Depresivo Mayor , Microbioma Gastrointestinal , Antidepresivos/farmacología , Humanos , Microbioma Gastrointestinal/efectos de los fármacos , Eje Cerebro-Intestino/efectos de los fármacos , Eje Cerebro-Intestino/fisiología , Trastorno Depresivo Mayor/tratamiento farmacológico , Productos Biológicos/farmacología , Animales , Encéfalo/efectos de los fármacos
5.
Int J Biol Macromol ; 278(Pt 3): 134853, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39163955

RESUMEN

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Sepsis causes a high mortality rate and current treatment focuses on supportive therapies but lacks specific therapeutic targets. Notably, sirtuins (SIRTs) shows potential clinical application in the treatment of sepsis. It has been demonstrated that SIRTs, the nicotinamide adenine dinucleotide+(NAD+)-dependent deacetylases that regulate key signaling pathways in eukaryotes and prokaryotes, are involved in a variety of biological processes. To date, seven mammalian yeast Sir2 homologs have been identified. SIRTs can regulate inflammation, oxidative stress, apoptosis, autophagy, and other pathways that play important roles in sepsis-induced organ dysfunction. However, the existing studies on SIRTs in sepsis are too scattered, and there is no relevant literature to integrate them. This review innovatively summarizes the different mechanisms of SIRTs in sepsis organ dysfunction according to the different systems, and focuses on SIRT agonists, inhibitors, and targeted drugs that have been proved to be effective in the treatment of sepsis, so as to integrate the clinical research and basic research closely. We searched PubMed for all literature related to SIRTs and sepsis since its inception using the following medical subject headings: sirtuins, SIRTs, and sepsis. Data on the mechanisms of SIRTs in sepsis-induced organ damage and their potential as targets for disease treatment were extracted.


Asunto(s)
Insuficiencia Multiorgánica , Sepsis , Sirtuinas , Sirtuinas/metabolismo , Sepsis/metabolismo , Sepsis/complicaciones , Humanos , Animales , Insuficiencia Multiorgánica/etiología , Insuficiencia Multiorgánica/metabolismo , Estrés Oxidativo , Transducción de Señal
6.
Biomed Pharmacother ; 179: 117295, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39146765

RESUMEN

Despite considerable research efforts, inflammatory diseases remain a heavy burden on human health, causing significant economic losses annually. Histone deacetylases (HDACs) play a significant role in regulating inflammation (via histone and non-histone protein deacetylation) and chromatin structure and gene expression regulation. Herein, we present a detailed description of the different HDACs and their functions and analyze the role of HDACs in inflammatory diseases, including pro-inflammatory cytokine production reduction, immune cell function modulation, and anti-inflammatory cell activity enhancement. Although HDAC inhibitors have shown broad inflammatory disease treatment potentials, their clinical applicability remains limited because of their non-specific effects, adverse effects, and drug resistance. With further research and insight, these inhibitors are expected to become important tools for the treatment of a wide range of inflammatory diseases. This review aims to explore the mechanisms and application prospects of HDACs and their inhibitors in multiple inflammatory diseases.


Asunto(s)
Inhibidores de Histona Desacetilasas , Histona Desacetilasas , Inflamación , Inhibidores de Histona Desacetilasas/uso terapéutico , Inhibidores de Histona Desacetilasas/farmacología , Humanos , Histona Desacetilasas/metabolismo , Inflamación/tratamiento farmacológico , Animales , Antiinflamatorios/uso terapéutico , Antiinflamatorios/farmacología
7.
J Control Release ; 374: 230-241, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39151829

RESUMEN

The combination of therapy-induced immunogenic cell death (ICD) and immune checkpoint blockade can provide a mutually reinforced strategy to reverse the poor immunogenicity and immune escape behavior of tumors. In this work, a chimeric peptide-engineered immunostimulant (ER-PPB) is fabricated for endoplasmic reticulum (ER)-targeted photodynamic immunotherapy against metastatic tumors. Among which, the amphiphilic chimeric peptide (ER-PP) is composed of ER-targeting peptide FFKDEL, hydrophilic PEG8 linker and photosensitizer protoporphyrin IX (PpIX), which could be assembled with a PD-1/PD-L1 blocker (BMS-1) to prepare ER-PPB. After passively targeting at tumor tissues, ER-PPB will selectively accumulate in the ER. Next, the localized PDT of ER-PPB will produce a lot of ROS to destroy the primary tumor cells, while increasing the ER stress to initiate a robust ICD cascade. Moreover, the concomitant delivery of BMS-1 can impede the immune escape of tumor cells through PD-1/PD-L1 blockade, thus synergistically activating the immune system to combat metastatic tumors. In vitro and in vivo results demonstrate the robust immune activation and metastatic tumor inhibition characteristics of ER-PPB, which may offer a promising strategy for spatiotemporally controlled metastatic tumor therapy.


Asunto(s)
Retículo Endoplásmico , Inmunoterapia , Péptidos , Fotoquimioterapia , Fármacos Fotosensibilizantes , Protoporfirinas , Animales , Fotoquimioterapia/métodos , Inmunoterapia/métodos , Fármacos Fotosensibilizantes/administración & dosificación , Fármacos Fotosensibilizantes/uso terapéutico , Fármacos Fotosensibilizantes/farmacología , Línea Celular Tumoral , Péptidos/química , Péptidos/administración & dosificación , Protoporfirinas/administración & dosificación , Protoporfirinas/química , Humanos , Ratones , Adyuvantes Inmunológicos/administración & dosificación , Adyuvantes Inmunológicos/uso terapéutico , Adyuvantes Inmunológicos/farmacología , Femenino , Antígeno B7-H1/antagonistas & inhibidores , Antígeno B7-H1/inmunología , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/inmunología , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Neoplasias/terapia , Neoplasias/inmunología , Neoplasias/patología , Estrés del Retículo Endoplásmico/efectos de los fármacos
8.
Nat Commun ; 15(1): 6823, 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39122704

RESUMEN

Current treatments for chronic diarrhea have limited efficacy and several side effects. Probiotics have the potential to alleviate symptoms of diarrhea. This randomized, double-blind, placebo-controlled trial evaluates the effects of administering the probiotic Lactiplantibacillus plantarum P9 (P9) strain in young adults with chronic diarrhea (Clinical Trial Registration Number: ChiCTR2000038410). The intervention period lasts for 28 days, followed by a 14-day post-intervention period. Participants are randomized into the P9 (n = 93) and placebo (n = 96) groups, with 170 individuals completing the double-blind intervention phase (n = 85 per group). The primary endpoint is the diarrhea symptom severity score. Both intention-to-treat (n = 189) and per-protocol (n = 170) analyses reveal a modest yet statistically significant reduction in diarrhea severity compared to the placebo group (20.0%, P = 0.050; 21.4%, P = 0.048, respectively). In conclusion, the results of this study support the use of probiotics in managing chronic diarrhea in young adults. However, the lack of blood parameter assessment and the short intervention period represent limitations of this study.


Asunto(s)
Diarrea , Probióticos , Humanos , Diarrea/microbiología , Diarrea/terapia , Probióticos/uso terapéutico , Probióticos/administración & dosificación , Método Doble Ciego , Masculino , Adulto Joven , Adulto , Femenino , Enfermedad Crónica , Resultado del Tratamiento , Lactobacillus plantarum , Adolescente
9.
Adv Mater ; : e2404923, 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-39149776

RESUMEN

Epitaxial growth of 2D transition metal dichalcogenides (TMDCs) on sapphire substrates has been recognized as a pivotal method for producing wafer-scale single-crystal films. Both step-edges and symmetry of substrate surfaces have been proposed as controlling factors. However, the underlying fundamental still remains elusive. In this work, through the molybdenum disulfide (MoS2) growth on C/M sapphire, it is demonstrated that controlling the sulfur evaporation rate is crucial for dictating the switch between atomic-edge guided epitaxy and van der Waals epitaxy. Low-concentration sulfur condition preserves O/Al-terminated step edges, fostering atomic-edge epitaxy, while high-concentration sulfur leads to S-terminated edges, preferring van der Waals epitaxy. These experiments reveal that on a 2 in. wafer, the van der Waals epitaxy mechanism achieves better control in MoS2 alignment (≈99%) compared to the step edge mechanism (<85%). These findings shed light on the nuanced role of atomic-level thermodynamics in controlling nucleation modes of TMDCs, thereby providing a pathway for the precise fabrication of single-crystal 2D materials on a wafer scale.

10.
Mol Med ; 30(1): 113, 2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39095693

RESUMEN

BACKGROUND: To explore whether nobiletin has a protective effect on high-fat diet (HFD)-induced enteric nerve injury and its underlying mechanism. METHODS: An obesity model was induced by a HFD. Nobiletin (100 mg/kg and 200 mg/kg) and vehicle were administered by gastric gavage for 4 weeks. Lee's index, body weight, OGTT and intestinal propulsion assays were performed before sacrifice. After sampling, lipids were detected using Bodipy 493/503; lipid peroxidation was detected using MDA and SOD kits and the expression of PGP 9.5, Trem2, GFAP, ß-tubulin 3, Bax, Bcl2, Nestin, P75 NTR, SOX10 and EDU was detected using immunofluorescence. The GDNF, p-AKT, AKT, p-FOXO3a, FOXO3a and P21 proteins were detected using western blotting. The relative mRNA expression levels of NOS2 were detected via qPCR. Primary enteric neural stem cells (ENSCs) were cultured. After ENSCs were treated with palmitic acid (PA) and nobiletin, CCK-8 and caspase-3/7 activity assays were performed to evaluate proliferation and apoptosis. RESULTS: HFD consumption caused colon lipid accumulation and peroxidation, induced enteric nerve damage and caused intestinal motor dysfunction. However, nobiletin reduced lipid accumulation and peroxidation in the colon; promoted Trem2, ß-tubulin 3, Nestin, P75NTR, SOX10 and Bcl2 expression; inhibited Bax and GFAP expression; reduced NOS2 mRNA transcription; and regulated the GDNF/AKT/FOXO3a/P21 pathway. Nobiletin also promoted PA-induced impairment of ENSCs. CONCLUSIONS: Nobiletin restored HFD-induced enteric nerve injury, which may be associated with inhibiting enteric nerve apoptosis, promoting enteric nerve survival and regulating the GDNF/AKT/FOXO3a/P21 pathway.


Asunto(s)
Dieta Alta en Grasa , Sistema Nervioso Entérico , Flavonas , Proteína Forkhead Box O3 , Factor Neurotrófico Derivado de la Línea Celular Glial , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Animales , Proteína Forkhead Box O3/metabolismo , Factor Neurotrófico Derivado de la Línea Celular Glial/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Dieta Alta en Grasa/efectos adversos , Transducción de Señal/efectos de los fármacos , Masculino , Flavonas/farmacología , Flavonas/uso terapéutico , Sistema Nervioso Entérico/metabolismo , Sistema Nervioso Entérico/efectos de los fármacos , Neuroglía/metabolismo , Neuroglía/efectos de los fármacos , Ratones , Modelos Animales de Enfermedad , Ratas , Obesidad/metabolismo , Obesidad/tratamiento farmacológico , Apoptosis/efectos de los fármacos
11.
World J Gastrointest Endosc ; 16(8): 483-488, 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-39155996

RESUMEN

BACKGROUND: Multisystem inflammatory syndrome in adults (MIS-A) is a rare but severe disease occurring several weeks after severe acute respiratory syndrome coronavirus 2 infection. It develops in adults with inflammation of different organs including the gastrointestinal tract, heart, kidneys, skin and hematopoietic system. CASE SUMMARY: We present a 58-year-old Chinese man diagnosed with MIS-A. His chief complaints were fever, generalized fatigue and anorexia, accompanied with rashes on his back. Further examination showed cardiac, renal and liver injury. He had melena and gastroscopy indicated esophageal ulcer and severe esophagitis. Repeated blood and sputum culture did not show growth of bacteria or fungi. Antibiotic treatment was stopped due to unsatisfactory performance. His condition improved after prednisone and other supportive treatment. CONCLUSION: Gastrointestinal involvement in MIS-A is not uncommon. Intestinal involvement predominates, and esophageal involvement is rarely reported. Esophageal ulcer with bleeding could also be a manifestation of MIS-A.

12.
Exp Gerontol ; 195: 112538, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39116956

RESUMEN

Amyotrophic lateral sclerosis as a fatal neurodegenerative disease currently lacks effective therapeutic agents. Thus, finding new therapeutic targets to drive disease treatment is necessary. In this study, we utilized brain and plasma proteins as genetic instruments obtained from genome-wide association studies to conduct a Mendelian randomization analysis to identify potential drug targets for amyotrophic lateral sclerosis. Additionally, we validated our results externally using other datasets. We also used Bayesian co-localization analysis and phenotype scanning. Furthermore, we constructed a protein-protein interaction network to elucidate potential correlations between the identified proteins and existing targets. Mendelian randomization analysis indicated that elevated levels of ANO5 (OR = 1.30; 95 % CI, 1.14-1.49; P = 1.52E-04), SCFD1 (OR = 3.82; 95 % CI, 2.39-6.10; P = 2.19E-08), and SIGLEC9 (OR = 1.05; 95% CI, 1.03-1.07; P = 4.71E-05) are associated with an increased risk of amyotrophic lateral sclerosis, with external validation supporting these findings. Co-localization analysis confirmed that ANO5, SCFD1, and SIGLEC9 (coloc.abf-PPH4 = 0.848, 0.984, and 0.945, respectively) shared the same variant with amyotrophic lateral sclerosis, further substantiating potential role of these proteins as a therapeutic target. There are interactive relationships between the potential proteins and existing targets of amyotrophic lateral sclerosis. Our findings suggested that elevated levels of ANO5, SCFD1, and SIGLEC9 are connected with an increased risk of amyotrophic lateral sclerosis and might be promising therapeutic targets. However, further exploration is necessary to fully understand the underlying mechanisms involved.


Asunto(s)
Esclerosis Amiotrófica Lateral , Encéfalo , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Mapas de Interacción de Proteínas , Proteómica , Humanos , Esclerosis Amiotrófica Lateral/genética , Esclerosis Amiotrófica Lateral/sangre , Esclerosis Amiotrófica Lateral/tratamiento farmacológico , Proteómica/métodos , Encéfalo/metabolismo , Anoctaminas/genética , Teorema de Bayes , Proteínas Sanguíneas/análisis , Proteínas Sanguíneas/metabolismo , Predisposición Genética a la Enfermedad
13.
Free Radic Biol Med ; 223: 493-505, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39048340

RESUMEN

Increasing evidence underscores the pivotal role of ferroptosis in Parkinson's Disease (PD) pathogenesis. Acteoside (ACT) has been reported to possess neuroprotective properties. However, the effects of ACT on ferroptosis and its molecular mechanisms remain unknown. This study aimed to explore whether ACT can regulate ferroptosis in dopaminergic (DA) neurons within both in vitro and in vivo PD models and to elucidate the underlying regulatory mechanisms. PD models were established and treated with various concentrations of ACT. Cell viability assays, Western blot, lipid peroxidation assessments, immunohistochemistry, and transmission electron microscopy were employed to confirm ACT's inhibition of ferroptosis and its protective effect on DA neurons across PD models. Immunofluorescence staining, MitoSOX staining, and confocal laser scanning microscopy further validated ACT's regulation regulatory effects on ferroptosis via the Nrf2-mitophagy pathway. Four animal behavioral tests were used to assess behavioral improvements in PD animals. ACT inhibited ferroptosis in PD models in vitro, as evidenced by increased cell viability, the upregulation of GPX4 and SLC7A11, reduced lipid peroxides, and attenuation of mitochondrial morphological alterations typical of ferroptosis. By activating the Nrf2-mitophagy axis, ACT enhanced mitochondrial integrity and reduced lipid peroxidation, mitigating ferroptosis. These in vitro results were consistent with in vivo findings, where ACT treatment significantly preserved DA neurons, curbed ferroptosis in these cells, and alleviated cognitive and behavioral deficits. This study is the first demonstration of ACT's capability to inhibit neuronal ferroptosis and protect DA neurons, thus alleviating behavioral and cognitive impairments in both in vitro and in vivo PD models. Furthermore, The suppression of ferroptosis by ACT is achieved through the activation of the Nrf2-mitophagy signaling pathway. Our results show that ACT is beneficial for both treating and preventing PD. They also offer novel therapeutic options for treating PD and molecular targets for regulating ferroptosis.


Asunto(s)
Neuronas Dopaminérgicas , Ferroptosis , Glucósidos , Peroxidación de Lípido , Mitofagia , Factor 2 Relacionado con NF-E2 , Fármacos Neuroprotectores , Enfermedad de Parkinson , Fenoles , Ferroptosis/efectos de los fármacos , Factor 2 Relacionado con NF-E2/metabolismo , Factor 2 Relacionado con NF-E2/genética , Animales , Peroxidación de Lípido/efectos de los fármacos , Glucósidos/farmacología , Ratones , Enfermedad de Parkinson/metabolismo , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/patología , Neuronas Dopaminérgicas/metabolismo , Neuronas Dopaminérgicas/efectos de los fármacos , Neuronas Dopaminérgicas/patología , Fármacos Neuroprotectores/farmacología , Mitofagia/efectos de los fármacos , Fenoles/farmacología , Masculino , Modelos Animales de Enfermedad , Humanos , Supervivencia Celular/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Neuroprotección/efectos de los fármacos , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismo , Fosfolípido Hidroperóxido Glutatión Peroxidasa/genética , Polifenoles
14.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(7): 774-781, 2024 Jul 15.
Artículo en Chino | MEDLINE | ID: mdl-39014956

RESUMEN

Sepsis-induced myocardial depression (SIMD), a common complication of sepsis, is one of the main causes of death in patients with sepsis. The pathogenesis of SIMD is complicated, and the process of SIMD remains incompletely understood, with no single or definitive mechanism fully elucidated. Notably, pyroptosis, as a pro-inflammatory programmed cell death, is characterized by Gasdermin-mediated formation of pores on the cell membrane, cell swelling, and cell rupture accompanied by the release of large amounts of inflammatory factors and other cellular contents. Mechanistically, pyroptosis is mainly divided into the canonical pathway mediated by caspase-1 and the non-canonical pathway mediated by caspase-4/5/11. Pyroptosis has been confirmed to participate in various inflammation-associated diseases. In recent years, more and more studies have shown that pyroptosis is also involved in the occurrence and development of SIMD. This article reviews the molecular mechanisms of pyroptosis and its research progress in SIMD, aiming to provide novel strategies and targets for the treatment of SIMD.


Asunto(s)
Piroptosis , Sepsis , Humanos , Sepsis/complicaciones , Animales , Cardiomiopatías/etiología
15.
Front Psychiatry ; 15: 1335554, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38957739

RESUMEN

Background: Mobile phone addiction (MPA) greatly affects the biological clock and sleep quality and is emerging as a behavioral disorder. The saliva microbiota has been linked to circadian rhythms, and our previous research revealed dysrhythmic saliva metabolites in MPA subjects with sleep disorders (MPASD). In addition, acupuncture had positive effects. However, the dysbiotic saliva microbiota in MPASD patients and the restorative effects of acupuncture are unclear. Objectives: To probe the circadian dysrhythmic characteristics of the saliva microbiota and acupunctural restoration in MPASD patients. Methods: MPASD patients and healthy volunteers were recruited by the Mobile Phone Addiction Tendency Scale (MPATS) and the Pittsburgh Sleep Quality Index (PSQI). Saliva samples were collected every 4 h for 72 h. After saliva sampling, six MPDSD subjects (group M) were acupuncturally treated (group T), and subsequent saliva sampling was conducted posttreatment. Finally, all the samples were subjected to 16S rRNA gene sequencing and bioinformatic analysis. Results: Significantly increased MPATS and PSQI scores were observed in MPDSD patients (p< 0.01), but these scores decreased (p<0.001) after acupuncture intervention. Compared with those in healthy controls, the diversity and structure of the saliva microbiota in MPASD patients were markedly disrupted. Six genera with circadian rhythms were detected in all groups, including Sulfurovum, Peptostreptococcus, Porphyromonas and Prevotella. There were five genera with circadian rhythmicity in healthy people, of which the rhythmicities of the genera Rothia and Lautropia disappeared in MPASD patients but effectively resumed after acupuncture intervention. Conclusions: This work revealed dysrhythmic salivary microbes in MPASD patients, and acupuncture, as a potential intervention, could be effective in mitigating this ever-rising behavioral epidemic.

16.
Molecules ; 29(14)2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39064904

RESUMEN

Carrier-free self-assembly has gradually shifted the focus of research on natural products, which effectively improve the bioavailability and the drug-loading rate. However, in spite of the existing studies, the development of self-assembled natural phytochemicals that possess pharmacological effects still has scope for further exploration and enhancement. Herein, a nano-delivery system was fabricated through the direct self-assembly of Rhein and Matrine and was identified as a self-assembled Rhein-Matrine nanoparticles (RM NPs). The morphology of RM NPs was characterized by TEM. The molecular mechanisms of self-assembly were explored using FT-IR, 1H NMR, and molecular dynamics simulation analysis. Gelatin methacryloyl (GelMA) hydrogel was used as a drug carrier for controlled release and targeted delivery of RM NPs. The potential wound repair properties of RM NPs were evaluated on a skin wound-healing model. TEM and dynamic light scattering study demonstrated that the RM NPs were close to spherical, and the average size was approximately 75 nm. 1H NMR of RM NPs demonstrated strong and weak changes in the interaction energies during self-assembly. Further molecular dynamics simulation analysis predicted the self-assembly behavior. An in vivo skin wound-healing model demonstrated that RM NPs present better protection effect against skin damages. Taken together, RM NPs are a new self-assembly system; this may provide new directions for natural product applications.


Asunto(s)
Alcaloides , Antraquinonas , Matrinas , Simulación de Dinámica Molecular , Nanopartículas , Quinolizinas , Cicatrización de Heridas , Alcaloides/química , Alcaloides/farmacología , Cicatrización de Heridas/efectos de los fármacos , Quinolizinas/química , Quinolizinas/farmacología , Nanopartículas/química , Antraquinonas/química , Antraquinonas/farmacología , Animales , Portadores de Fármacos/química , Ratones , Hidrogeles/química , Humanos
17.
Nano Lett ; 24(28): 8525-8534, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-38954769

RESUMEN

Cr2(NCN)3 is a potentially high-capacity and fast-charge Li-ion anode owing to its abundant and broad tunnels. However, high intrinsic chemical instability severely restricts its capacity output and electrochemical reversibility. Herein we report an effective crystalline engineering method for optimizing its phase and crystallinity. Systematic studies reveal the relevancy between electrochemical performance and crystalline structure; an optimal Cr2(NCN)3 with high phase purity and uniform crystallinity exhibits a high reversible capacity of 590 mAh g-1 and a stable cycling performance of 478 mAh g-1 after 500 cycles. In-operando heating XRD reveals its high thermodynamical stability over 600 °C, and in-operando electrochemical XRD proves its electrochemical Li storage mechanism, consisting of the primary Li-ion intercalation and subsequent conversion reactions. This study introduces a facile and low-cost method for fabricating high-purity Cr2(NCN)3, and it also confirms that the Li storage of Cr2(NCN)3 can be further improved by tuning its phase and crystallinity.

18.
J Chromatogr A ; 1730: 465118, 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-38936162

RESUMEN

Terpenoids possess significant physiological activities and are rich in essential oils. Some terpenoids have chiral centers and could form enantiomers with distinct physiological activities. Therefore, the extraction and separation of terpenoids enantiomers are very important and have attracted extensive attention in recent years. Meanwhile, the specific distribution and enantiomer excess results (the excess of one enantiomer over the other in a mixture of enantiomers) could be used as quality markers for illegitimate adulteration, origin identification, and exploring component variations and functional interrelations across different plant tissues. In this study, an overview of the progress in the extraction of terpenoids from essential oils and the separation of their enantiomers over the past two decades has been made. Extraction methods were retrieved by the resultant network visualization findings. The results showed that the predominant methods are hydrodistillation, solvent-free microwave extraction, headspace solid-phase microextraction and supercritical fluid extraction methods. GC-MS combined with chiral chromatography columns is commonly used for the separation of enantiomers, while 2D GC is found to have stronger resolution ability. Finally, some prospects for future research directions in the extraction and separation identification of essential oils are proposed.


Asunto(s)
Cromatografía de Gases y Espectrometría de Masas , Aceites Volátiles , Terpenos , Aceites Volátiles/química , Aceites Volátiles/aislamiento & purificación , Aceites Volátiles/análisis , Terpenos/química , Terpenos/aislamiento & purificación , Terpenos/análisis , Cromatografía de Gases y Espectrometría de Masas/métodos , Estereoisomerismo , Cromatografía con Fluido Supercrítico/métodos , Microextracción en Fase Sólida/métodos
19.
Front Neurol ; 15: 1380321, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38725646

RESUMEN

Introduction: Insomnia, a common clinical disorder, significantly impacts the physical and mental well-being of patients. Currently, available hypnotic medications are unsatisfactory due to adverse reactions and dependency, necessitating the identification of new drug targets for the treatment of insomnia. Methods: In this study, we utilized 734 plasma proteins as genetic instruments obtained from genome-wide association studies to conduct a Mendelian randomization analysis, with insomnia as the outcome variable, to identify potential drug targets for insomnia. Additionally, we validated our results externally using other datasets. Sensitivity analyses entailed reverse Mendelian randomization analysis, Bayesian co-localization analysis, and phenotype scanning. Furthermore, we constructed a protein-protein interaction network to elucidate potential correlations between the identified proteins and existing targets. Results: Mendelian randomization analysis indicated that elevated levels of TGFBI (OR = 1.01; 95% CI, 1.01-1.02) and PAM ((OR = 1.01; 95% CI, 1.01-1.02) in plasma are associated with an increased risk of insomnia, with external validation supporting these findings. Moreover, there was no evidence of reverse causality for these two proteins. Co-localization analysis confirmed that PAM (coloc.abf-PPH4 = 0.823) shared the same variant with insomnia, further substantiating its potential role as a therapeutic target. There are interactive relationships between the potential proteins and existing targets of insomnia. Conclusion: Overall, our findings suggested that elevated plasma levels of TGFBI and PAM are connected with an increased risk of insomnia and might be promising therapeutic targets, particularly PAM. However, further exploration is necessary to fully understand the underlying mechanisms involved.

20.
BMC Plant Biol ; 24(1): 333, 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38664694

RESUMEN

BACKGROUND: The circadian clock, also known as the circadian rhythm, is responsible for predicting daily and seasonal changes in the environment, and adjusting various physiological and developmental processes to the appropriate times during plant growth and development. The circadian clock controls the expression of the Lhcb gene, which encodes the chlorophyll a/b binding protein. However, the roles of the Lhcb gene in tea plant remain unclear. RESULTS: In this study, a total of 16 CsLhcb genes were identified based on the tea plant genome, which were distributed on 8 chromosomes of the tea plant. The promoter regions of CsLhcb genes have a variety of cis-acting elements including hormonal, abiotic stress responses and light response elements. The CsLhcb family genes are involved in the light response process in tea plant. The photosynthetic parameter of tea leaves showed rhythmic changes during the two photoperiod periods (48 h). Stomata are basically open during the day and closed at night. Real-time quantitative PCR results showed that most of the CsLhcb family genes were highly expressed during the day, but were less expressed at night. CONCLUSIONS: Results indicated that CsLhcb genes were involved in the circadian clock process of tea plant, it also provided potential references for further understanding of the function of CsLhcb gene family in tea plant.


Asunto(s)
Camellia sinensis , Ritmo Circadiano , Fotosíntesis , Fotosíntesis/genética , Camellia sinensis/genética , Camellia sinensis/fisiología , Ritmo Circadiano/genética , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Genes de Plantas , Familia de Multigenes , Proteínas de Unión a Clorofila/genética , Proteínas de Unión a Clorofila/metabolismo , Fotoperiodo
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA