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1.
PLoS Genet ; 18(12): e1010545, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36512630

RESUMEN

Replication fork reversal which restrains DNA replication progression is an important protective mechanism in response to replication stress. PARP1 is recruited to stalled forks to restrain DNA replication. However, PARP1 has no helicase activity, and the mechanism through which PARP1 participates in DNA replication restraint remains unclear. Here, we found novel protein-protein interactions between PARP1 and DNA translocases, including HLTF, SHPRH, ZRANB3, and SMARCAL1, with HLTF showing the strongest interaction among these DNA translocases. Although HLTF and SHPRH share structural and functional similarity, it remains unclear whether SHPRH contains DNA translocase activity. We further identified the ability of SHPRH to restrain DNA replication upon replication stress, indicating that SHPRH itself could be a DNA translocase or a helper to facilitate DNA translocation. Although hydroxyurea (HU) and MMS induce different types of replication stress, they both induce common DNA replication restraint mechanisms independent of intra-S phase activation. Our results suggest that the PARP1 facilitates DNA translocase recruitment to damaged forks, preventing fork collapse and facilitating DNA repair.


Asunto(s)
Proteínas de Unión al ADN , Factores de Transcripción , Proteínas de Unión al ADN/genética , Factores de Transcripción/genética , Reparación del ADN/genética , Replicación del ADN/genética , ADN/genética , Daño del ADN/genética
2.
J Am Chem Soc ; 146(26): 17924-17930, 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38900921

RESUMEN

Nitroalkanes serve as essential intermediates in the synthesis of pharmaceuticals, agrochemicals, and functional materials. To date, nitroalkanes are mainly prepared from homogeneous catalysts such as noble transition metal catalysts with poor recyclability. Herein, we propose a metal-organic framework-frustrated Lewis pair (MOF-FLP) heterogeneous catalyst for selectively reducing nitroolefins to nitroalkanes under moderate reaction conditions. MOF enrichment effect can significantly improve the catalytic efficiency compared to homogeneous FLP catalysts. Benefiting from the strong interaction between FLP and MOF, the MOF-FLP catalyst exhibits outstanding recyclability. This work not only provides a convenient route for nitroalkane synthesis but also showcases the potential of porous heterogeneous FLP catalysts, offering inspiration for future catalytic design strategies.

3.
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
4.
Drug Metab Rev ; 56(1): 62-79, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38226647

RESUMEN

Melatonin, historically recognized for its primary role in regulating circadian rhythms, has expanded its influence particularly due to its wide range of biological activities. It has firmly established itself in cancer research. To highlight its versatility, we delved into how melatonin interacts with key signaling pathways, such as the Wnt/ß-Catenin, PI3K, and NF-κB pathways, which play foundational roles in tumor development and progression. Notably, melatonin can intricately modulate these pathways, potentially affecting various cellular functions such as apoptosis, metastasis, and immunity. Additionally, a comprehensive review of current clinical studies provides a dual perspective. These studies confirm melatonin's potential in cancer management but also underscore its inherent limitations, particularly its limited bioavailability, which often relegates it to a supplementary role in treatments. Despite this limitation, there is an ongoing quest for innovative solutions and current advancements include the development of melatonin derivatives and cutting-edge delivery systems. By synthesizing the past, present, and future, this review provides a detailed overview of melatonin's evolving role in oncology, positioning it as a potential cornerstone in future cancer therapeutics.


Asunto(s)
Melatonina , Neoplasias , Humanos , Melatonina/uso terapéutico , Melatonina/metabolismo , Transducción de Señal , Biología , Neoplasias/tratamiento farmacológico
5.
Plant Cell Environ ; 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39262218

RESUMEN

Nicotiana benthamiana, a widely acknowledged laboratory model plant for molecular studies, exhibits lethality to certain insect pests and can serve as a dead-end trap plant for pest control in the field. However, the underlying mechanism of N. benthamiana's resistance against insects remains unknown. Here, we elucidate that the lethal effect of N. benthamiana on the whitefly Bemisia tabaci arises from the toxic glandular trichome exudates. By comparing the metabolite profiles of trichome exudates, we found that 51 metabolites, including five O-acyl sugars (O-AS) with medium-chain acyl moieties, were highly accumulated in N. benthamiana. Silencing of two O-AS biosynthesis genes, branched-chain keto acid dehydrogenase (BCKD) and Isopropyl malate synthase-C (IPMS-C), significantly reduced the O-AS levels in N. benthamiana and its resistance against whiteflies. Additionally, we demonstrated that the higher expression levels of BCKD and IPMS-C in the trichomes of N. benthamiana contribute to O-AS synthesis and consequently enhance whitefly resistance. Furthermore, overexpression of NbBCKD and NbIPMS-C genes in the cultivated tobacco Nicotiana tabacum enhanced its resistance to whiteflies. Our study revealed the metabolic and molecular mechanisms underlying the lethal effect of N. benthamiana on whiteflies and presents a promising avenue for improving whitefly resistance.

6.
Psychol Med ; 54(10): 2658-2668, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38563283

RESUMEN

BACKGROUND: The comorbidity between schizophrenia (SCZ) and inflammatory bowel disease (IBD) observed in epidemiological studies is partially attributed to genetic overlap, but the magnitude of shared genetic components and the causality relationship between them remains unclear. METHODS: By leveraging large-scale genome-wide association study (GWAS) summary statistics for SCZ, IBD, ulcerative colitis (UC), and Crohn's disease (CD), we conducted a comprehensive genetic pleiotropic analysis to uncover shared loci, genes, or biological processes between SCZ and each of IBD, UC, and CD, independently. Univariable and multivariable Mendelian randomization (MR) analyses were applied to assess the causality across these two disorders. RESULTS: SCZ genetically correlated with IBD (rg = 0.14, p = 3.65 × 10−9), UC (rg = 0.15, p = 4.88 × 10−8), and CD (rg = 0.12, p = 2.27 × 10−6), all surpassed the Bonferroni correction. Cross-trait meta-analysis identified 64, 52, and 66 significantly independent loci associated with SCZ and IBD, UC, and CD, respectively. Follow-up gene-based analysis found 11 novel pleiotropic genes (KAT5, RABEP1, ELP5, CSNK1G1, etc) in all joint phenotypes. Co-expression and pathway enrichment analysis illustrated those novel genes were mainly involved in core immune-related signal transduction and cerebral disorder-related pathways. In univariable MR, genetic predisposition to SCZ was associated with an increased risk of IBD (OR 1.11, 95% CI 1.07­1.15, p = 1.85 × 10−6). Multivariable MR indicated a causal effect of genetic liability to SCZ on IBD risk independent of Actinobacteria (OR 1.11, 95% CI 1.06­1.16, p = 1.34 × 10−6) or BMI (OR 1.11, 95% CI 1.04­1.18, p = 1.84 × 10−3). CONCLUSIONS: We confirmed a shared genetic basis, pleiotropic loci/genes, and causal relationship between SCZ and IBD, providing novel insights into the biological mechanism and therapeutic targets underlying these two disorders.


Asunto(s)
Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Enfermedades Inflamatorias del Intestino , Análisis de la Aleatorización Mendeliana , Esquizofrenia , Humanos , Esquizofrenia/genética , Enfermedades Inflamatorias del Intestino/genética , Colitis Ulcerosa/genética , Enfermedad de Crohn/genética , Enfermedad de Crohn/epidemiología , Pleiotropía Genética , Causalidad , Comorbilidad
7.
Mol Psychiatry ; 28(6): 2266-2276, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36670198

RESUMEN

Ketamine, a commonly used general anesthetic, can produce rapid and sustained antidepressant effect. However, the efficacy and safety of the perioperative application of ketamine on postoperative depression remains uncertain. We performed a meta-analysis to determine the effect of perioperative intravenous administration of ketamine on postoperative depression. Randomized controlled trials comparing ketamine with placebo in patients were included. Primary outcome was postoperative depression scores. Secondary outcomes included postoperative visual analog scale (VAS) scores for pain and adverse effects associated with ketamine. Fifteen studies with 1697 patients receiving ketamine and 1462 controls were enrolled. Compared with the controls, the ketamine group showed a reduction in postoperative depression scores, by a standardized mean difference (SMD) of -0.97, 95% confidence interval [CI, -1.27, -0.66], P < 0.001, I2 = 72% on postoperative day (POD) 1; SMD-0.65, 95% CI [-1.12, -0.17], P < 0.001, I2 = 94% on POD 3; SMD-0.30, 95% CI [-0.45, -0.14], P < 0.001, I2 = 0% on POD 7; and SMD-0.25, 95% CI [-0.38, -0.11], P < 0.001, I2 = 59% over the long term. Ketamine reduced VAS pain scores on POD 1 (SMD-0.93, 95% CI [-1.58, -0.29], P = 0.005, I2 = 97%), but no significant difference was found between the two groups on PODs 3 and 7 or over the long term. However, ketamine administration distinctly increased the risk of adverse effects, including nausea and vomiting (risk ratio [RR] 1.40, 95% CI [1.12, 1.75], P = 0.003, I2 = 30%), headache (RR 2.47, 95% CI [1.41, 4.32], P = 0.002, I2 = 19%), hallucination (RR 15.35, 95% CI [6.24, 37.34], P < 0.001, I2 = 89%), and dizziness (RR 3.48, 95% CI [2.68, 4.50], P < 0.001, I2 = 89%) compared with the controls. In conclusion, perioperative application of ketamine reduces postoperative depression and pain scores with increased risk of adverse effects.


Asunto(s)
Trastorno Depresivo , Ketamina , Humanos , Ketamina/uso terapéutico , Depresión/tratamiento farmacológico , Antidepresivos/uso terapéutico , Trastorno Depresivo/tratamiento farmacológico , Dolor/tratamiento farmacológico , Dolor Postoperatorio/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto
8.
Langmuir ; 40(32): 16846-16854, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39094224

RESUMEN

Films of the discotic liquid crystalline hexabenzocoronene (HBC) derivative, HBC-1,3,5-Ph-C12, were prepared on the quartz substrate by the bar-coating method. Depending on the coating speed, regularly spaced stripes or continuous films were observed. In the former case, columns of the HBC derivatives align more along the stripes, which are perpendicular to the coating direction, whereas in the latter case, columns of the HBC derivatives in the film align more along the coating direction. These distinctive structures are confirmed via polarized optical microscopy (POM), polarized UV-vis spectroscopy, and grazing incidence small-angle X-ray scattering measurements.

9.
J Org Chem ; 89(11): 7770-7779, 2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38738957

RESUMEN

A visible-light-enabled photoredox radical cascade cyclization of 2-vinyl benzimidazole derivatives is developed. This chemistry is applicable to a wide range of N-aroyl 2-vinyl benzimidazoles as acceptors, and halo compounds, including alkyl halides, acyl chlorides and sulfonyl chlorides, as radical precursors. The Langlois reagent also serves as an effective partner in this photocatalytic oxidative cascade process. This protocol provides a robust alternative for rendering highly functionalized benzo[4,5]imidazo[1,2-b]isoquinolin-11(6H)-ones.

10.
Prev Med ; : 108147, 2024 Oct 03.
Artículo en Inglés | MEDLINE | ID: mdl-39368643

RESUMEN

OBJECTIVE: Gastrointestinal cancers are one of the most frequent cancer types and seriously threaten human life and health. Recent studies attribute the occurrence of gastrointestinal cancers to both genetic and environmental factors, yet the intrinsic etiology remains unclear. Mendelian randomization is a powerful well-established statistical method that is based on genome-wide association study (GWAS) to evaluate the causal relationship between exposures and outcomes. In the present study, we aimed to conduct a systematic review of Mendelian randomization studies investigating any causal risk factors for gastrointestinal cancers. METHODS: We systematically searched Mendelian randomization studies that addressed the associations of genetically predicted exposures with five main gastrointestinal cancers from September 2014 to March 2024, as well as testing the research quality and validity. RESULTS: Our findings suggested robust and consistent causal effects of body mass index (BMI), basal metabolic rate, fatty acids, total cholesterol, total bilirubin, insulin like growth factor-1, eosinophil counts, interleukin 2, alcohol consumption, coffee consumption, apolipoprotein B on colorectal cancer risks, BMI, waist circumference, low-density lipoprotein (LDL), total testosterone, smoking on gastric cancer risks, BMI, fasting insulin, LDL, waist circumference, visceral adipose tissue (VAT), immune cells, type 2 diabetes mellitus (T2DM) on pancreatic cancer risks, waist circumference, smoking, T2DM on esophageal adenocarcinoma risks, and VAT, ferritin, transferrin, alcohol consumption, hepatitis B virus infection, rheumatoid arthritis on liver cancer risks, respectively. CONCLUSION: Larger, well-designed Mendelian randomization studies are practical in determining the causal status of risk factors for diseases.

11.
Br J Nutr ; 131(11): 1873-1882, 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38343175

RESUMEN

Previous studies have revealed an association between dietary factors and atopic dermatitis (AD). To explore whether there was a causal relationship between diet and AD, we performed Mendelian randomisation (MR) analysis. The dataset of twenty-one dietary factors was obtained from UK Biobank. The dataset for AD was obtained from the publicly available FinnGen consortium. The main research method was the inverse-variance weighting method, which was supplemented by MR‒Egger, weighted median and weighted mode. In addition, sensitivity analysis was performed to ensure the accuracy of the results. The study revealed that beef intake (OR = 0·351; 95 % CI 0·145, 0·847; P = 0·020) and white bread intake (OR = 0·141; 95 % CI 0·030, 0·656; P = 0·012) may be protective factors against AD. There were no causal relationships between AD and any other dietary intake factors. Sensitivity analysis showed that our results were reliable, and no heterogeneity or pleiotropy was found. Therefore, we believe that beef intake may be associated with a reduced risk of AD. Although white bread was significant in the IVW analysis, there was large uncertainty in the results given the wide 95 % CI. Other factors were not associated with AD in this study.


Asunto(s)
Dermatitis Atópica , Dieta , Análisis de la Aleatorización Mendeliana , Dermatitis Atópica/genética , Dermatitis Atópica/etiología , Humanos , Factores de Riesgo , Pan , Carne Roja/efectos adversos , Bovinos , Reino Unido/epidemiología , Animales
12.
Fish Shellfish Immunol ; 154: 109877, 2024 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-39245185

RESUMEN

cAMP response element binding (CREB) protein 2 (CRTC2) is a transcriptional coactivator of CREB and plays an important role in the immune system. Thus far, the physiological roles of Crtc2 in teleost are still poorly understood. In this study, the crtc2 gene was identified and characterized from yellow catfish (Pelteobagrus fulvidraco; therefore, the gene is termed as pfcrtc2), and its evolutionary and molecular characteristics as well as potential immunity-related roles were investigated. Our results showed that the open reading frame of pfcrtc2 was 2346 bp in length, encoding a protein with 781 amino acids. Gene structure analysis revealed its existence of 14 exons and 13 introns. A phylogenetic analysis proved that the tree of crtc2 was clustered into five groups, exhibiting a similar evolutionary topology with species evolution. Multiple protein sequences alignment demonstrated high conservation of the crtc2 in various vertebrates with similar structure. Syntenic and gene structural comparisons further established that crtc2 was highly conserved, implying its similar roles in diverse vertebrates. Tissue distribution pattern detected by quantitative real-time PCR showed that the pfcrtc2 gene was almost expressed in all detected tissues except for eyes, with the highest expression levels in the gonad, indicating that Crtc2 may play important roles in various tissues. In addition, pfcrtc2 was transcribed at all developmental stages in yellow catfish, showing the highest expression levels at 12 h after fertilization. Finally, the transcriptional profiles of crtc2 were significantly increased in yellow catfishes injected with Aeromonas hydrophila or Poly I:C, which shared a consistent change pattern with four immune-related genes including IL-17A, IL-10, MAPKp38, and NF-κBp65, suggesting pfCrtc2 may play critical roles in preventing both exogenous bacteria and virus invasion. In summary, our findings lay a solid foundation for further studies on the functions of pfcrtc2, and provide novel genetic loci for developing new strategies to control disease outbreak in teleost.

13.
Org Biomol Chem ; 22(20): 4179-4189, 2024 05 22.
Artículo en Inglés | MEDLINE | ID: mdl-38716654

RESUMEN

Aspergillus versicolor, an endophytic fungus associated with the herbal medicine Pedicularis sylvatica, produced four new polyketides, aspeversins A-D (1-2 and 5-6) and four known compounds, O-methylaverufin (2), aversin (3), varilactone A (7) and spirosorbicillinol A (8). Their structures were elucidated by extensive spectroscopic data analysis, and their absolute configurations were determined by calculated electronic circular dichroism (ECD) and Mo2(AcO)4-induced CD data. Compound 5 was found to exhibit α-glucosidase inhibitory activity with an IC50 value of 25.57 µM. An enzyme kinetic study indicated that 5 was a typical uncompetitive inhibitor toward α-glucosidase, which was supported by a molecular docking study. Moreover, compounds 1-3 and 5 also improved the cell viability of PC12 cells on a 1-methyl-4-phenylpyridinium (MPP+)-induced Parkinson's disease model, indicating their neuroprotective potential as antiparkinsonian agents.


Asunto(s)
Aspergillus , Inhibidores de Glicósido Hidrolasas , Fármacos Neuroprotectores , Policétidos , alfa-Glucosidasas , Animales , Ratas , alfa-Glucosidasas/metabolismo , Aspergillus/química , Supervivencia Celular/efectos de los fármacos , Inhibidores de Glicósido Hidrolasas/farmacología , Inhibidores de Glicósido Hidrolasas/química , Inhibidores de Glicósido Hidrolasas/aislamiento & purificación , Simulación del Acoplamiento Molecular , Estructura Molecular , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/química , Fármacos Neuroprotectores/aislamiento & purificación , Células PC12 , Policétidos/farmacología , Policétidos/química , Policétidos/aislamiento & purificación
14.
Org Biomol Chem ; 22(16): 3204-3208, 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38563260

RESUMEN

An efficient palladium-catalyzed [2 + 2 + 1] annulation of 3-iodochromones, bridged olefins, and iodomethane is described, affording a range of chromone-containing polycyclic compounds. Additionally, the corresponding deuterated products were smoothly obtained with iodomethane-d3 instead of iodomethane. Moreover, the synthetic utility of this method is further substantiated by gram scale preparation and application to late-stage modification of estrone.

15.
Artículo en Inglés | MEDLINE | ID: mdl-38981855

RESUMEN

BACKGROUND AND AIM: Insomnia has been implicated in gastrointestinal diseases (GIs), but the causal effect between insomnia and GIs and underlying mechanisms remain unknown. METHODS: By using the released summary-level data, we conducted a two-step Mendelian randomization (MR) analysis to examine the relationship between insomnia and four GIs and estimate the mediating role of candidate mediators. The first step was to investigate the causal association between insomnia and GIs using univariable MR analysis. The second step was to estimate the mediation proportion of selected mediators in these associations using multivariable MR analysis. Subsequently, results from different datasets were combined using the fixed-effect meta-analysis. RESULTS: Univariable MR analysis provided strong evidence for the causal effects of insomnia on four GIs after Bonferroni correction for multiple comparisons, including peptic ulcer disease (PUD) (odds ratio [OR] = 1.15, 95% interval confidence [CI] = 1.10-1.20, P = 1.83 × 10-9), gastroesophageal reflux (GORD) (OR = 1.19, 95% CI = 1.16-1.22, P = 5.95 × 10-42), irritable bowel syndrome (IBS) (OR = 1.18, 95% CI = 1.15-1.22, P = 8.69 × 10-25), and inflammatory bowel disease (IBD) (OR = 1.09, 95% CI = 1.03-1.05, P = 3.46 × 10-3). In the mediation analysis, body mass index (BMI) and waist-to-hip ratio (WHR) were selected as mediators in the association between insomnia and PUD (BMI: mediation proportion [95% CI]: 13.61% [7.64%-20.70%]; WHR: 8.74% [5.50%-12.44%]) and GORD (BMI: 11.82% [5.94%-18.74%]; WHR: 7.68% [4.73%-11.12%]). CONCLUSIONS: Our findings suggest that genetically instrumented insomnia has causal effects on PUD, GORD, IBS, and IBD, respectively. Adiposity traits partially mediated the associations between insomnia and GIs. Further clinical studies are warranted to evaluate the protective effect of insomnia treatment on GIs.

16.
J Phys Chem A ; 128(18): 3579-3586, 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38662918

RESUMEN

We report a high-resolution photoelectron imaging study of cryogenically cooled BiB2- and BiB3- clusters. Vibrational features are completely resolved for the ground-state detachment transitions, providing critical information about the structures of the anionic clusters and their corresponding neutrals. The electron affinities of BiB2 and BiB3 are accurately measured to be 2.174(1) and 2.121(1) eV, respectively. The B-B and Bi-B stretching frequencies are measured to be 1262 and 476 cm-1, respectively, in the ground state of BiB2. Three vibrational frequencies are measured for the ground state of BiB3: 1194 cm-1 (B-B stretching), 782 cm-1 (B-B stretching), and 339 cm-1 (Bi-B stretching). Both BiB2- and BiB3- and their neutral ground states are found to have planar C2v structures in which the Bi atom bridges two B atoms. BiB2- is found to have a triplet spin state (3B2), consistent with its complicated photoelectron spectra, whereas BiB3- is a doublet (2B1) and neutral BiB3 is closed shell (1A1). Both BiB2 and BiB3 consist of peripheral localized Bi-B and B-B σ bonds and delocalized π and σ bonds.

17.
J Nat Prod ; 87(9): 2180-2193, 2024 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-39214601

RESUMEN

Co-cultivation of isopod-associated fungi Herpotrichia sp. SF09 and Trametes versicolor SF09A led to the reciprocal induction of thirteen new compounds (1-7 and 9-13) with diverse architectures. Importantly, compounds 1 and 2 are rare fungal sesquiterpene-saccharide hybrids incorporating a xylopyranose moiety, compound (±)-3 represents the first example of a natural linear sesquiterpene racemate, and compound 7 is a rare α-pyrone derivative with a xylopyranose motif. Their structures were elucidated by analysis of NMR and mass spectrometry data, and their absolute configurations were determined by Mosher's method, microscale derivatization, and single-crystal X-ray diffraction, as well as ECD calculations. All the isolated compounds ameliorated MPP+-induced oxidative damage in PC12 cells in a dose-dependent fashion. Among them, compounds 5 and 15 showed significant protective action against neuronal injury by MPP+ at 5 µM. Meanwhile, transcriptome sequencing was performed to evaluate the molecular mechanism of the neuroprotective activity for compound 5. Results indicated that compound 5 might mitigate MPP+-induced neuronal injury through the regulation of multiple signaling pathways, including the PI3K-Akt and MAPK pathways. Our findings suggested that compound 5 could be a promising neuroprotective agent for the treatment of Parkinson's disease.


Asunto(s)
Fármacos Neuroprotectores , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/química , Animales , Células PC12 , Estructura Molecular , Ratas , Sesquiterpenos/farmacología , Sesquiterpenos/química , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/metabolismo , Polyporaceae/química , Técnicas de Cocultivo
18.
J Nat Prod ; 87(8): 1930-1940, 2024 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-39140432

RESUMEN

Eighteen nitrogen-containing compounds (1-18) were isolated from cultures of the lichen-associated Streptomyces flavidovirens collected from the Qinghai-Tibet Plateau, including seven phenazine derivatives with three new ones, named subphenazines A-C (2-4), two new furan pyrrolidones (8-9), and nine known alkaloids. The structures were elucidated by spectroscopic data analysis, and absolute configurations were determined by single-crystal X-ray diffraction and ECD calculations. The phenazine-type derivatives, in particular compound 3, exhibited significantly better antineuroinflammatory activity than other isolated compounds (8-18). Compound 3 inhibited the release of proinflammatory cytokines including IL-6, TNF-α, and PGE2, and the nuclear translocation of NF-κB; it also reduced the oxidative stress and activated the Nrf2 signaling pathway in LPS-induced BV2 microglia cells. In vivo anti-inflammatory activity in zebrafish indicated that 3 inhibited LPS-stimulated ROS generation. These findings suggested that compound 3 might be a potent antineuroinflammatory agent through the regulation of the NF-κB/Nrf2 signaling pathways.


Asunto(s)
Antiinflamatorios , Líquenes , FN-kappa B , Fenazinas , Streptomyces , Pez Cebra , Animales , Streptomyces/química , Líquenes/química , Antiinflamatorios/farmacología , Antiinflamatorios/química , Fenazinas/farmacología , Fenazinas/química , Estructura Molecular , FN-kappa B/metabolismo , Ratones , Factor 2 Relacionado con NF-E2/metabolismo , Transducción de Señal/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Microglía/efectos de los fármacos , Lipopolisacáridos/farmacología , Factor de Necrosis Tumoral alfa/metabolismo
19.
J Intensive Care Med ; 39(3): 257-267, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37723966

RESUMEN

Objectives: To investigate the effect of our improved nursing strategy on prognosis in immunosuppressed patients with pneumonia and sepsis. Methods: Immunosuppressed patients (absolute lymphocyte count <1000 cells/mm3) with pneumonia and sepsis were enrolled and divided into a control group and treatment group. The treatment group received the improved nursing strategy. The primary outcome in this study was 28-day mortality. Results: In accordance with the study criteria, 1019 patients were finally enrolled. Compared with patients in the control group, those in the treatment group had significantly fewer days on mechanical ventilation [5 (4, 7) versus 5 (4, 7) days, P = .03] and lower intensive care unit (ICU) mortality [21.1% (132 of 627) vs 28.8% (113 of 392); P = .005] and 28-day mortality [22.2% (139 of 627) vs 29.8% (117 of 392); P = .006]. The treatment group also had a shorter duration of ICU stay [9 (5, 15) vs 11 (6, 22) days, P = .0001] than the control group. The improved nursing strategy acted as an independent protective factor in 28-day mortality: odds ratio 0.645, 95% confidence interval: 0.449-0.927, P = .018. Conclusion: Our improved nursing strategy shortened the duration of mechanical ventilation and the ICU stay and decreased ICU mortality and 28-day mortality in immunosuppressed patients with pneumonia and sepsis. Trial registration: ChiCTR.org.cn, ChiCTR-ROC-17010750. Registered 28 February 2017.


Asunto(s)
Neumonía , Sepsis , Humanos , Estudios Prospectivos , Respiración Artificial , Pronóstico , Sepsis/terapia , Unidades de Cuidados Intensivos , Estudios Retrospectivos
20.
J Chem Phys ; 161(1)2024 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-38958161

RESUMEN

The evaporation-induced deposition pattern of the linear diblock copolymer solution has attracted attention in recent years. Given its critical applications, we study deposition patterns of the linear diblock copolymer solution nanodroplet on a solid surface (the wall) by molecular dynamics simulations. This study focuses on the influence of the nonbonded interaction strength, including the interaction between the wall and polymer blocks (ɛAW and ɛBW), the interaction between the solvent and the wall (ɛSW), and the interaction between polymer blocks (ɛAB). Conditions leading to diverse deposition patterns are explored, including the coffee-ring and the volcano-like structures. The formation of the coffee-ring structure is attributed to receding interfaces, the heterogeneity inside the droplet, and the self-assembly of polymer chains. This study contributes to the establishment of guidelines for designing deposition patterns of the linear diblock copolymer solution nanodroplet, which facilitates practical applications such as inkjet printing.

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