RESUMEN
This study explored the mediation of mindfulness and perceived hope between perceived social support and mental health literacy in university students. Of 568 students (205 males, 363 females, average age 20.97) from 70 Taiwanese universities, tools like the Perceived Social Support Scale, General Health Questionnaire, Mindful Attention Awareness Scale, and State Hope Scale were used, adapted to Traditional Chinese through back-translation. Confirmatory factor analysis affirmed model validity. Hayes' PROCESS Model 6 analyzed the data. The results showed an indirect effect of social support on mental health literacy via mindfulness and hope (B = 0.091, 95 % CI: 0.0613 to 0.1258). Three mediation paths were: (1) mindfulness (B = 0.035); (2) hope (B = 0.052); and (3) a combined effect (B = 0.003). A direct effect of social support on mental health literacy was significant (B = 0.120). The model explained 33.9 % of the variance in mental health literacy. The research underscores the link between social support, mindfulness, hope, and mental health literacy, identifying mindfulness and hope as mediators. It stresses the mediation impact and suggests strategies to boost mental health literacy in university students. Future research should expand to cross-cultural studies, further examine the evolving dynamics of social support, and incorporate both qualitative and experimental methodologies. The inclusion of factors such as alienation, well-being, and resilience can enrich the theoretical framework.
Asunto(s)
Alfabetización en Salud , Atención Plena , Masculino , Femenino , Humanos , Adulto Joven , Adulto , Atención Plena/métodos , Universidades , Estudiantes/psicología , Apoyo SocialRESUMEN
The fungus Nectria sp. MHHJ-3 was isolated from Illigera rhodantha. A molecular networking-guided the secondary metabolites investigation of Nectria sp. MHHJ-3 led to the isolation of ten metabolites (1-10), including two new naphthalenone derivatives, nectrianaphthalenones A (1) and B (2), and two new steroids, nectriasteroids A (3) and B (4). Their structures were elucidated by extensive spectroscopic analysis including the HRESIMS, 1D/2D NMR and electronic circular dichroism (ECD) spectra. A plausible biosynthetic pathway for 1-2 was proposed. Compounds 1 and 2 exhibited moderate acetylcholinesterase (AChE) inhibitory activities. Compounds 3 and 4 showed significant cytotoxic activity against selected tumor cells. Particularly, compound 3 exhibited the strongest activity against A549 cells with an IC50 value of 13.73 ± 0.03 µM, which was at the same grade with that of positive control cisplatin.
Asunto(s)
Antineoplásicos , Nectria , Estructura Molecular , Nectria/química , Acetilcolinesterasa , Hongos , Antineoplásicos/farmacologíaRESUMEN
Objective: This study aimed to compare the effectiveness of prehospital emergency treatments using midazolam (MDL) intramuscularly, diazepam (DZP) enema, and chloral hydrate (CH) enema in managing pediatric convulsions. Methods: A comparative observational study was conducted, and a total of 140 children with acute convulsions treated with prehospital anti-convulsions at Qinhuangdao First Hospital's emergency department between June 2015 and May 2019 were included in this study. The children were categorized based on the prehospital anti-convulsion measures received: group M (n = 48) received MDL intramuscularly, group D (n = 46) received DZP enema, and group C (n = 46) received CH enema. The emergency effects of the three treatment groups were compared. Results: 1. Group M showed significantly shorter treatment preparation time and total rescue time compared to groups C and D (both P < .05); no significant difference was observed between groups C and D (both P > .05), including convulsion control time in the effective cases (45 in group M, 42 in group C, and 43 in group D) (all P > .05 Group M had effective rates of 93.75%, while group C and group D had rates of 91.3% and 93.48%, respectively (all P > .05); Group M had more controlled cases at 1 min, 3 min, 5 min, and 10 min than group C and group D (all P > .05). Group M had significantly fewer relapses, cases requiring intravenous maintenance treatment, and faster convulsion control after intravenous maintenance compared to groups C and D (P < .05), with no significant differences between groups C and D in time to recovery of consciousness and length of hospitalization (P > .05). 4. Systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), respiratory (R) frequency, and peripheral oxygen saturation (SpO2) showed no significant differences before and 10 minutes after medication in all three groups (P > .05); SBP and DBP levels fluctuated within the normal range, while HR decreased, R frequency decreased, and SpO2 increased significantly 10 minutes after medication compared to before treatment (P < .05). 5. No significant adverse effects were observed in the three patient groups. Conclusions: MDL intramuscular injection, DZP enema, and CH enema were effective prehospital treatments for pediatric acute convulsions. MDL intramuscular injection demonstrated advantages such as fast onset, reliable efficacy, ease of use, and high safety, making it more suitable for the prehospital treatment of pediatric convulsions.
Asunto(s)
Servicios Médicos de Urgencia , Midazolam , Niño , Humanos , Hidrato de Cloral/uso terapéutico , Diazepam/uso terapéutico , Enema , Midazolam/uso terapéutico , Convulsiones/tratamiento farmacológico , Convulsiones/inducido químicamenteRESUMEN
This study aims to explore the anti-depression mechanism of Zuojin Pills based on the plasma constituents, network pharmacology, and experimental verification. UHPLC-TOF-MS was used for qualitative analysis of Zuojin Pills-containing serum. Targets of the plasma constituents and the disease were retrieved from PharmMapper and GeneCards. Then the protein-protein interaction(PPI) network was constructed and core targets were screened for GO term enrichment and KEGG pathway enrichment. Cytoscape 3.7.2 was employed construct the "compound-target-pathway" network and the targets and signaling pathways of Zuojin Pills against depression were predicted. CUMS-induced depression mouse model was established to verify the key targets. The results showed that a total of 21 constituents migrating to blood of Zuojin Pills were identified, which were mainly alkaloids. A total of 155 common targets of the constituents and the disease and 67 core targets were screened out. KEGG enrichment and PPI network analysis showed that Zuojin Pills may play a role in the treatment of depression through AMPK/SIRT1, NLRP3, insulin and other targets and pathways. Furthermore, the results of animal experiments showed that Zuojin Pills could significantly improve the depression behaviors of depression, reduce the levels of IL-1ß, IL-6 and TNF-α in hippocampus and serum, activate AMPK/SIRT1 signaling, and reduce the protein expression of NLRP3. In conclusion, Zuojin Pills may play a role in the treatment of depression by activating AMPK/SIRT1 signaling pathway, and inhibiting NLRP3 activation and neuroinflammation in the hippocampus of mice.
Asunto(s)
Medicamentos Herbarios Chinos , Farmacología en Red , Animales , Ratones , Proteínas Quinasas Activadas por AMP , Cromatografía Líquida de Alta Presión , Proteína con Dominio Pirina 3 de la Familia NLR , Sirtuina 1 , Medicamentos Herbarios Chinos/farmacología , Simulación del Acoplamiento MolecularRESUMEN
The fungus Pseudopestalotiopsis theae isolated from the fresh leaves of Illigera celebica, has been reported to be a pathogenic fungus that can cause gray blight on tea leaves, a disease characterized by the appearance of necrotic lesions on tea leaves. The pathogenic substances in this fungus have not been clearly identified. Considering the possible involvement of specialized metabolites in symptom appearance, a chemical investigation of specialized metabolites on P. theae was conducted, resulting in the isolation of eight meroterpenoids, including six undescribed biscognienynes G-L and two known ones (biscognienynes B and D). The structures of these new compounds were characterized by extensive NMR spectroscopic and HR-ESI-MS data, and their absolute configurations were elucidated by ECD calculations. Except for biscogniyne L, all the isolated biscognienynes showed different degrees of phytotoxicity to tea in vivo, thereby revealing for the first time the substances in P. theae that cause tea gray blight. Inspired by the fact that phytotoxins produced by pathogenic fungus are an effective resource for designing natural and safe bioherbicides, when assayed the herbicidal activity through Petri dish bioassays, biscognienynes G-J showed phytotoxic effects against seed germination and seedling growth of Setaria viridis, strongly inhibiting seed germination percentage and radicle and germ lengths of seedlings. The results of this study demonstrated the great potential of biscognienynes G-J to be proposed and developed as ecofriendly herbicides.
Asunto(s)
Ascomicetos , Herbicidas , Herbicidas/farmacología , Herbicidas/química , Ascomicetos/química , Plantones , TéRESUMEN
Observational studies and clinical trials have evaluated the associations between vitamin D supplementation and cancer incidence/mortality and obtained mixed results. Previous meta-analyses have also yielded inconsistent conclusions. In this paper, we conduct an updated meta-analysis by including current randomized clinical trials (RCTs) to assess the association between vitamin D supplementation and cancer incidence and mortality. The PubMed, Scopus and Embase databases were systematically searched from their inception to 6 February 2022. Fixed-effects meta-analyses were conducted. Trial sequential analyses were performed using a risk ratio reduction threshold of 10% for cancer incidence and mortality. Twenty-six RCTs were eligible, and pooled results indicated that vitamin D supplementation, compared to placebo with/without calcium, was not associated with a reduction in total cancer incidence (risk ratio: 0.98, 95% CI: 0.94, 1.02; I2 = 0%). In contrast, vitamin D supplementation significantly reduced total cancer mortality (risk ratio: 0.88, 95% CI: 0.8, 0.96; I2 = 0%). Moreover, trial sequential analysis provided reliable evidence that supplementation with vitamin D lowered the relative risk of total cancer mortality by 10%. Our updated meta-analysis suggested that vitamin D supplementation did not reduce total cancer incidence but significantly lowered total cancer mortality.Supplemental data for this article is available online at https://doi.org/10.1080/10408398.2022.2056574 .
Asunto(s)
Suplementos Dietéticos , Neoplasias , Humanos , Incidencia , Ensayos Clínicos Controlados Aleatorios como Asunto , Vitamina D/uso terapéutico , Neoplasias/tratamiento farmacológicoRESUMEN
The present study was conducted to evaluate the effects of dietary Macleaya cordata extract (MCE) supplementation on growth performance and intestinal health of American eels (Anguilla rostrata) farmed in intensive system. A total of six cement tanks of fish were randomly divided into a control group fed a commercial diet and an MCE group fed the commercial diet with 100 mg/kg MCE, respectively. There were three replicates in each group. The results suggested that 100 mg/kg MCE could improve the growth performance and intestinal health of the American eels by strengthening the barrier function and antioxidative ability in the intestine and beneficially modulating intestinal microbiota with the higher relative abundance and more species of the potential probiotics and the lower relative abundance of potentially pathogenic bacteria.
Asunto(s)
Anguilla , Probióticos , Animales , Dieta , Intestinos , Extractos Vegetales/farmacologíaRESUMEN
This study aims to explore the anti-depression mechanism of Zuojin Pills based on the plasma constituents, network pharmacology, and experimental verification. UHPLC-TOF-MS was used for qualitative analysis of Zuojin Pills-containing serum. Targets of the plasma constituents and the disease were retrieved from PharmMapper and GeneCards. Then the protein-protein interaction(PPI) network was constructed and core targets were screened for GO term enrichment and KEGG pathway enrichment. Cytoscape 3.7.2 was employed construct the "compound-target-pathway" network and the targets and signaling pathways of Zuojin Pills against depression were predicted. CUMS-induced depression mouse model was established to verify the key targets. The results showed that a total of 21 constituents migrating to blood of Zuojin Pills were identified, which were mainly alkaloids. A total of 155 common targets of the constituents and the disease and 67 core targets were screened out. KEGG enrichment and PPI network analysis showed that Zuojin Pills may play a role in the treatment of depression through AMPK/SIRT1, NLRP3, insulin and other targets and pathways. Furthermore, the results of animal experiments showed that Zuojin Pills could significantly improve the depression behaviors of depression, reduce the levels of IL-1β, IL-6 and TNF-α in hippocampus and serum, activate AMPK/SIRT1 signaling, and reduce the protein expression of NLRP3. In conclusion, Zuojin Pills may play a role in the treatment of depression by activating AMPK/SIRT1 signaling pathway, and inhibiting NLRP3 activation and neuroinflammation in the hippocampus of mice.
Asunto(s)
Animales , Ratones , Farmacología en Red , Proteínas Quinasas Activadas por AMP , Cromatografía Líquida de Alta Presión , Proteína con Dominio Pirina 3 de la Familia NLR , Sirtuina 1 , Medicamentos Herbarios Chinos/farmacología , Simulación del Acoplamiento MolecularRESUMEN
Anal pain and urinary retention are the two most outstanding complications of the procedure for prolapse and hemorrhoids (PPH) surgery. This study intended to assess the clinical effect and mechanism of Prostant on urinary retention and anal pain after the PPH. Here, 30 patients received PPH surgery. The role and mechanism of Prostant in patients and mice with urinary retention and anal pain were evaluated. ANOVA tests were executed and differences between groups were regarded as statistically significant when p < 0.05. Prostant effectively improved the urination status, lower abdomen symptoms, time to urinate and score of VAS, and the reduction of TNF-α and IL-6. Similarly, Prostant can ameliorate the outcome of urodynamics in urinary retention mice. Mechanically, Prostant reversed the urinary retention-elevated the serum level of hs-CRP and TNF-α, reduction of IL-2, imbalance of Treg/Th17, and level of JAK2 and phosphorylated STAT3. Besides, Prostant ameliorated the pain as shown by the reduction of writhing response, and the elevation of threshold of pain and degree of swelling. Moreover, Prostant antagonized the pain-induced dysregulation of Treg/Th17. Therefore, Prostant can treat patients and mice with anal pain and urinary retention by modulating the balance of Th17/Treg to regulate the secretion and production of inflammatory factors. We hope our results can establish a scientific treatment approach for solving anal pain and urinary retention after PPH surgery of mixed hemorrhoids.
RESUMEN
This study aims to explore the targets of ginsenosides in brain based on drug affinity responsive target stability(DARTS) technology. Specifically, DARTS technology was combined with label-free liquid chromatography tandem mass spectrometry(LC-MS) to screen out the proteins in the brain that might interact with ginsenosides. Based on the screening results, adenylate kinase 1(AK1) was selected for further confirmation. First, the His-AK1 fusion protein was yielded successively through the construction of recombinant prokaryotic expression vector, expression of target protein, and purification of the fusion protein. Biolayer interferometry(BLI) was employed to detect the direct interaction of Rg_1, Re, Rb_1, Rd, Rh_2, F1, Rh_1, compound K(CK), 25-OH-PPD, protopanaxa-diol(PPD), and protopanaxatriol(PPT) with AK1, thereby screening the ginsenoside monomer or sapogenin that had strong direct interaction with the suspected target protein AK1. Then, the BLI was used to further determine the kinetic parameters for the binding of PPD(strongest interaction with AK1) to His-AK1 fusion protein. Finally, molecular docking technology was applied to analyze the binding properties between the two. With DARTS and LC-MS, multiple differential proteins were screened out, and AK1 was selected based on previous research for target verification. Fusion protein His-AK1 was obtained by prokaryotic expression, and the response(nm) of Re, Rg_1, Rd, Rb_1, Rh_1, Rh_2, F1, PPT, PPD, 25-OH-PPD, and CK with His-AK1 was respectively 0.003 1, 0.001 9, 0.042 8, 0.022 2, 0.013 4, 0.037 3, 0.013 9, 0.030 7, 0.140 2, 0.016 0, and 0.040 8. The K_(on), K_(off), and K_D values of PPD and His-AK1 were determined by the BLI as 1.22×10~2 mol~(-1)·L·s~(-1), 1.04×10~(-2) s~(-1), 8.52×10~(-5) mol·L~(-1). According to the molecular docking result, PPD bound to AK1 with the absolute value of the docking score of 3.438, and hydrogen bonds mainly formed between the two. Thus, AK1 is one of the protein action sites of ginsenosides in the brain. The direct interaction between ginsenoside metabolite PPD and AK1 is the strongest.
Asunto(s)
Ginsenósidos , Encéfalo/metabolismo , Cromatografía Liquida , Simulación del Acoplamiento Molecular , TecnologíaRESUMEN
BACKGROUND: The extract of freshwater clams has been used to protect the body against liver diseases in traditional folk medicine. This study aims at investigating the effects of freshwater clam extract on activated hepatic stellate cells (aHSCs), which are critical contributors to liver fibrosis. METHODS: The aHSCs used in this study were derived from hepatic stellate cells that were isolated and purified from the livers of male Wistar rats and then transformed into the activated phenotype by culturing on uncoated plastic dishes. Freshwater clam extract (CE) was collected after the outflow from the live freshwater clams in a water bath at 100°C for 60 min. The effects of CE on aHSCs were analyzed by MTT assay, flow cytometry, Oil Red O (ORO) staining, western blot, and real-time RT-PCR. RESULTS: The results indicated that CE suppressed the proliferation of aHSCs through G0/G1 cell cycle arrest by downregulating cyclin D1 and upregulating p27. The expression levels of a-SMA, collagen I, TGF-ß, and TNF-α were inhibited in the CE-treated aHSCs. In addition, the CE treatment increased the lipid contents in aHSCs by promoting PPARγ expression. Furthermore, CE modulated the expression of ECM-related genes, i.e., by upregulating MMP-9 and downregulating TIMP-II. CONCLUSIONS: These data revealed that CE could induce the deactivation of aHSCs. We therefore suggest that CE has potential as an adjuvant therapeutic agent against hepatic fibrosis.
RESUMEN
Adjuvant concurrent chemoradiotherapy (CCRT) is the standard care for patients with resected advanced gastric cancer, but its survival benefits remain undetermined in patients undergoing D2 lymph node dissection (D2 dissection). We evaluated safety and efficacy of adjuvant CCRT with 5-fluorouracil (5-FU) versus chemotherapy alone in 110 gastric cancer patients with D2 dissection treated in Taiwan between January 2009 and January 2013. All the 71 patients receiving adjuvant CCRT were treated with daily infusional 5-FU and radiotherapy. Adjuvant CCRT was associated with higher risks of major hematologic (56.3% vs. 23.8%, p = 0.002) and gastrointestinal (46.9% vs. 14.3%, p = 0.027) toxicities and death (12.5% vs. 0.0%, p = 0.041) in patients above 70 years old, but this was not the case in those ≤70 years of age. Univariate Cox proportional regressions identified adjuvant CCRT as a factor for better overall survival (OS) (hazard ratio [HR]=0.52; 95% confidence interval [CI]: 0.27-0.99) and disease-free survival (DFS) (HR=0.46, 95% CI: 0.24-0.88), but it was not a significant factor for OS or DFS after adjusting for other factors in the multivariate analysis. However, in stratified analyses by age, we found adjuvant CCRT was an independent prognostic factor for better OS (HR=0.07; 95% CI: 0.01-0.38) in patients ≤70 years old, but not in those above 70 years of age. Therefore, it was concluded that age may to be a modifier of the effects of adjuvant CCRT.
Asunto(s)
Envejecimiento , Antimetabolitos Antineoplásicos/administración & dosificación , Antimetabolitos Antineoplásicos/uso terapéutico , Quimioradioterapia Adyuvante/métodos , Fluorouracilo/administración & dosificación , Fluorouracilo/uso terapéutico , Neoplasias Gástricas/terapia , Adulto , Anciano , Anciano de 80 o más Años , Antimetabolitos Antineoplásicos/efectos adversos , Quimioradioterapia Adyuvante/efectos adversos , Supervivencia sin Enfermedad , Femenino , Fluorouracilo/efectos adversos , Humanos , Infusiones Intravenosas , Escisión del Ganglio Linfático/métodos , Masculino , Persona de Mediana Edad , Pronóstico , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/cirugía , Análisis de Supervivencia , Taiwán , Resultado del TratamientoRESUMEN
Esculetin, a natural derivative from the traditional and widely-used Chinese medicinal herb Cortex Fraxini, has a variety of pharmacological effects, especially in anti-inflammation. However, it is not clear whether esculetin has a therapeutic effect on sepsis. This study aimed to investigate the anti-inflammatory and protective effects of esculetin on early sepsis. The results showed that the lung injury was significantly relieved with the treatment of esculetin, accompanied with the restrained production of inflammatory factors including IL-1ß, IL-6, TNF-α, CCL2 and iNOS during the early phase of E.coli-induced sepsis. Of note, activation of NF-κB and STAT1/STAT3 signals, the main upstream signals of many inflammatory factors, were attenuated by esculetin in both lung tissues from septic mice and LPS-stimulated macrophage. These findings suggested that the protection of esculetin against early sepsis should be related to its anti-inflammatory effect, which was at least partly due to its inhibition on NF-κB and STAT1/STAT3 signaling pathway in macrophage. Thus, esculetin could serve as a potential therapeutic agent by rebalancing innate immune response in macrophage for the treatment of early sepsis.
Asunto(s)
FN-kappa B , Sepsis , Transducción de Señal/efectos de los fármacos , Umbeliferonas/farmacología , Animales , Inflamación/tratamiento farmacológico , Lipopolisacáridos , Ratones , FN-kappa B/antagonistas & inhibidores , Factor de Transcripción STAT1/antagonistas & inhibidores , Factor de Transcripción STAT3/antagonistas & inhibidores , Sepsis/tratamiento farmacológicoRESUMEN
Aralia elata (Miq.) Seem is widely used as a medicinal plant and functional food in China. In this study, A. elata plants were exposed to full sunlight (CK), 40% shading (LS), 60% shading (MS), and >80% shading (ES) condition to investigate the effects of shading treatments on growth, stress levels, antioxidant enzymes activity, araloside content and related gene expression. The greatest growth and leaf biomass were achieved in 40% shading, and leaf biomass per plant increased by 16.09% compared to the non-shading treatment. Furthermore, the lowest reactive oxide species (ROS) production and lipid peroxidation resulting from increasing antioxidant enzyme activity were also observed in LS treatment. Overall, shading percentage negatively regulated the expression of key enzymes (squalene synthase, SS; squalene epoxidase, SE and ß-amyrin synthase, bAS) involved in the saponin biosynthesis, resulting in the greatest yields of total and four selected aralosides in A. elata leaves were achieved in sunlight group. However, the greatest yield of total saponin in the leaves was observed in the 40% shading group due to higher leaf biomass. The results suggest that optimizing the field growing conditions would be important for obtaining the greatest yield of bioactive components. Total saponin and selected aralosides also have a significant correlation with ROS production and antioxidant enzyme activity, these indicated the increased yield of these saponins may be part of a defense response. The study concludes that the production of saponin was the interaction of oxidative stress and photosynthesis.
Asunto(s)
Aralia , Oscuridad , Hojas de la Planta/efectos de la radiación , Saponinas/metabolismo , Triterpenos/metabolismo , Aralia/genética , Aralia/efectos de la radiación , Regulación de la Expresión Génica de las PlantasRESUMEN
The present study investigated the effects and mechanisms of Jiaotai Pills on depressed mice induced by chronic unpredictable mild stress(CUMS). The CUMS-induced depression model mice were established and the depression behaviors of mice were evaluated by sucrose preference test, open field test, tail suspension test, and forced swimming test. Molecular docking was employed to simulate the interaction of six main active ingredients in Jiaotai Pills with SIRT1. Immunohistochemical staining was used to detect the level of SIRT1 in the hippocampus of mice. Western blot was used to detect the protein expression levels of SIRT1, p-NF-κB p65, NF-κB p65, and FoxO1 in the hippocampus of mice. Enzyme-linked immunosorbent assay(ELISA) kits were used to detect the levels of interleukin(IL)-1ß, IL-6, tumor necrosis factor-α(TNF-α), and brain-derived neurotrophic factor(BDNF) in the hippocampus and serum of mice. Biochemical kits were used to detect superoxide dismutase(SOD) activity and malondialdehyde(MDA) and glutathione(GSH) levels in the hippocampus and serum of mice. Liquid chromatography-tandem mass spectrometry(LC-MS/MS) was used to detect the levels of dopamine(DA), 5-hydroxytryptamine(5-HT), and norepinephrine(NE) in the hippocampus and serum of mice. The results showed that the sucrose preference rate, movement distance, and the number of crossing centers were reduced in the model group(P<0.01), and the tail suspension time and swimming immobility time were increased(P<0.01). Molecular docking results indicated good binding of six main active ingredients in Jiaotai Pills to SIRT1. In the hippocampus, the expression level of SIRT1 was reduced(P<0.01), and the levels of p-NF-κB p65/NF-κB p65 and FoxO1 were increased(P<0.01). In the hippocampus and serum, the levels of IL-1ß, IL-6, TNF-α, and MDA were increased(P<0.01), and the activity of SOD and the levels of GSH, DA, 5-HT, NE, and BDNF were reduced(P<0.01). The treatment with high-dose Jiaotai Pills increased the sucrose preference rate, movement distance, and the number of crossing centers(P<0.05), reduced tail suspension time and swimming immobility time(P<0.01), elevated hippocampal SIRT1 expression level(P<0.01), decreased hippocampal and serum IL-1ß, IL-6, TNF-α, and MDA levels(P<0.01), potentiated SOD activity, and up-regulated GSH, DA, 5-HT, NE, and BDNF levels in the hippocampus and serum(P<0.05, P<0.01) in model mice. In conclusion, the results showed that Jiaotai Pills could improve the depression behaviors of model mice with CUMS-induced depression, and the underlying mechanism was related to the up-regulation of SIRT1 in the hippocampus of mice to exert anti-inflammatory and anti-oxidative stress effects.
Asunto(s)
Antidepresivos , Depresión , Animales , Conducta Animal , Cromatografía Liquida , Depresión/tratamiento farmacológico , Depresión/etiología , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos , Hipocampo , Ratones , Simulación del Acoplamiento Molecular , Sirtuina 1/genética , Estrés Psicológico , Espectrometría de Masas en TándemRESUMEN
Objective:To study the material basis and potential molecular mechanism of Epimedii Folium against osteoporosis. Method:The chemical components in 14 batches of Epimedii Folium were analyzed by ultra-performance liquid chromatography-quadrupole-time of flight-tandem mass spectrometry (UPLC-Q-TOF-MS/MS). With the activity of alkaline phosphatase (ALP) as the pharmacodynamic index,the partial least squares regression analysis (PLSR) was conducted to establish a model uncovering the spectrum-effect relationship between UPLC-Q-TOF-MS/MS spectral peak and ALP activity and screen the active components against osteoporosis. Online databases such as the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP),Comparative Toxicogenomics Database (CTD),Database for Annotation,Visualization,and Integrated Discovery (DAVID) and Cytoscape 3.6.1 were employed to predict the possible mechanism of action of Epimedii Folium against osteoporosis. Result:A total of 61 peaks and 56 compounds were identified by UPLC-Q-TOF-MS/MS. PLSR showed that icariin,baohuoside Ⅰ,epimedin A,sagittatoside A,and baohuoside Ⅱ might be the active components for Epimedii Folium to inhibit osteoporosis considering their strong correlation with ALP activity. As revealed by the network pharmacological analysis of the five components mentioned above,Epimedii Folium<italic> </italic>mainly regulated seven targets such as tumor necrosis factor (TNF),androgen receptor (AR),and estrogen receptor 1 (ESR1) and eight key pathways like endocrine and other factor-regulated calcium reabsorption,vascular endothelial growth factor (VEGF) signaling pathway,and transient receptor potential (TRP) channels to exert its anti-osteoporosis effect. Conclusion:The exploration of material basis and potential molecular mechanism of Epimedii Folium against osteoporosis based on UPLC-Q-TOF-MS/MS,spectrum-effect relationship,and network pharmacology has provided an experimental basis for the scientific explanation and clinical application of Epimedii Folium in treating osteoporosis.
RESUMEN
The present study investigated the effects and mechanisms of Jiaotai Pills on depressed mice induced by chronic unpredictable mild stress(CUMS). The CUMS-induced depression model mice were established and the depression behaviors of mice were evaluated by sucrose preference test, open field test, tail suspension test, and forced swimming test. Molecular docking was employed to simulate the interaction of six main active ingredients in Jiaotai Pills with SIRT1. Immunohistochemical staining was used to detect the level of SIRT1 in the hippocampus of mice. Western blot was used to detect the protein expression levels of SIRT1, p-NF-κB p65, NF-κB p65, and FoxO1 in the hippocampus of mice. Enzyme-linked immunosorbent assay(ELISA) kits were used to detect the levels of interleukin(IL)-1β, IL-6, tumor necrosis factor-α(TNF-α), and brain-derived neurotrophic factor(BDNF) in the hippocampus and serum of mice. Biochemical kits were used to detect superoxide dismutase(SOD) activity and malondialdehyde(MDA) and glutathione(GSH) levels in the hippocampus and serum of mice. Liquid chromatography-tandem mass spectrometry(LC-MS/MS) was used to detect the levels of dopamine(DA), 5-hydroxytryptamine(5-HT), and norepinephrine(NE) in the hippocampus and serum of mice. The results showed that the sucrose preference rate, movement distance, and the number of crossing centers were reduced in the model group(P<0.01), and the tail suspension time and swimming immobility time were increased(P<0.01). Molecular docking results indicated good binding of six main active ingredients in Jiaotai Pills to SIRT1. In the hippocampus, the expression level of SIRT1 was reduced(P<0.01), and the levels of p-NF-κB p65/NF-κB p65 and FoxO1 were increased(P<0.01). In the hippocampus and serum, the levels of IL-1β, IL-6, TNF-α, and MDA were increased(P<0.01), and the activity of SOD and the levels of GSH, DA, 5-HT, NE, and BDNF were reduced(P<0.01). The treatment with high-dose Jiaotai Pills increased the sucrose preference rate, movement distance, and the number of crossing centers(P<0.05), reduced tail suspension time and swimming immobility time(P<0.01), elevated hippocampal SIRT1 expression level(P<0.01), decreased hippocampal and serum IL-1β, IL-6, TNF-α, and MDA levels(P<0.01), potentiated SOD activity, and up-regulated GSH, DA, 5-HT, NE, and BDNF levels in the hippocampus and serum(P<0.05, P<0.01) in model mice. In conclusion, the results showed that Jiaotai Pills could improve the depression behaviors of model mice with CUMS-induced depression, and the underlying mechanism was related to the up-regulation of SIRT1 in the hippocampus of mice to exert anti-inflammatory and anti-oxidative stress effects.
Asunto(s)
Animales , Ratones , Antidepresivos , Conducta Animal , Cromatografía Liquida , Depresión/etiología , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos , Hipocampo , Simulación del Acoplamiento Molecular , Sirtuina 1/genética , Estrés Psicológico , Espectrometría de Masas en TándemRESUMEN
The rat everted intestinal sac model was adopted to investigate the absorption of total flavonoids from Coreopsis tinctoria in different intestinal segments. Cyaniding-3-O-β-D-glucoside, chlorogenic acid, flavanomarein, quercetagetin-7-O-β-D-glucoside, iso-okanin, marein and 3,5-dicaffeoylquinic acid which as the major chemical components of total flavonoids from C. tinctoria were selec-ted as the study objects to evaluate the absorption characteristics of each component in different intestinal segments. The results showed that the absorption of seven components of total flavonoids at different intestinal segments was in consistent with zero order absorption rate. The K_a of chlorogenic acid, flavanomarein, quercetagetin-7-O-β-D-glucoside, isookanin and 3,5-dicaffeoylquinic acid increased with increasing of concentration of total flavonoids(P<0.05), indicating that the intestinal absorption of these five components was passive transport. The K_a of cyaniding-3-O-β-D-glucoside and marein showed a weak concentration dependence, suggesting that the absorption of them may be an positive and passive co-existing mode. The result of absorption in different intestinal segments showed that cyaniding-3-O-β-D-glucoside, chlorogenic acid, flavanomarein, quercetagetin-7-O-β-D-glucoside, marein and 3,5-dicaffeoylquinic acid were mainly absorbed in ileum, while isookanin was mainly absorbed in jejunum. The total flavonoids of C. tinctoria are selectively absorbed in intestinal tract, the rat everted intestinal sac model can be used to evaluate the multi-component intestinal absorption characteristics of total flavonoids from C. tinctoria.
Asunto(s)
Animales , Ratas , Ácido Clorogénico , Coreopsis , Flavonoides , Absorción Intestinal , Extractos VegetalesRESUMEN
BACKGROUND: FAmily CEntered (FACE) Advance Care Planning helps family decision makers to understand and honor patients' preferences for future health care, if patients cannot communicate. Spiritual well-being is a key domain of pediatric oncology care and an integral dimension of pediatric advance care planning. PROCEDURE: As part of four-site randomized controlled trial of FACE for teens with cancer, the functional assessment of chronic illness therapy-spiritual well-being- version 4 (FACIT-Sp-EX-4) was completed independently by 126 adolescents with cancer/family dyads. The prevalence-adjusted and bias-adjusted kappa (PABAK) measured congruence on FACIT-Sp-EX-4. RESULTS: Adolescents (126) had mean age of 16.9 years, were 57% female and 79% White. Religious/spiritual classifications were: Catholic (n = 18), Protestant (n = 76), Mormon (n = 3), none/atheist (n = 22), other (n = 5), and unknown (n = 2). Agreement at item level between spiritual well-being of adolescents and families was assessed. Three items had ≥90% agreement and Excellent PABAK: "I have a reason for living," "I feel loved," "I feel compassion for others in the difficulties they are facing." Three items had <61% agreement and Poor PABAK: "I feel a sense of harmony within myself," "My illness has strengthened my faith or spiritual beliefs," "I feel connected to a higher power (or God)." Dyadic congruence was compared by social-demographics using median one-way analysis. Male family members (median = 72%) were less likely to share spiritual beliefs with their adolescent than female family members (median = 83%), P = .0194. CONCLUSIONS: Family members may not share spiritual beliefs with adolescents and may be unaware of the importance of spiritual well-being for adolescents.
Asunto(s)
Conducta del Adolescente , Planificación Anticipada de Atención/estadística & datos numéricos , Toma de Decisiones , Familia/psicología , Neoplasias/psicología , Religión y Medicina , Espiritualidad , Adolescente , Adulto , Estudios Transversales , Femenino , Estudios de Seguimiento , Humanos , Estudios Longitudinales , Masculino , Neoplasias/terapia , Pronóstico , Método Simple Ciego , Adulto JovenRESUMEN
Importance: The associations of spiritual and religious factors with patient-reported outcomes among adolescents with cancer are unknown. Objective: To model the association of spiritual and religious constructs with patient-reported outcomes of anxiety, depressive symptoms, fatigue, and pain interference. Design, Setting, and Participants: This cross-sectional study used baseline data, collected from 2016 to 2019, from an ongoing 5-year randomized clinical trial being conducted at 4 tertiary-referral pediatric medical centers in the US. A total of 366 adolescents were eligible for the clinical trial, and 126 were randomized; participants had to be aged 14 to 21 years at enrollment and be diagnosed with any form of cancer. Exclusion criteria included developmental delay, scoring greater than 26 on the Beck Depression Inventory II, non-English speaking, or unaware of cancer diagnosis. Exposures: Spiritual experiences, values, and beliefs; religious practices; and overall self-ranking of spirituality's importance. Main Outcomes and Measures: Variables were taken from the Brief Multidimensional Measurement of Religiousness/Spirituality (ie, feeling God's presence, daily prayer, religious service attendance, being very religious, and being very spiritual) and the spiritual well-being subscales of the Functional Assessment of Chronic Illness Therapy (meaning/peace and faith). Predefined outcome variables were anxiety, depressive symptoms, fatigue, and pain interference from Patient-Reported Outcomes Measurement Information System pediatric measures. Results: A total of 126 individuals participated (72 [57.1%] female participants; 100 [79.4%] white participants; mean [SD] age, 16.9 [1.9] years). Structural equation modeling showed that meaning and peace were inversely associated with anxiety (ß = -7.94; 95% CI, -12.88 to -4.12), depressive symptoms (ß = -10.49; 95% CI, -15.92 to -6.50), and fatigue (ß = -8.90; 95% CI, -15.34 to -3.61). Feeling God's presence daily was indirectly associated with anxiety (ß = -3.37; 95% CI, -6.82 to -0.95), depressive symptoms (ß = -4.50; 95% CI, -8.51 to -1.40), and fatigue (ß = -3.73; 95% CI, -8.03 to -0.90) through meaning and peace. Considering oneself very religious was indirectly associated with anxiety (ß = -2.81; 95% CI, -6.06 to -0.45), depressive symptoms (ß = -3.787; 95% CI, -7.68 to -0.61), and fatigue (ß = -3.11, 95% CI, -7.31 to -0.40) through meaning and peace. Considering oneself very spiritual was indirectly associated with anxiety (ß = 2.11; 95% CI, 0.05 to 4.95) and depression (ß = 2.8, 95% CI, 0.07 to 6.29) through meaning and peace. No associations were found between spiritual scales and pain interference. Conclusions and Relevance: In this study, multiple facets of spirituality and religiousness were associated with anxiety, depression, and fatigue, all of which were indirectly associated with the participant's sense of meaning and peace, which is a modifiable process. Although these results do not establish a causal direction, they do suggest palliative interventions addressing meaning-making, possibly including a spiritual or religious dimension, as a novel focus for intervention development.