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1.
J Ethnopharmacol ; 330: 118223, 2024 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-38642624

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Leonurus japonicus Houtt. (Labiatae), commonly known as Chinese motherwort, is a herbaceous flowering plant that is native to Asia. It is widely acknowledged in traditional medicine for its diuretic, hypoglycemic, antiepileptic properties and neuroprotection. Currently, Leonurus japonicus (Leo) is included in the Pharmacopoeia of the People's Republic of China. Traditional Chinese Medicine (TCM) recognizes Leo for its myriad pharmacological attributes, but its efficacy against ICH-induced neuronal apoptosis is unclear. AIMS OF THE STUDY: This study aimed to identify the potential targets and regulatory mechanisms of Leo in alleviating neuronal apoptosis after ICH. MATERIALS AND METHODS: The study employed network pharmacology, UPLC-Q-TOF-MS technique, molecular docking, pharmacodynamic studies, western blotting, and immunofluorescence techniques to explore its potential mechanisms. RESULTS: Leo was found to assist hematoma absorption, thus improving the neurological outlook in an ICH mouse model. Importantly, molecular docking highlighted JAK as Leo's potential therapeutic target in ICH scenarios. Further experimental evidence demonstrated that Leo adjusts JAK1 and STAT1 phosphorylation, curbing Bax while augmenting Bcl-2 expression. CONCLUSION: Leo showcases potential in mitigating neuronal apoptosis post-ICH, predominantly via the JAK/STAT mechanism.


Assuntos
Apoptose , Hemorragia Cerebral , Leonurus , Simulação de Acoplamento Molecular , Farmacologia em Rede , Neurônios , Animais , Apoptose/efeitos dos fármacos , Leonurus/química , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Camundongos , Masculino , Hemorragia Cerebral/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/isolamento & purificação , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Janus Quinase 1/metabolismo , Fator de Transcrição STAT1/metabolismo , Modelos Animais de Doenças
2.
Dev Psychopathol ; : 1-11, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38179683

RESUMO

Childhood maltreatment is an established risk factor for psychopathology. However, it remains unclear how childhood traumatic events relate to mental health problems and how the brain is involved. This study examined the serial mediation effect of brain morphological alterations and emotion-/reward-related functions on linking the relationship from maltreatment to depression. We recruited 156 healthy adolescents and young adults and an additional sample of 31 adolescents with major depressive disorder for assessment of childhood maltreatment, depressive symptoms, cognitive reappraisal and anticipatory/consummatory pleasure. Structural MRI data were acquired to identify maltreatment-related cortical and subcortical morphological differences. The mediation models suggested that emotional maltreatment of abuse and neglect, was respectively associated with increased gray matter volume in the ventral striatum and greater thickness in the middle cingulate cortex. These structural alterations were further related to reduced anticipatory pleasure and disrupted cognitive reappraisal, which contributed to more severe depressive symptoms among healthy individuals. The above mediating effects were not replicated in our clinical group partly due to the small sample size. Preventative interventions can target emotional and reward systems to foster resilience and reduce the likelihood of future psychiatric disorders among individuals with a history of maltreatment.

3.
Horm Metab Res ; 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-37956980

RESUMO

The aim of this study is to report the risk factors of severe statin induced liver injury (SILI). From the database of Shandong ADR Monitoring Center and Outpatients and inpatients in our hospital, SILI cases reported from 2013 to 2021 were extracted and screened. The diagnostic criteria of SILI, the inclusion and exclusion criteria of severe and general SILI were established separately. After the SILI cases were selected and confirmed, the socio-demographic and clinical characteristics were collected. Single factor chi-square test and multi-factor unconditional logistic regression analysis were used to analyze the influencing factors of severe SILI. From 1391 reported cases, 1211 met SILI diagnostic criteria, of which 157 were severe SILI and 964 were general SILI. Univariate analysis showed that age, drug combination, statin category were the influencing factors of severe SILI (p<0.1). Multivariate logistic analysis showed that drug combination and statin category were the influencing factors of severe SILI (p<0.05). Atorvastatin caused the most serious SILI, and its risk is 1.77 times higher than rosuvastatin. The serious SILI risk of drug combination was 2.08 times higher than statin alone. The patient with these factors should be monitored intensively during clinical treatment, to ensure their medication safety.

4.
Oncol Lett ; 25(6): 257, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37485421

RESUMO

Since primary retroperitoneal liposarcoma (PRPLS) is rare in the clinic, related clinical studies are lacking. The present study was designed to investigate the predictive factors of short-term (≤1 year) recurrence (STR) and construct a novel nomogram of local recurrence-free survival (LRFS) for surgically resected PRPLS. A total of 128 PRPLS cases who underwent radical surgery were retrospectively analyzed. Based on the interval from the operation to tumor recurrence, the predictors of STR were screened using univariate and multivariate logistic regression analyses. Cox proportional hazard regression models were applied to identify the predictors of LRFS. Furthermore, the independent predictors acquired from multivariate analyses were used to construct a nomogram. Multivariate logistic regression analysis revealed that age ≥55 years [odds ratio (OR)=5.607, P=0.010], operative time ≥260 min (OR=9.716, P=0.005) and tumor necrosis (OR=3.781, P=0.037) were independent risk factors of STR for PRPLS. In the Cox regression analysis, clinical symptoms [hazard ratio (HR)=1.746, P=0.017], resection method (OR=0.370, P=0.021) and de-differentiated histological subtype (HR=1.975, P=0.048) were identified as independent predictors of LRFS. Subsequently, the independent predictors acquired from multivariate analyses were used to construct a nomogram for LRFS. Age, operative time, tumor necrosis, clinical symptoms, resection method and histological subtype were related to recurrence for surgically resected PRPLS and a novel nomogram was constructed based on the above predictors.

5.
Phys Chem Chem Phys ; 25(12): 8515-8523, 2023 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-36883530

RESUMO

All-solid-state lithium-sulfur batteries (ASSLSBs) have high reversible characteristics owing to the high redox potential, high theoretical capacity, high electronic conductivity, and low Li+ diffusion energy barrier in the cathode. Monte Carlo simulations with cluster expansion, based on the first-principles high-throughput calculations, predicted a phase structure change from Li2FeS2 (P3̄M1) to FeS2 (PA3̄) during the charging process. LiFeS2 is the most stable phase structure. The structure of Li2FeS2 after charging was FeS2 (P3̄M1). By applying the first-principles calculations, we explored the electrochemical properties of Li2FeS2 after charging. The redox reaction potential of Li2FeS2 was 1.64 to 2.90 V, implying a high output voltage of ASSLSBs. Flatter voltage step plateaus are important for improving the electrochemical performance of the cathode. The charge voltage plateau was the highest from Li0.25FeS2 to FeS2 and followed from Li0.375FeS2 to Li0.25FeS2. The electrical properties of LixFeS2 remained metallic during the Li2FeS2 charging process. The intrinsic Li Frenkel defect of Li2FeS2 was more conducive to Li+ diffusion than that of the Li2S Schottky defect and had the largest Li+ diffusion coefficient. The good electronic conductivity and Li+ diffusion coefficient of the cathode implied a better charging/discharging rate performance of ASSLSBs. This work theoretically verified the FeS2 structure after Li2FeS2 charging and explored the electrochemical properties of Li2FeS2.

6.
J Econ Entomol ; 116(1): 181-191, 2023 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-36412250

RESUMO

In China, Hyphantria cunea (Drury) is an invasive phytophagous pest; it attacks nearly all species of defoliated trees. To develop integrated pest management programs (IPM) for H. cunea, we need to ensure the availability of insects by mass-rearing them on artificial diets under laboratory conditions. This study compared the growth characteristics, nutritional indices, growth indices, and digestive enzyme activity of insects reared on Pterocarya stenoptera C.DC (Fagales: Juglandaceae), the Chinese wingnut, and an artificial diet. We also investigated the correlation between diet components and growth indices using principal components analysis and Pearson correlation analysis. We found that mass-rearing of H. cunea on an artificial diet was feasible. It led to a shorter developmental period, with heavier larvae and pupae than natural diets. The principal components analysis indicated that the growth indices and α-Amylase were significantly positively associated with PC1, which explained 82.45% of the total data variability. Pearson correlation analysis showed a significant correlation between digestion, absorption parameters, and growth. Developing a mass-rearing program to produce H. cunea on an artificial diet will be valuable for improving IPM strategies. Understanding the mechanism of the responses of phytophagous insect populations to anthropogenic diet regulation can provide new ideas and methods for pest control.


Assuntos
Mariposas , Animais , Estudos de Viabilidade , Larva , Dieta , China
7.
Brain Behav ; 13(1): e2843, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36527242

RESUMO

METHODS: The databases Pubmed, and the National Library of Medicine were searched for literature. All papers on celebral stroke and transient receptor potential ion channels were considered. RESULTS: Stroke is the second leading cause of death and disability, with an increasing incidence in developing countries. About 75 per cent of strokes are caused by occlusion of cerebral arteries, and substantial advances have been made in elucidating mechanisms how stroke affects the brain. Transient receptor potential (TRP) ion channels are calcium-permeable channels highly expressed in brain that drives Ca2+ entry into multiple cellular compartments. TRPC1/3/4/6, TRPV1/2/4, and TRPM2/4/7 channels have been implicated in stroke pathophysiology. CONCLUSIONS: Although the precise mechanism of transient receptor potential ion channels in cerebral stroke is still unclear, it has the potential to be a therapeutic target for patients with stroke if developed appropriately. Hence, more research is needed to prove its efficacy in this context.


Assuntos
Acidente Vascular Cerebral , Canais de Cátion TRPM , Canais de Potencial de Receptor Transitório , Humanos , Encéfalo/metabolismo , Cálcio/metabolismo , Canais de Cátion TRPM/metabolismo
8.
Soc Sci Med ; 315: 115538, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36402011

RESUMO

The labor migration in China often leads to parent-child separation. Research to date has primarily focused on understanding mental and cognitive outcomes for children exposed to parent-child separation, with little consideration for the cumulative effects of intergenerational continuity of parent-child separation. A total of 2729 children between the ages of 4 and 6, along with one parent (primarily mothers, 86.2%) and/or one primary caregiver (if the child is separated from both parents), were recruited in the rural area of Anhui Province, China. A unique subsample of children (n = 249) with persistent experience of parent-child separation or whose mother reported being left behind by her parents during early childhood were enrolled for cognitive assessment. A total of 239 age-, gender- and residence-matched children without any parent-child separation experience were selected as the control group. Child cognitive performance was examined with the Chinese version of the Wechsler Preschool and Primary Scale of Intelligence, Fourth edition (WPPSI-IV). The association between intergenerational continuity of parent-child separation and child cognition was described using multivariate OLS regression models. Compared to mother-offspring dyads without any history of parent-child separation, girls (n = 236/450, 52.4%) who experienced the intergenerational continuity of parent-child separation showed a significant decrease of 5.73 points (95% CI: -9.83, -1.62; p = 0.006) on full-scale intelligence quotient (FSIQ) and a decrease of 5.71 points (95% CI: -9.80, 1.63; p = 0.006) on verbal comprehension index. No similar result was observed in boys. The cumulative effects of parent-child separation among mother-offspring dyads on child cognitive development highlight the need for effective early intervention to break the intergenerational cycle of disadvantage. Sex differences and possible epigenetic mechanisms underlying the intergenerational effects of parent-child separation warrant further investigation.


Assuntos
Desenvolvimento Infantil , Mães , Pré-Escolar , Feminino , Humanos , Masculino , Criança , China , Cognição , Relações Pais-Filho
9.
Phytochemistry ; 204: 113449, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36170888

RESUMO

Six undescribed triterpenoids (euphokanols A-F), two undescribed C21-steroidal glycosides (euphokanosides A and B), together with fifty-four known compounds were isolated from the roots of Euphorbia kansui. Their structures were demonstrated by extensive spectroscopic data (1D, 2D NMR and HR-ESI-MS), and the absolute configuration of euphokanol A was elucidated based on electronic circular dichroism (ECD) calculation. Among them, euphokanol A was a tetracyclic triterpenoid with a 5,10-epoxy moiety and concurrent rearrangement of Me-19(10 â†’ 9) and Me-30 (14 â†’ 8), while euphokanols B and C were rare 19(10 â†’ 9) abeo-tirucallane-type triterpenoids with Δ5(10) double bonds and 7,8-epoxy moieties. In addition, ten C21-steroidal glycosides were isolated from Euphorbia plants for the first time. Moreover, cynotophylloside B, caudatin, 5α,8α-epidioxy-22E-ergosta-6,22-diene-3ß-ol, 6ß,7ß-epoxy-3ß,4ß,5ß-trihydroxyl-20-deoxyingenol, 13-hydroxyingenol-3-(2,3- dimethylbutanoate)-13-dodecanoate, ingenol, 3-O-benzoyl-13-O-dodecanoateingenol, 3-O-(2'E,4'Z-decadienoyl)-20-O-acetylingenol, 20-O-acetylingenol and 20- deoxyingenol exhibited significant inhibition on NO production with IC50 values of 9.10, 17.38, 1.71, 0.55, 0.57, 12.22, 0.56, 0.30, 11.21 and 2.98 µM, respectively. Furthermore, wilfoside KIN, cynsaccatol L, kanesulone A, and 3ß,7ß,15ß-triacetyloxy-5α-benzoyloxy-2α,8α-dihydroxyjatropha-6(17),11E-diene-9, 14-dione showed cytotoxicity against HepG2 cell line, with IC50 values of 12.55, 12.61, 18.24 and 18.26 µM, respectively. 13-Hydroxyingenol-3-(2,3-dimethylbutanoate)-13- dodecanoate exhibited anti-proliferation activity on MCF-7 cell line with an IC50 value of 17.12 µM. Specifically, euphol selectively inhibited the growth of human glioma stem cells (GSC-3# and GSC-12#), with IC50 values of 8.89 and 13.00 µM, respectively.

10.
IEEE Trans Cybern ; PP2022 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-36170392

RESUMO

In this article, two novel adaptive fault-tolerant control schemes for a class of nonlinear strict-feedback cyber-physical systems (CPSs) with deception attacks are presented. Deception attacks, such as false data-injection attacks, which destroy sensor networks, make the outputs and states of the CPSs unavailable. It is very difficult and challenging for a designer to achieve the tracking control under the circumstance of cyberattacks. To realize the tracking control for the studied CPSs, we propose a new coordinate transformation technology without precedent, where it takes the attack gains into account and uses the compromised states to design the corresponding controllers. In the backstepping design process, Nussbaum functions are presented to alleviate the influence of the unknown attack gains. Furthermore, we consider the actuator faults problem, which includes the loss of effectiveness and the bias fault. By skillfully designing the adaptive laws, the effect of actuator faults is completely eliminated. It is theoretically proved that the first proposed tracking control scheme can guarantee all signals in the closed-loop system are bounded and the output can track the desired reference signal. In addition, the second adaptive control scheme is also developed for the CPSs under the actuator faults and a more general assumption on the deception attacks is proposed simultaneously. Finally, the feasibility of the new proposed methods is verified by MATLAB simulation analysis.

11.
Eur J Clin Pharmacol ; 78(11): 1739-1747, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36087142

RESUMO

BACKGROUND: Gamma-aminobutyric acid (GABA) analogs are being used by an increasing number of reproductive-age women. However, there is concern regarding the teratogenic potential of GABA analogs. METHODS: We performed this systematic review and meta-analysis to assess the relationship between GABA analog exposure and risk of adverse neonatal outcomes. RESULTS: Eight cohort studies were included in the meta-analysis. Exposure to a GABA analog during pregnancy was not associated with an increased risk of congenital malformation (odds ratio [OR] 1.19, 95% confidence interval [CI] 0.96-1.46, P = 0.106) or a small for gestational age (SGA) infant (OR 1.99, 95% CI 0.78-5.1, P = 0.152) compared to no exposure. However, exposure to a GABA analog was associated with an increased risk of preterm birth (PB) (OR 1.56, 95% CI 1.04-2.35, P = 0.033), spontaneous abortion (SA) (OR 1.64, 95% CI 1.14-2.38, P = 0.008), or termination of pregnancy (TOP) (OR 3.02, 95% CI 2-4.56, P < 0.001). CONCLUSION: Exposure to GABA analogs during pregnancy does not appear to be associated with congenital malformation, although there was some evidence of a higher risk of several other negative neonatal outcomes. Given the few studies included, larger prospective studies controlling for important confounders are needed to verify our findings.


Assuntos
Nascimento Prematuro , Estudos de Coortes , Feminino , Humanos , Lactente , Recém-Nascido , Gravidez , Resultado da Gravidez , Nascimento Prematuro/induzido quimicamente , Nascimento Prematuro/epidemiologia , Estudos Prospectivos , Ácido gama-Aminobutírico/efeitos adversos
12.
Chem Biodivers ; 19(9): e202200609, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35997664

RESUMO

Eleven new seco-iridoids, valeridoids G-Q (1-6 and 8-12), along with four known products, 9-epi-valtral C (7), desacylbaldrinal (13), 11-methoxyviburtinal (14) and baldrinal (15), were obtained from Valeriana jatamansi. Among them, the new compounds were identified by their NMR, HR-ESI-MS spectroscopic data and ECD calculation. Moreover, valeridoid N and O were a pair of C3 epimers, whose ether bonds between C-1 and C-3 opened, and new ether bonds formed between C-3 and C-6. Valeridoid Q belonged to the C-1 degradation of seco-iridoids. As a result, 9-epi-valtral C displayed significant inhibition on Streptococcus agalactiae, Staphylococcus aureus, Staphylococcus argenteus, Shigella flexneri and Klebsiella pneumoniae, and valeridoid Q exhibited the most significant inhibition against Salmonella enteritidis. 9-Epi-valtral C and baldrinal selectively inhibited the growth of human glioma stem cells. Valeridoid Q exhibited significant anti-influenza activity, while valeridoid O inhibited nitric oxide production.


Assuntos
Valeriana , Éteres , Humanos , Iridoides/química , Estrutura Molecular , Óxido Nítrico , Raízes de Plantas/química , Valeriana/química
13.
Neuro Endocrinol Lett ; 43(1): 18-26, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35786806

RESUMO

OBJECTIVES: This study aimed to investigate the role of estrogen in the differential diagnosis of depression and schizophrenia and its relationship with the curative effects, adverse events. METHODS: From 2017 to 2019, patients with depression or schizophrenia treated with modern electroconvulsive therapy (MECT) were studied retrospectively. Their serum estrogen levels, Hamilton Depression Scale, and Brief Psychiatric Rating Scale scores were collected. Differences in the estrogen levels between patients with depression and schizophrenia before and after treatment and the correlation of the estrogen level with curative effect and adverse events was evaluated. In total, 67 patients with depression and 61 with schizophrenia were included. RESULTS: There were no significant differences in the baseline characteristics, except the estrogen level (p < 0.001). Serum estrogen levels increased in both groups after MECT (117 vs. 141 pmol/L, p < 0.001; 42 vs. 46 pmol/L, respectively; p < 0.001), and higher estrogen levels were positively correlated with better outcomes (p < 0.001). CONCLUSION: Post-MECT estrogen levels were not associated with the incidence rate of adverse events of MECT. Estrogen plays a promising role in distinguishing depression and schizophrenia and evaluating the therapeutic efficacy of MECT.


Assuntos
Eletroconvulsoterapia , Esquizofrenia , Depressão/diagnóstico , Estrogênios , Humanos , Julgamento , Prognóstico , Estudos Retrospectivos , Esquizofrenia/diagnóstico , Esquizofrenia/terapia
14.
Oxid Med Cell Longev ; 2022: 9069825, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35855863

RESUMO

Ferroptosis is a regulated cell death that characterizes the lethal lipid peroxidation and iron overload, which may contribute to early brain injury (EBI) pathogenesis after subarachnoid hemorrhage (SAH). Although Sirtuin 1 (SIRT1), a class III histone deacetylase, has been proved to have endogenous neuroprotective effects on the EBI following SAH, the role of SIRT1 in ferroptosis has not been studied. Hence, we designed the current study to determine the role of ferroptosis in the EBI and explore the correlation between SIRT1 and ferroptosis after SAH. The pathways of ferroptosis were examined after experimental SAH in vivo (prechiasmatic cistern injection mouse model) and in HT-22 cells stimulated by oxyhemoglobin (oxyHb) in vitro. Then, ferrostatin-1 (Fer-1) was used further to determine the role of ferroptosis in EBI. Finally, we explored the correlation between SIRT1 and ferroptosis via regulating the expression of SIRT1 by resveratrol (RSV) and selisistat (SEL). Our results showed that ferroptosis was involved in the pathogenesis of EBI after SAH through multiple pathways, including acyl-CoA synthetase long-chain family member 4 (ACSL4) activation, iron metabolism disturbance, and the downregulation of glutathione peroxidase 4 (GPX4) and ferroptosis suppressor protein 1 (FSP1). Inhibition of ferroptosis by Fer-1 significantly alleviated oxidative stress-mediated brain injury. SIRT1 activation could suppress SAH-induced ferroptosis by upregulating the expression of GPX4 and FSP1. Therefore, ferroptosis could be a potential therapeutic target for SAH, and SIRT1 activation is a promising method to inhibit ferroptosis.


Assuntos
Lesões Encefálicas , Ferroptose , Sirtuína 1 , Hemorragia Subaracnóidea , Animais , Lesões Encefálicas/metabolismo , Camundongos , Sirtuína 1/metabolismo , Hemorragia Subaracnóidea/metabolismo
15.
Front Physiol ; 13: 845087, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35250643

RESUMO

Polyphagous Apolygus lucorum has become the dominant insect in Bacillus thuringiensis (Bt) cotton fields. Hormone 20-hydroxyecdysone (20E) regulates multiple insect development and physiology events. 20E responses are controlled by pathways triggered by phospholipase C (PLC)-associated proteins. However, 20E-modulated genes and related proteins that can be affected by PLC still remain unknown. Here, isobaric tag for relative and absolute quantitation (iTRAQ) and immunoblotting techniques were used to compare differentially expressed proteins (DEPs) in A. lucorum in response to the treatment of 20E and the PLC inhibitor U73122 as well as their combination. A total of 1,624 non-redundant proteins and 97, 248, 266 DEPs were identified in the 20E/control, U73122/control, and 20E + U73122/control groups, respectively. Only 8 DEPs, including pathogenesis-related protein 5-like, cuticle protein 19.8, trans-sialidase, larval cuticle protein A2B-like, cathepsin L1, hemolymph juvenile hormone-binding protein, ATP-dependent RNA helicase p62-like, and myosin-9 isoform X1, were detected in all three groups. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that the DEPs were involved in diverse signaling pathways. The results were validated by immunoblotting, which highlighted the reliability of proteomics analysis. These findings provided novel insights into the function of PLC in 20E signaling pathway in A. lucorum.

16.
Parasite Immunol ; 43(12): e12893, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34637545

RESUMO

Toxoplasma gondii (T. gondii) is a neurotropic protozoan parasite, which can cause mental and behavioural disorders. The present study aimed to elucidate the effects and underlying molecular mechanisms of sertraline (SERT) on T. gondii-induced depression-like behaviours. In the present study, a mouse model and a microglial cell line (BV2 cells) model were established by infecting with the T. gondii RH strain. In in vivo and in vitro experiments, the underlying molecular mechanisms of SERT in inhibiting depression-like behaviours and cellular perturbations caused by T. gondii infection were investigated in the mouse brain and BV2 cells. The administration of SERT significantly ameliorated depression-like behaviours in T. gondii-infected mice. Furthermore, SERT inhibited T. gondii proliferation. Treatment with SERT significantly inhibited the activation of microglia and decreased levels of pro-inflammatory cytokines such as tumour necrosis factor-alpha, and interferon-gamma, by down-regulating tumour necrosis factor receptor 1/nuclear factor-kappa B signalling pathway, thereby ameliorating the depression-like behaviours induced by T. gondii infection. Our study provides insight into the underlying molecular mechanisms of the newly discovered role of SERT against T. gondii-induced depression-like behaviours.


Assuntos
Toxoplasma , Toxoplasmose , Animais , Depressão/tratamento farmacológico , Camundongos , Microglia/metabolismo , Microglia/parasitologia , Sertralina/metabolismo , Sertralina/farmacologia , Toxoplasma/fisiologia , Toxoplasmose/tratamento farmacológico , Toxoplasmose/metabolismo
17.
Transl Oncol ; 14(12): 101214, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34500231

RESUMO

P-glycoprotein (P-gp) acts as a pump to transport cytotoxic drugs out of cells and is upregulated in cancer cells. Suppressing the expression of P-gp is an effective strategy to overcome multidrug resistance in cancer chemotherapy. Temozolomide (TMZ) is the recommended drug for the standard treatment of patients with glioblastoma, but its clinical application is restricted due to drug resistance. Transient receptor potential channel-5 (TRPC5), a Ca2+-permeable channel, has been attributed to a different drug resistance mechanism except DNA repair system; therefore, we aimed to elucidate the mechanism regarding the role of TRPC5 in TMZ resistance. TRPC5 and P-glycoprotein (P-gp) are upregulated in TMZ-resistant glioblastoma cell lines. The downregulation of TRPC5 inhibited P-gp expression and led to a significant reversal of TMZ resistance in TMZ-resistant cell lines. TRPC5-siRNA restricted the growth of tumour xenografts in an athymic nude mouse model of TMZ-resistant cells. In specimens from patients with recurrent glioblastoma, TRPC5 was found to be highly expressed, accompanied by the upregulation of P-gp expression. The nuclear factor of activated T cell isoform c3 (NFATc3), which acts as a transcriptional factor, bridges TRPC5 activity to P-gp induction. In conclusion, these results demonstrate the functional role of the TRPC5-NFATc3-P-gp signalling pathway in TMZ resistance in glioblastoma cells.

18.
Eur J Pharmacol ; 910: 174497, 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34508751

RESUMO

Toxoplasma gondii (T. gondii) is an obligate intracellular parasite that can cause liver diseases in the host, including hepatitis and hepatomegaly. High mobility group box 1 (HMGB1) is the main inflammatory mediator causing cell injury or necrosis. HMGB1 binds to toll like receptor 4 (TLR4), then activates the nuclear factor-κB (NF-κB) signaling pathway, which promotes the release of inflammatory factors. Our previous studies showed that HMGB1 mediated TLR4/NF-κB signaling pathway plays an important role in liver injury induced by T. gondii infection. Resveratrol (RSV) is a small polyphenol, which has anti-inflammatory, anti-cancer, anti-T. gondii effect. However, the effect of RSV on liver injury caused by T. gondii infection is unclear. This study used the RH strain tachyzoites of T. gondii to infect murine liver line, NCTC-1469 cells to establish an in vitro model and acute infection of mice for the in vivo model to explore the protective effect of RSV on liver injury induced by T. gondii infection. The results showed that RSV inhibited the proliferation of T. gondii in the liver, reduced the alanine aminotransferase/aspartate aminotransferase levels and pathological liver damage. Additionally, RSV inhibited the production of tumor necrosis factor-α, inducible nitric oxide synthase and HMGB1 by interfering with the TLR4/NF-κB signaling pathway. These results indicate that RSV can protect liver injury caused by T. gondii infection by intervening in the HMGB1/TLR4/NF-κB signaling pathway. This study will provide a theoretical basis for RSV treatment of T. gondii infection induced liver injury.


Assuntos
Hepatite Animal/prevenção & controle , Fígado/efeitos dos fármacos , Resveratrol/farmacologia , Toxoplasmose/complicações , Animais , Linhagem Celular , Modelos Animais de Doenças , Feminino , Proteína HMGB1/metabolismo , Hepatite Animal/imunologia , Hepatite Animal/parasitologia , Hepatite Animal/patologia , Hepatócitos/efeitos dos fármacos , Hepatócitos/imunologia , Hepatócitos/patologia , Humanos , Fígado/citologia , Fígado/imunologia , Fígado/patologia , Camundongos , NF-kappa B/metabolismo , Resveratrol/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia , Receptor 4 Toll-Like/metabolismo , Toxoplasmose/tratamento farmacológico , Toxoplasmose/imunologia , Toxoplasmose/parasitologia
19.
Int J Clin Pract ; 75(7): e14225, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33871134

RESUMO

STUDY OBJECTIVES: In this study, we conducted a cross-sectional analysis of the sleep characteristics in the elderly Chinese people to comprehensively investigate the association between sleep and cognitive function in the elderly people. We aimed to evaluate the most important demographic factors, conventional physiological indices and living habits that may influence sleep. METHODS: We surveyed 2901 elderly people (age ≥60 years old) face-to-face from 1 July to 31 December 2017, who were recruited from 17 communities of the Pudong New Area (Shanghai, China) by probability proportional to size. The Pittsburgh sleep quality index (PSQI) scale was used to describe the sleep features of each participant. Cognitive assessment was performed using the mini-mental state examination (MMSE) scale, Montreal cognitive assessment (MoCA) and the clinical dementia rating (CDR) scale. Those factors which potentially influence sleep and consequentially may impact cognition in the elderly people were evaluated, and the correlations of sleep characteristics and cognitive function were explored by the linear regression analysis. RESULTS: Altogether, there were 1287 (44.4%) people taking part in the investigation. Sleep quality was significantly correlated with MMSE and MoCA total scores. Healthy sleep (especially enough sleep) was correlated with better cognitive functions. Besides recognised relative factors (such as age, sex and living alone), the number of children was found to be a strong risk factor of poor sleep. Anxiety before sleep and light/noise interference significantly damaged sleep while an exercise routine was associated with better sleep. Moderate levels of reading, watching TV and household work were correlated with superior sleep quality. CONCLUSION: In conclusion, sleep characteristics correlate with cognitive decline in the elderly people, and they can be influenced by multiple demographic factors and living habits. To improve sleep quality, it may be important to change sleep environment, to be relax, to increase physical exercise and recreational activities moderately.


Assuntos
Disfunção Cognitiva , Idoso , Criança , China/epidemiologia , Disfunção Cognitiva/epidemiologia , Estudos Transversais , Humanos , Testes de Estado Mental e Demência , Pessoa de Meia-Idade , Sono
20.
Phytochemistry ; 184: 112681, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33548771

RESUMO

Seven undescribed (valejatadoids A-G) and 26 known iridoids were obtained from the roots and rhizomes of Valeriana jatamansi. Their structures were determined based on extensive spectroscopic data, especially 1D and 2D NMR, along with HRESIMS. Valejatadoid B is a monoene-type iridoid with a unique double bond between C-4 and C-5. Valejatadoids D-G, jatamanin U, jatamanin O, jatamanvaltrate E, valeriotetrate C, IVHD-valtrate, 10-isovaleroxy-valtrathydrin, jatamanvaltrate Q, valeriandoid F, jatamanvaltrate K, jatamanvaltrate W and isovaltrate were more potent than the positive control when evaluated for inhibition of NO production. Among them, valeriandoid F and jatamanvaltrate K exhibited the most significant inhibitory effects with IC50 values of 0.88 and 0.62 µM, respectively. In addition, valeriandoid F selectively inhibited the proliferation of human glioma stem cell lines, GSC-3# and GSC-18#, with IC50 values of 7.16 and 5.75 µM, respectively.


Assuntos
Nardostachys , Valeriana , Anti-Inflamatórios , Iridoides/farmacologia , Estrutura Molecular , Raízes de Plantas
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