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1.
Behav Brain Res ; : 113000, 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33161032

RESUMO

A large body of literature has demonstrated that prenatal stress (PS) can induce depression-like behavior in the offspring. However, the underlying mechanism remains largely unknown. CREB-regulated transcriptional coactivator 1(CRTC1) has recently been shown to involve in mood regulation. This research aims to investigate whether CRTC1 signaling was involved in the depression-like behavior of prenatally stressed offspring rats. Sucrose preference test (SPT), forced swimming test (FST) and open field test (OFT) were adopted to test the depression-like behavior in the male offspring rats, and CRTC1 signaling was measured. The results showed that there were significantly reduced sucrose intake in SPT and prolonged immobility time in FST in PS-exposure offspring rats. It was also found decreased levels of total CRTC1, nuclear CRTC1, calcineurin, brain-derived neurotrophic factor (BDNF) and c-fos, but increased cytoplasmic p-CRTC1 in the hippocampus (HIP) and prefrontal cortex (PFC) of the offspring rats. Furthermore, the mRNA level of CRTC1, calcineurin, BDNF, c-fos were down-regulated. Abnormal expression of CRTC1 signaling could be alleviated by fluoxetine treatment. In conclusion, our research indicated that the aberration of CRTC1 expression and/or phosphorylation activity might play a vital role in PS-induced depression-like behavior of offspring rats.

2.
Huan Jing Ke Xue ; 41(8): 3601-3611, 2020 Aug 08.
Artigo em Chinês | MEDLINE | ID: mdl-33124333

RESUMO

To determine the reasons for the variation in the vertical distribution of nitrogen in sediment interstitial waters between different stratified reservoirs, the characteristics of overlying water-interstitial water in Xiangxi Bay, Yangtze River mainstream, and Xiaowan Reservoir were monitored. The vertical distribution of nitrogen in sediment interstitial waters in these different stratified waters were then analyzed, and the reasons for the variation in this distribution were assessed. The results showed:① the ρ(TN) in the sediment interstitial waters of the Yangtze River mainstream and Xiangxi Bay gradually increased with depth, while that of Xiaowan Reservoir reached its maximum at 12 cm and the bottom layer presented a "C" distribution. The ρ(NH4+) in the sediment interstitial waters of the Yangtze River mainstream and Xiangxi Bay exhibited an increasing trend with depth, while that of Xiaowan Reservoir was slightly higher in the bottom layer than in the surface layer, although the change with depth was not significant. Overall, the ρ(NH4+) in the sediment interstitial waters of the Yangtze River mainstream and Xiangxi Bay was higher than that of Xiaowan Reservoir, and the concentration ranges were as follows:0.512-8.289 mg·L-1, 0.968-9.307 mg·L-1, and 0.950-1.450 mg·L-1. The vertical distribution of the ρ(NO3-) in the sediment interstitial waters of all three waterbodies were opposite to that of ρ(NH4+). Moreover, the ρ(NO3-) in the sediment interstitial waters of Xiangxi Bay and the Yangtze River mainstream was higher than that of Xiaowan Reservoir. The concentration ranges were as follows:0.143-0.674 mg·L-1, 0.107-0.647 mg·L-1, and 0.050-0.051 mg·L-1. ② There were also significant differences in the vertical distribution of physical and chemical indices in the three water bodies. There was no significant change in the vertical distribution of the water temperature in the Yangtze River mainstream and the N2 value was <5×10-5 s-2; hence, the water was well mixed, and the vertical range of the dissolved oxygen content was 6.180-6.318 mg·L-1. The water temperature in the upper and middle reaches of Xiangxi Bay decreased vertically, while the water temperature in the lower reach presented a ladder-like distribution and the N2 values were all>5×10-5 s-2; thus, the water was in a stable stratified state and the dissolved oxygen content presented a "C" distribution. There was obvious stratification at the depths of 5-15 m and 54-70 m in Xiaowan Reservoir. The dissolved oxygen content decreased significantly at higher water temperature gradients, and there was no significant change along the water depth below 80 m. ③ The main reasons for the variation in the vertical distribution of nitrogen in the sediment interstitial waters of the three waterbodies were the differences in the overlying water hydrodynamics, dissolved oxygen distribution, and sediment environment. The ρ(NH4+) and ρ(NO3-) were higher in Xiangxi Bay, which may have increased the denitrification rate and subsequently have helped to remove nitrogen and reduce the nitrogen load in these waters.

3.
Mol Cancer Ther ; 19(12): 2465-2475, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33087507

RESUMO

The purpose of this study was to determine if radiation (RT)-resistant cervical cancers are dependent upon glutamine metabolism driven by activation of the PI3K pathway and test whether PI3K pathway mutation predicts radiosensitization by inhibition of glutamine metabolism. Cervical cancer cell lines with and without PI3K pathway mutations, including SiHa and SiHa PTEN-/- cells engineered by CRISPR/Cas9, were used for mechanistic studies performed in vitro in the presence and absence of glutamine starvation and the glutaminase inhibitor, telaglenastat (CB-839). These studies included cell survival, proliferation, quantification of oxidative stress parameters, metabolic tracing with stable isotope-labeled substrates, metabolic rescue, and combination studies with L-buthionine sulfoximine (BSO), auranofin (AUR), and RT. In vivo studies of telaglenastat ± RT were performed using CaSki and SiHa xenografts grown in immune-compromised mice. PI3K-activated cervical cancer cells were selectively sensitive to glutamine deprivation through a mechanism that included thiol-mediated oxidative stress. Telaglenastat treatment decreased total glutathione pools, increased the percent glutathione disulfide, and caused clonogenic cell killing that was reversed by treatment with the thiol antioxidant, N-acetylcysteine. Telaglenastat also sensitized cells to killing by glutathione depletion with BSO, thioredoxin reductase inhibition with AUR, and RT. Glutamine-dependent PI3K-activated cervical cancer xenografts were sensitive to telaglenastat monotherapy, and telaglenastat selectively radiosensitized cervical cancer cells in vitro and in vivo These novel preclinical data support the utility of telaglenastat for glutamine-dependent radioresistant cervical cancers and demonstrate that PI3K pathway mutations may be used as a predictive biomarker for telaglenastat sensitivity.

4.
Medicine (Baltimore) ; 99(31): e20972, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32756084

RESUMO

BACKGROUND: Home-based cardiac rehabilitation is considered as an alternative strategy of cardiac rehabilitation, aims to enhance patients participation rate. Since it emphasizes patients subjective initiative, patients require a better understanding of their illness and manage their conditions. We perform this systematic review and meta-analysis to identify the role and effectiveness of the self-management program in home-based cardiac rehabilitation. METHOD: We conduct the search strategy from an online database: PubMed, web of science, CINAL, EMBASE, OVID/Medline, and google scholar. Studies meet the inclusion criterion and published in the English language in recent 10 years will be screened by 2 independent reviewers. Then they extract data and assess the risk of bias. The disagreement between them will be resolved by the third reviewer. Data analysis is performed by Review Manager (Version 5.3). RESULT: This is systematic review and meta-analysis will identify the role of self-management in home-based cardiac rehabilitation program and evaluate its effectiveness. CONCLUSION: The findings of this study will be published in a related peer-reviewed journal.Protocol registration number: INPLASY202050093.


Assuntos
Reabilitação Cardíaca , Serviços de Assistência Domiciliar , Autogestão , Reabilitação Cardíaca/métodos , Humanos , Avaliação de Programas e Projetos de Saúde , Autogestão/métodos
5.
Medicine (Baltimore) ; 99(31): e21485, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32756176

RESUMO

BACKGROUND: Exercise intolerance is very common in patients with coronary heart disease (CHD). Although some researches confirming the validation of traditional Chinese medicine (TCM) on CHD treatment, the effect of TCM on improving the exercise tolerance of patients with CHD remains unclear so far. Our trial is to investigate whether the Yangxinshi (YXS) tablet can improve exercise tolerance as well as the quality of life among CHD patients. METHODS: It is a randomized, double-blind, placebo-controlled, multi-center trial. A total of 90 patients with CHD from 3 hospitals in China will be enrolled and randomly assigned to one of 2 groups: YXS group, N = 45; placebo group, N = 45. The 2 groups will simultaneously receive standardized western medicine and exercise-based cardiac rehabilitation program for 12 weeks. The primary outcome measure is the exercise capacity, which will be evaluated by the cardiopulmonary exercise test and 6-minute walking test. The 2nd outcomes include symptom improvement, psychologic issues, laboratory tests, side effects, and adverse events. DISCUSSION: To our knowledge, it is the 1st randomized controlled trial to evaluate the effect of TCM YXS tablet on exercise tolerance in patients with CHD. The results will provide more evidence for future studies in this area. TRIAL REGISTRATION: This study protocol was registered in Research Registry (researchregistry5752).


Assuntos
Doença das Coronárias/terapia , Medicamentos de Ervas Chinesas/administração & dosagem , Tolerância ao Exercício/efeitos dos fármacos , Medicina Tradicional Chinesa/métodos , Adulto , Idoso , China , Doença das Coronárias/fisiopatologia , Método Duplo-Cego , Teste de Esforço , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Teste de Caminhada
6.
Helicobacter ; 25(5): e12749, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32770644

RESUMO

BACKGROUND: Limited research has been published on the recurrence of Helicobacter pylori infection and risk factors in Chinese children. Our study aimed to identify risk factors for Helicobacter pylori infection recurrence after successful eradication in children. MATERIALS AND METHODS: A prospective, nested case-control study was performed. A cohort of 230 children with successful eradication of Helicobacter pylori in Baoding (China) was selected from January 2018 to February 2019. A standardized questionnaire was used to obtain socioeconomic details. Eradication regimens and Helicobacter pylori antibiotic susceptibility testing results were also recorded. Interleukin-1ß level, interferon-γ level, and genetic susceptibility (IFNGR1 and PTPRZ1 gene polymorphisms) were analyzed. All children were followed for 1 year. RESULTS: Among 218 (94.8%) children who were successfully followed, 41 children (18.8%) had a Helicobacter pylori infection recurrence. The recurrence rate was higher in children ≤10 years old than >10 years old (22.8% vs 7.1%, P = .01). There was no significant difference between the recurrence group and the non-recurrence group in terms of types of therapy and antibiotic sensitivity (P > .05). Multivariable regression results indicated that residence in urban areas, higher household income, and having lunch at home were significantly protective against recurrence (OR 0.155, 0.408, and 0.351 respectively), whereas Helicobacter pylori infection in family members increased the risk of recurrence (OR 2.283). The levels of IL-1ß and IFN-γ exhibited no significant difference between the recurrence group and the non-recurrence group. The allele frequency of G in the IFNGR1-56 site, A in the IFNGR1-600 site, and T in the IFNGR1-565 site was significantly higher in the recurrence group when compared to the non-recurrence group (P < .05). CONCLUSIONS: The Helicobacter pylori infection recurrence rate is high in children in Baoding region and is closely correlated to socioeconomic factors. The IFNGR1 gene polymorphism may be an independent risk factor for Helicobacter pylori infection recurrence.

7.
J Environ Manage ; 274: 111197, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32798850

RESUMO

The Lancang River in China is the headwater of the Mekong River. The impacts of reservoirs on the water, sediment and nutrient trapping in the Lancang River have attracted considerable attention, both locally and abroad. In this research, watershed-scale nitrogen load and nitrate sources along the Lancang River upstream in free-flowing reaches (FFRs) and downstream regulated reaches (RRs) were analyzed using stable nitrogen and oxygen isotopes. The results showed that the nitrogen nutrient (TN, NO3- and NH4+) concentration increased from upstream to downstream along the Lancang River, and the highest values come from large-scale urban samples rather than the reservoirs. Compared to other large rivers in China, such as the Yangtze River, Yellow River and Yalu Tsangpo River, nitrogen nutrient content in the Lancang River is at low level. The nitrate concentration ranged from 0.14 mg/L to 0.63mg/Land increased significantly downstream. The isotopic values ranged from 2.8‰ to 5.2‰ for δ15N-NO3- and from 4‰ to 8.5‰ for δ18O-NO3- along the river, and the δ15N-NO3- value rose significantly downstream. According to the nitrogen and oxygen isotope approach, soil organic nitrogen mineralization was the main source of the nitrate with an average of 51% contribution; domestic sewage was the second largest contributor with an average of 33% but increase downstream, likely due to the significantly larger population in the downstream region. Furthermore, the nitrate concentration decreased and δ15N- and δ18O-NO3- enriched in the Nuozhadu reservoir, indicating that the reservoir may enhance nitrate consumption and reduce nitrogen pollution to downstream reaches. The results provide a perspective of nitrogen nutrient for the trans-border river management and more insight researches are called for understanding the controversial nutrient transport topic in this region.


Assuntos
Nitrogênio/análise , Poluentes Químicos da Água/análise , China , Monitoramento Ambiental , Nitratos/análise , Isótopos de Nitrogênio/análise , Isótopos de Oxigênio/análise
8.
J Pharm Sci ; 109(11): 3300-3307, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32721471

RESUMO

Polysorbates (PS) are surfactants commonly added in a therapeutic protein drug product to protect proteins from denaturation and aggregation during storage, transportation, and delivery. Significant degradation of PS in drug products could lead to particulate formation with shortened drug shelf life, and one of the major root causes of PS degradation is the host cell protein (HCP) derived lipase/esterase, which belong to the serine hydrolase family. Typically, PS degradation can only be observed in drug products after a long time of storage if very low levels of host cell protein impurity with PS degradation activities are present. In this study, PS80 degradation was observed in a monoclonal antibody (mAb) within 18 h at 5 °C with a low level of HCP presented (<20 ppm) based on ELISA quantitation. This observation suggested that a trace amount of unknown host cell protein(s) with strong enzymatic activity on polysorbate degradation was present in this drug substance. The activity-based protein profiling (ABPP) method with the ActivX FP serine hydrolase probe was employed to identify host cell proteins that can hydrolyze PS. Two hydrolases, liver carboxylesterase B-1-like protein (CES-B1L, A0A061I7X9) and liver carboxylesterase 1-like protein (CES-1L, A0A061IFE2) were identified with high confidence using the ABPP approach for the first time in a mAb drug substance during early stage development. PS80 became stable in the drug substance sample after the two hydrolases were depleted using the immobilized ActivX FP probe, confirming these two hydrolases were responsible for the rapid PS80 degradation. In addition, the PS80 degradation pattern was found to be equivalent to that generated by their human analog, human liver carboxylesterase-1 (hCES-1) and rabbit liver esterase (rLES). Overall, these results suggest that CES-B1L and CES-1L are the primary cause of PS80 degradation in this mAb drug.

9.
Anal Chem ; 92(17): 11573-11581, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32614575

RESUMO

Annotation of untargeted high-resolution full-scan LC-MS metabolomics data remains challenging due to individual metabolites generating multiple LC-MS peaks arising from isotopes, adducts, and fragments. Adduct annotation is a particular challenge, as the same mass difference between peaks can arise from adduct formation, fragmentation, or different biological species. To address this, here we describe a buffer modification workflow (BMW) in which the same sample is run by LC-MS in both liquid chromatography solvent with 14NH3-acetate buffer and in solvent with the buffer modified with 15NH3-formate. Buffer switching results in characteristic mass and signal intensity changes for adduct peaks, facilitating their annotation. This relatively simple and convenient chromatography modification annotated yeast metabolomics data with similar effectiveness to growing the yeast in isotope-labeled media. Application to mouse liver data annotated both known metabolite and known adduct peaks with 95% accuracy. Overall, it identified 26% of ∼27 000 liver LC-MS features as putative metabolites, of which ∼2600 showed HMDB or KEGG database formula match. This workflow is well suited to biological samples that cannot be readily isotope labeled, including plants, mammalian tissues, and tumors.

10.
Neural Plast ; 2020: 9436406, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32684926

RESUMO

Most previous imaging studies have used traditional Pearson correlation analysis to construct brain networks. This approach fails to adequately and completely account for the interaction between adjacent brain regions. In this study, we used the L1-norm linear regression model to test the small-world attributes of the brain networks of three groups of patients, namely, those with mild cognitive impairment (MCI), Alzheimer's disease (AD), and healthy controls (HCs); we attempted to identify the method that may detect minor differences in MCI and AD patients. Twenty-four AD patients, 33 MCI patients, and 27 HC elderly subjects were subjected to functional MRI (fMRI). We applied traditional Pearson correlation and the L1-norm to construct the brain networks and then tested the small-world attributes by calculating the following parameters: clustering coefficient (Cp), path length (Lp), global efficiency (Eg), and local efficiency (Eloc). As expected, L1 could detect slight changes, mainly in MCI patients expressing higher Cp and Eloc; however, no statistical differences were found between MCI patients and HCs in terms of Cp, Lp, Eg, and Eloc, using Pearson correlation. Compared with HCs, AD patients expressed a lower Cp, Eloc, and Lp and an increased Eg using both connectivity metrics. The statistical differences between the groups indicated the brain networks constructed by the L1-norm were more sensitive to detect slight small-world network changes in early stages of AD.

11.
Medicine (Baltimore) ; 99(27): e21062, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32629734

RESUMO

BACKGROUND: The benefits of high-intensity interval training (HIIT) are well-known, there is insufficient evidence about the effects of HIIT on heart failure with preserved ejection fraction (HFpEF). METHOD: Multiple databases include MEDLINE, PubMed, EMBASE, CINAHL, Web of Science, PEDro, Cochrane Library, and Google Scholar are used to search for randomized controlled trials investigating the effects of HIIT on HFpEF. All related articles published with the English language with no time limitation will be included. Two reviews independently conducted the selection, data extraction, and quality assessment. The primary outcome is exercise capacity. The secondary outcomes include quality of life (QoL), blood pressure (BP), ventricular function, and left ventricular diastolic function, symptom improvement, endothelial function, and arterial stiffness. Data analysis is performed with Review Manager Software (Version 5.3). RESULT: This systematic review and meta-analysis aim to evaluate the efficacy of HIIT on HFpEF, its outcome will provide reliable evidence for future studies. CONCLUSION: The findings of this study will be published in a related peer-reviewed journal. REGISTRATION NUMBER: INPLASY202050097.


Assuntos
Insuficiência Cardíaca/reabilitação , Treinamento Intervalado de Alta Intensidade/métodos , Volume Sistólico/fisiologia , Pressão Sanguínea/fisiologia , Diástole/fisiologia , Endotélio Vascular/fisiologia , Estudos de Avaliação como Assunto , Tolerância ao Exercício/fisiologia , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/psicologia , Humanos , Qualidade de Vida/psicologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Rigidez Vascular/fisiologia , Função Ventricular Esquerda/fisiologia
12.
J Pharm Sci ; 109(9): 2710-2718, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32534029

RESUMO

Polysorbates (PS) are surfactants commonly added in a therapeutic protein drug product as excipients to protect proteins from denaturation and aggregation during storage, transportation, and delivery. Significant degradation of PS in drug products could lead to shortened drug shelf lives and PS-degrading activity in drug products must be minimized. Identification of lipases that degrade PS could lead to better process control in drug manufacturing. In 2016, phospholipase B-like 2 (PLBD2) was proposed as a residual host cell protein responsible for degrading PS20 in a drug formulation. We have carried out a series of studies to verify the role of PLBD2 in degrading polysorbates in drug products purified from recombinant Chinese Hamster Ovary (CHO) cells. Genetic knock-out and immuno-depletion results showed that when PLBD2 was removed or depleted, the degradation of PS20 or PS80 was neither diminished nor reduced. In addition, a quantitative analysis of PLBD2 and PS20 degradation in multiple formulated mAb products did not establish a correlation between the amount of PLBD2 and the level of PS20 degradation. Collectively these results suggest that PLBD2 is not the primary cause of polysorbate degradation in formulated drug products purified using standard Protein A and ion exchange chromatography.

13.
Front Microbiol ; 11: 1117, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32582081

RESUMO

Background: Vaginal candidiasis is an important medical condition awaiting more effective treatment. How Candida albicans causes this disease and survives antifungal treatment is not yet fully understood. This study aimed to establish a comprehensive understanding of biofilm-related defensive strategies that C. albicans uses to establish vaginal candidiasis and to survive antifungal treatment. Methods: A mouse model of vaginal candidiasis was adopted to examine the formation of biotic biofilms on the vaginal epithelium and fungal infiltration by laboratory and clinical strains of C. albicans. Histopathological changes and local inflammation in the vaginal epithelium caused by C. albicans of different biofilm phenotypes were compared. Antifungal susceptibility testing was carried out for C. albicans grown as planktonic cells, microplate-based abiotic biofilms, and epithelium-based biotic biofilms. Formation of persister cells by C. albicans in different growth modes was also quantified and compared. Results: C. albicans wild-type reference strains and clinical isolates, but not the biofilm-defective mutants, formed a significant number of biotic biofilms on the vaginal epithelium of mice and infiltrated the epithelium. Biofilm formation and epithelial invasion induced local inflammatory responses and histopathological changes in the vaginal epithelium including neutrophil infiltration and subcorneal microabscesses. Biofilm growth on the vaginal epithelium also led to high resistance to antifungal treatments and promoted the formation of antifungal-tolerant persister cells. Conclusion: This study comprehensively assessed biofilm-related microbial strategies that C. albicans uses in vaginal candidiasis and provided experimental evidence to support the important role of biofilm formation in the histopathogenesis of vaginal candidiasis and the recalcitrance of the infection to antifungal treatment.

14.
Ear Nose Throat J ; : 145561320925327, 2020 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-32383982

RESUMO

OBJECTIVES: To explore the diagnostic value and pathological correlation of narrow band imaging (NBI) classification in laryngeal lesions. METHODS: A total of 112 patients (123 lesions) with laryngeal lesions from July 2018 to May 2019 were selected in this study. All patients were examined by NBI and white light imaging endoscopy. The NBI endoscopy was applied to classify the observed lesion sites according to intraepithelial papillary capillary loop pattern. The gold standard of diagnosis was pathological results. To evaluate the consistency of NBI classification and pathological results. RESULTS: The sensitivity, specificity, positive predictive value, and negative predictive value of the diagnosis for benign, precancerous, and malignant lesions under the NBI endoscopy were 90.91%, 81.19%, 74.07%, 85.42%; 41.67%, 92.93%, 58.82%, 86.79%; and 93.51%, 65.22%, 91.14%, 68.18%, respectively. There was a high consistency between NBI classification and pathological results (κ = 0.679, P < .001). CONCLUSIONS: The NBI classification can improve the accuracy of the diagnosis of laryngeal lesions. It is important for early diagnosis and treatment of vocal cord leukoplakia and laryngeal cancer.

15.
PLoS Genet ; 16(5): e1008772, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32365064

RESUMO

In the postgenomics era, comparative genomics have advanced the understanding of evolutionary processes of neuropeptidergic signaling systems. The evolutionary origin of many neuropeptidergic signaling systems can be traced date back to early metazoan evolution based on the conserved sequences. Insect parathyroid hormone receptor (iPTHR) was previously described as an ortholog of vertebrate PTHR that has a well-known function in controlling bone remodeling. However, there was no sequence homologous to PTH sequence in insect genomes, leaving the iPTHR as an orphan receptor. Here, we identified the authentic ligand insect PTH (iPTH) for the iPTHR. The taxonomic distribution of iPTHR, which is lacking in Diptera and Lepidoptera, provided a lead for identifying the authentic ligand. We found that a previously described orphan ligand known as PXXXamide (where X is any amino acid) described in the cuttlefish Sepia officinalis has a similar taxonomic distribution pattern as iPTHR. Tests of this peptide, iPTH, in functional reporter assays confirmed the interaction of the ligand-receptor pair. Study of a model beetle, Tribolium castaneum, was used to investigate the function of the iPTH signaling system by RNA interference followed by RNA sequencing and phenotyping. The results suggested that the iPTH system is likely involved in the regulation of cuticle formation that culminates with a phenotype of defects in wing exoskeleton maturation at the time of adult eclosion. Moreover, RNAi of iPTHRs also led to significant reductions in egg numbers and hatching rates after parental RNAi.


Assuntos
Neuropeptídeos/metabolismo , Hormônio Paratireóideo/metabolismo , Receptores de Hormônios Paratireóideos/genética , Tribolium/anatomia & histologia , Animais , Evolução Molecular , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Fenótipo , Filogenia , Receptores de Hormônios Paratireóideos/metabolismo , Análise de Sequência de RNA , Tribolium/genética , Tribolium/metabolismo , Asas de Animais/anatomia & histologia
16.
Nat Commun ; 11(1): 2587, 2020 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-32444616

RESUMO

The gut microbiota metabolizes drugs and alters their efficacy and toxicity. Diet alters drugs, the metabolism of the microbiota, and the host. However, whether diet-triggered metabolic changes in the microbiota can alter drug responses in the host has been largely unexplored. Here we show that dietary thymidine and serine enhance 5-fluoro 2'deoxyuridine (FUdR) toxicity in C. elegans through different microbial mechanisms. Thymidine promotes microbial conversion of the prodrug FUdR into toxic 5-fluorouridine-5'-monophosphate (FUMP), leading to enhanced host death associated with mitochondrial RNA and DNA depletion, and lethal activation of autophagy. By contrast, serine does not alter FUdR metabolism. Instead, serine alters E. coli's 1C-metabolism, reduces the provision of nucleotides to the host, and exacerbates DNA toxicity and host death without mitochondrial RNA or DNA depletion; moreover, autophagy promotes survival in this condition. This work implies that diet-microbe interactions can alter the host response to drugs without altering the drug or the host.


Assuntos
Caenorhabditis elegans/efeitos dos fármacos , Floxuridina/toxicidade , Interações Alimento-Droga , Microbioma Gastrointestinal/efeitos dos fármacos , Serina/farmacologia , Animais , Caenorhabditis elegans/microbiologia , Caenorhabditis elegans/fisiologia , Suplementos Nutricionais , Escherichia coli/efeitos dos fármacos , Escherichia coli/metabolismo , Floxuridina/farmacocinética , Ácido Fólico/metabolismo , Microbioma Gastrointestinal/fisiologia , Timidina/análogos & derivados , Timidina/metabolismo , Timidina/farmacocinética , Timidina/farmacologia , Nucleotídeos de Uracila/metabolismo , Nucleotídeos de Uracila/farmacocinética
17.
Aging (Albany NY) ; 12(7): 5907-5919, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32238610

RESUMO

Numerous studies have investigated the differences in the mean functional connectivity (FC) strength between amnestic mild cognitive impairment (aMCI) patients and normal subjects using resting-state functional magnetic resonance imaging. However, whether the mean FC is increased, decreased or unchanged in aMCI patients compared to normal controls remains unclear. Two factors might lead to inconsistent results: the determination of regions of interest and the reliability of the FC.We explored differences in FC and the degree centrality (Dc) constructed by the bootstrap method, between and within networks (default-mode network (DN), frontoparietal control network (CN), dorsal attention network (AN)), and resulting from a hierarchical-clustering algorithm.The mean FC within the DN and CN was significantly increased (P < 0.05, uncorrected) in patients. Significant increases (P < 0.05, uncorrected) in the mean FC were found in patients between DN and CN and between DN and AN. Five pairs of FC (false discovery rate corrected) and the Dc of six regions (Bonferroni corrected) displayed a significant increase in patients. Lower cognitive ability was significantly associated with a greater increase in the Dc of the left superior temporal sulcus.Our results demonstrate that the early dysfunctions in aMCI disease are mainly compensatory impairments.

18.
J Cell Mol Med ; 24(8): 4480-4493, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32168416

RESUMO

Small cell lung cancer (SCLC) is a severe malignant with high morbidity; however, few effective and secure therapeutic strategy is used in current clinical practice. Oridonin is a small molecule from the traditional Chinese herb Rabdosia rubescens. This study mainly aimed to investigate the role of oridonin on inhibiting the process of H1688, a kind of small cell lung cancer cells from human. Oridonin could suppress H1688 cell proliferation and induce their apoptosis in a high dosage treatment (20 µmol/L). Meanwhile, cell migration was suppressed by oridonin (5 and 10 µmol/L) that did not affect cell proliferation and apoptosis. The expression level of E-cadherin was significantly increased, and the expression of vimentin, snail and slug was reduced after administration of oridonin. These expression changes were associated with the suppressed integrin ß1, phosphorylation of focal adhesion kinase (FAK) and ERK1/2. In addition, oridonin (5 and 10 mg/kg) inhibited tumour growth in a nude mouse model; however, HE staining revealed a certain degree of cytotoxicity in hepatic tissue after treatment oridonin (10 mg/kg). Furthermore, the concentration of alanine aminotransferase (ALP) was significantly increased and lactate dehydrogenase (LDH) was reduced after oridonin treatment (10 mg/kg). Immunohistochemical analysis further revealed that oridonin increased E-cadherin expression and reduced vimentin and phospho-FAK levels in vivo. These findings indicated that oridonin can inhibit the migration and epithelial-to-mesenchymal transition (EMT) of SCLC cells by suppressing the FAK-ERK1/2 signalling pathway. Thus, oridonin may be a new drug candidate to offer an effect of anti-SCLC with relative safety.

19.
Dalton Trans ; 49(13): 3999-4011, 2020 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-32057042

RESUMO

Efficient and low-cost catalysts for catalytic wet air oxidation (CWAO) under ambient conditions are of great significance for the degradation of hydrophobic organic contaminants. In this study, four LDH catalysts were prepared and their catalytic performance was studied by the degradation of nitrobenzene. The CuCoFe-LDH shows the best catalytic activity with an NB removal efficiency of 41.2%. The CuCoFe-LDH exhibited a typical layer structure, with a specific surface area of 167.32 m2 g-1, and Cu2+, Co2+ and Fe3+ were evenly dispersed on the crystal. The NB removal efficiency was increased by 12.5% through adding formic acid. After five recycling processes, the NB removal efficiency was 18.9% because 3.8 mg g-1 of Co was leached out of the LDH. In the CWAO process, H2O2, ˙OH, ˙O2- and 1O2 were successfully formed through activated oxygen by the CuCoFe-LDH catalyst under ambient conditions. This work further broadens the application scope of layered double hydroxides (LDHs) in the degradation of organic pollutants by CWAO under ambient conditions.

20.
FASEB J ; 34(1): 446-457, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31914682

RESUMO

Mechanical damage or infection to the endometrium can lead to the formation of adhesions in the uterine cavity, which may result in reduced reproductive outcome and/or pregnancy complications. The prognosis of this disease is poor due to few effective treatments and the complex environment of endometrium. Heparin-Poloxamer Hydrogel (HP hydrogel) is a nontoxic and biodegradable biomaterial, which has been commonly used as a sustained-release delivery system. In this study, we applied a mini-endometrial curette to scrape the endometrium of rats to mimic the process of curettage in patients. After the establishment of IUA model in rats, we injected the thermo-sensitive hydrogel(E2-HP hydrogel) into the injured uterine cavity and evaluated the therapeutic effect of E2-HP hydrogel on the recovery of IUA. Our results showed that E2-HP hydrogel can significantly facilitate the regeneration of injured endometrium along with inhibiting the cell apoptosis in IUA model. Furthermore, we revealed that E2-HP hydrogel on the recovery of IUA was closely associated with the upregulation of kisspeptin through activating the ERK1/2 and MAPKs p38 pathways. In conclusion, E2-HP hydrogel can effectively transfer E2 into the injured endometrium and it can be considered as a promising therapeutic method for the women with intrauterine adhesions.


Assuntos
Endométrio/citologia , Estradiol/farmacologia , Heparina/química , Hidrogéis/farmacologia , Poloxâmero/química , Regeneração , Aderências Teciduais/tratamento farmacológico , Útero/citologia , Animais , Endométrio/efeitos dos fármacos , Endométrio/lesões , Estradiol/química , Feminino , Hidrogéis/química , Gravidez , Ratos , Ratos Sprague-Dawley , Recuperação de Função Fisiológica , Útero/efeitos dos fármacos , Útero/lesões
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