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1.
J Exp Bot ; 75(5): 1314-1330, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38069660

RESUMO

Sphingolipids are membrane lipids and play critical roles in signal transduction. Ceramides are central components of sphingolipid metabolism that are involved in cell death. However, the mechanism of ceramides regulating cell death in plants remains unclear. Here, we found that ceramides accumulated in mitochondria of accelerated cell death 5 mutant (acd5), and expression of mitochondrion-localized ceramide kinase (ACD5) suppressed mitochondrial ceramide accumulation and the acd5 cell death phenotype. Using immuno-electron microscopy, we observed hyperaccumulation of ceramides in acer acd5 double mutants, which are characterized by mutations in both ACER (alkaline ceramidase) and ACD5 genes. The results confirmed that plants with specific ceramide accumulation exhibited localization of ceramides to mitochondria, resulting in an increase in mitochondrial reactive oxygen species production. Interestingly, when compared with the wild type, autophagy-deficient mutants showed stronger resistance to ceramide-induced cell death. Lipid profiling analysis demonstrated that plants with ceramide accumulation exhibited a significant increase in phosphatidylethanolamine levels. Furthermore, exogenous ceramide treatment or endogenous ceramide accumulation induces autophagy. When exposed to exogenous ceramides, an increase in the level of the autophagy-specific ubiquitin-like protein, ATG8e, associated with mitochondria, where it directly bound to ceramides. Taken together, we propose that the accumulation of ceramides in mitochondria can induce cell death by regulating autophagy.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Ceramidas/metabolismo , Ceramidas/farmacologia , Arabidopsis/metabolismo , Mitocôndrias/metabolismo , Autofagia , Morte Celular , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo
2.
Beijing Da Xue Xue Bao Yi Xue Ban ; 55(5): 886-892, 2023 Oct 18.
Artigo em Zh | MEDLINE | ID: mdl-37807744

RESUMO

OBJECTIVE: To investigate the association of isolated thyroid peroxidase antibody (TPOAb) positive in the first trimester with fetal growth. METHODS: A total of 16 446 pregnant women were included in the birth cohort study, whose last menstrual period was between May 2016 and April 2019 and with singleton pregnancy. Maternal serum samples were collected when they firstly came for prenatal care in the first trimester. The pregnant women were consecutively seen and followed in the hospital and the information of pregnant women was extracted from the electronic medical information system. The pregnant women were divided into isolated TPOAb positive group (n=1 654) and euthyroid group (n=14 792). Three fetal ultrasound examinations were scheduled during the routine prenatal visits at the hospital and were performed by trained sonographers. All fetal growth indicators were quantified as gestational age- and gender- adjusted standard deviation score (Z-score) using the generalized additive models for location, scale and shape (GAMLSS). Fetal growth indicators included estimated fetal weight (EFW), abdominal circumference (AC), biparietal diameter (BPD), femur length (FL) and head circumference (HC). Fetal growth restriction (FGR) was defined as AC or EFW Z-score<3rd centile based on clinical consensus. Generalized estimating equation (GEE) analysis was applied to assess the association of maternal isolated TPOAb positive with fetal growth. The generalized linear model was further used to analyze the association between isolated TPOAb positive and fetal growth indicator at different gestational ages when the fetal growth indicator was significantly associated with isolated TPOAb positive in the GEE mo-del. RESULTS: The median gestational age at three ultrasound measurements was 23.6 (23.3, 24.1), 30.3 (29.7, 30.9), 37.3 (37.0, 37.7) weeks, respectively. The BPD Z-score was higher in isolated TPOAb positive women, compared with the euthyroid pregnant women after adjustment (ß=0.057, 95%CI: 0.014-0.100, P=0.009). The generalized linear model showed the BPD Z-score was higher in the isolated TPOAb positive women at the end of 21-25 weeks (ß=0.052, 95%CI: 0.001-0.103, P=0.044), 29-32 weeks (ß=0.055, 95%CI: 0.004-0.107, P=0.035) and 36-40 weeks (ß=0.068, 95%CI: 0.011-0.125, P=0.020), compared with the euthyroid pregnant women. There was no difference in other fetal growth indicators (EFW, AC, FL and HC) and FGR between the isolated TPOAb positive and euthyroid pregnant women. CONCLUSION: The BPD Z-score was slightly increased in the isolated TPOAb positive pregnant women in the first trimester, while other fetal growth indicators were not changed. The reproducibility and practical significance of this result need to be confirmed.


Assuntos
Desenvolvimento Fetal , Iodeto Peroxidase , Gravidez , Feminino , Humanos , Primeiro Trimestre da Gravidez , Estudos de Coortes , Reprodutibilidade dos Testes , Peso Fetal , Retardo do Crescimento Fetal , Ultrassonografia Pré-Natal
3.
Plant J ; 107(5): 1447-1465, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34180563

RESUMO

Sphingolipids have key functions in plant membrane structure and signaling. Perturbations of plant sphingolipid metabolism often induce cell death and salicylic acid (SA) accumulation; SA accumulation, in turn, promotes sphingolipid metabolism and further cell death. However, the underlying molecular mechanisms remain unclear. Here, we show that the Arabidopsis thaliana lipase-like protein ENHANCED DISEASE SUSCEPTIBILITY 1 (EDS1) and its partner PHYTOALEXIN DEFICIENT 4 (PAD4) participate in sphingolipid metabolism and associated cell death. The accelerated cell death 5 (acd5) mutants accumulate ceramides due to a defect in ceramide kinase and show spontaneous cell death. Loss of function of EDS1, PAD4 or SALICYLIC ACID INDUCTION DEFICIENT 2 (SID2) in the acd5 background suppressed the acd5 cell death phenotype and prevented ceramide accumulation. Treatment with the SA analogue benzothiadiazole partially restored sphingolipid accumulation in the acd5 pad4 and acd5 eds1 double mutants, showing that the inhibitory effect of the pad4-1 and eds1-2 mutations on acd5-conferred sphingolipid accumulation partly depends on SA. Moreover, the pad4-1 and eds1-2 mutations substantially rescued the susceptibility of the acd5 mutant to Botrytis cinerea. Consistent with this, B. cinerea-induced ceramide accumulation requires PAD4 or EDS1. Finally, examination of plants overexpressing the ceramide synthase gene LAG1 HOMOLOGUE2 suggested that EDS1, PAD4 and SA are involved in long-chain ceramide metabolism and ceramide-associated cell death. Collectively, our observations reveal that EDS1 and PAD4 mediate ceramide (especially long-chain ceramide) metabolism and associated cell death, by SA-dependent and SA-independent pathways.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/genética , Hidrolases de Éster Carboxílico/metabolismo , Ceramidas/metabolismo , Proteínas de Ligação a DNA/metabolismo , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Doenças das Plantas/imunologia , Apoptose , Arabidopsis/imunologia , Arabidopsis/fisiologia , Proteínas de Arabidopsis/genética , Botrytis/fisiologia , Hidrolases de Éster Carboxílico/genética , Proteínas de Ligação a DNA/genética , Suscetibilidade a Doenças , Perfilação da Expressão Gênica , Transferases Intramoleculares/genética , Transferases Intramoleculares/metabolismo , Mutação com Perda de Função , Mutação , Fenótipo , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Doenças das Plantas/microbiologia , Ácido Salicílico/metabolismo , Sesquiterpenos/metabolismo , Esfingolipídeos/metabolismo , Fitoalexinas
4.
Plant Physiol ; 187(3): 1713-1727, 2021 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-34618068

RESUMO

Sphingolipids are structural components of the lipid bilayer that acts as signaling molecules in many cellular processes, including cell death. Ceramides, key intermediates in sphingolipid metabolism, are phosphorylated by the ceramide kinase ACCELERATED CELL DEATH5 (ACD5). The loss of ACD5 function leads to ceramide accumulation and spontaneous cell death. Here, we report that the jasmonate (JA) pathway is activated in the Arabidopsis (Arabidopsis thaliana) acd5 mutant and that methyl JA treatment accelerates ceramide accumulation and cell death in acd5. Moreover, the double mutants of acd5 with jasmonate resistant1-1 and coronatine insensitive1-2 exhibited delayed cell death, suggesting that the JA pathway is involved in acd5-mediated cell death. Quantitative sphingolipid profiling of plants treated with methyl JA indicated that JAs influence sphingolipid metabolism by increasing the levels of ceramides and hydroxyceramides, but this pathway is dramatically attenuated by mutations affecting JA pathway proteins. Furthermore, we showed that JAs regulate the expression of genes encoding enzymes in ceramide metabolism. Together, our findings show that JAs accelerate cell death in acd5 mutants, possibly by modulating sphingolipid metabolism and increasing ceramide levels.


Assuntos
Proteínas de Arabidopsis/genética , Arabidopsis/metabolismo , Morte Celular , Ciclopentanos/farmacologia , Oxilipinas/farmacologia , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Reguladores de Crescimento de Plantas/farmacologia , Esfingolipídeos/metabolismo , Proteínas de Arabidopsis/metabolismo , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo
5.
J Exp Bot ; 73(14): 4954-4967, 2022 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-35436324

RESUMO

Plant sphingolipids are important membrane components and bioactive molecules in development and defense responses. However, the function of sphingolipids in plant defense, especially against herbivores, is not fully understood. Here, we report that Spodoptera exigua feeding affects sphingolipid metabolism in Arabidopsis, resulting in increased levels of sphingoid long-chain bases, ceramides, and hydroxyceramides. Insect-induced ceramide and hydroxyceramide accumulation is dependent on the jasmonate signaling pathway. Loss of the Arabidopsis alkaline ceramidase ACER increases ceramides and decreases long-chain base levels in plants; in this work, we found that loss of ACER enhances plant resistance to S. exigua and improves response to mechanical wounding. Moreover, acer-1 mutants exhibited more severe root-growth inhibition and higher anthocyanin accumulation than wild-type plants in response to methyl jasmonate treatment, indicating that loss of ACER increases sensitivity to jasmonate and that ACER functions in jasmonate-mediated root growth and secondary metabolism. Transcript levels of ACER were also negatively regulated by jasmonates, and this process involves the transcription factor MYC2. Thus, our findings reveal that ACER is involved in mediating jasmonate-related plant growth and defense and that jasmonates function in regulating the expression of ACER.


Assuntos
Acer , Proteínas de Arabidopsis , Arabidopsis , Ceramidase Alcalina/genética , Ceramidase Alcalina/metabolismo , Animais , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Ceramidas/metabolismo , Ciclopentanos/metabolismo , Regulação da Expressão Gênica de Plantas , Herbivoria , Insetos , Oxilipinas/metabolismo , Esfingolipídeos/metabolismo
6.
Zhongguo Zhong Yao Za Zhi ; 47(12): 3339-3347, 2022 Jun.
Artigo em Zh | MEDLINE | ID: mdl-35851128

RESUMO

This study aimed to explore the potential mechanism of Zicui Decoction in the treatment of diabetic kidney disease(DKD) based on network pharmacology and molecular docking. The DKD-related targets were searched from DrugBank, Therapeutic Target Database(TTD), Online Mendelian Inheritance in Man Database(OMIM), GeneCards, DisGeNET, Comparative Toxico-genomics Database(CTD), and PharmGKB. The targets of the serum active ingredients of Zicui Decoction were predicted from the SwissTargetPrediction. The obtained results were then mapped to harvest the potential targets of Zicui Decoction against DKD. Cytoscape 3.8.2 was employed to construct the "serum active ingredient of Zicui Decoction-potential target-DKD" network. The protein-protein interaction(PPI) network was constructed using the STRING. The key targets were then subjected to Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis using the DAVID V6.8 for uncovering its action mechanims. The serum active ingredients of Zicui Decoction were then docked to the core terget proteins with PyMOL and AutoDock Vina. The results of network analysis showed that there were 173 targets associated with 12 serum active ingredients and 6 756 targets related to DKD. The mapping revealed 124 potential targets, of which 26 were the key targets of Zicui Decoction against DKD and 3 were the core teargets. GO analysis yielded 34 entries(P≤0.01 and benjamini≤0.01), and in the treatment of DKD with Zicui Decoction, such biological processes as ERK cascade, regulation of apoptosis, proliferation and migration, and regulation of fibroblast proliferation and ligand receptor binding were involved. According to the KEGG analysis, 19 signaling pathways(P≤0.01 and benjamini≤0.01) were screened out, among which the PI3 K-Akt signaling pathway, MAPK signaling pathway, Ras signaling pathway, and VEGF signaling pathway were closely associated with DKD. Molecular docking verified a good binding ability of the three serum active ingredients to the core targets. In conclusion, Zicui Decoction alleviates DKD possibly by inhibiting inflammation, regulating autophagy, and anti-fibrosis.


Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , Medicamentos de Ervas Chinesas , Diabetes Mellitus/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Medicina Tradicional Chinesa , Simulação de Acoplamento Molecular , Farmacologia em Rede
7.
Zhongguo Zhong Yao Za Zhi ; 47(19): 5383-5388, 2022 Oct.
Artigo em Zh | MEDLINE | ID: mdl-36472046

RESUMO

Tibetan medicine is an essential part of Chinese medicine and has unique theoretical experience and therapeutic advantages. According to the development principle of inheriting the essence, sticking to the truth, and keeping innovative, the supervision department should give clear and reasonable guidance considering the characteristics of Tibetan medicine, establish a standard system for quality control, clinical verification and evaluation, and accelerate the research and commercialization of new drugs. In view of the needs of drug supply-side reform and the current situation of Tibetan medicine and new pharmaceutical research, we ponder and provide suggestions on the confusion faced by the current supervision of Tibetan drug registration, hoping to contribute to the supervision strategy of Tibetan drug registration and the high-quality development of Tibetan medicine industry.


Assuntos
Medicina Tradicional Tibetana , Pesquisa Farmacêutica , Tibet , Controle de Qualidade , Indústria Farmacêutica
8.
Adv Exp Med Biol ; 1209: 23-41, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31728863

RESUMO

The highly conserved catabolic process of autophagy delivers unwanted proteins or damaged organelles to vacuoles for degradation and recycling. This is essential for the regulation of cellular homeostasis, stress adaptation, and programmed cell death in eukaryotes. In particular, emerging evidence indicates that autophagy plays a multifunctional regulatory role in plant innate immunity during plant-pathogen interactions. In this review, we highlight existing knowledge regarding the involvement of autophagy in plant immunity, mechanisms functioning in the induction of autophagy upon pathogen infection, and possible directions for future research.


Assuntos
Autofagia , Imunidade Vegetal , Homeostase , Imunidade Vegetal/imunologia , Vacúolos
9.
Chem Biodivers ; 16(1): e1800424, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30387325

RESUMO

Continually phytochemical study of the roots of Heracleum dissectum had led to the isolation of three previously undescribed polyacetylene glycosides (1-3), together with seven known compounds, including one polyacetylene (8) and six coumarins (4-7 and 9-10) using diverse chromatographic methods. The structures of these three new compounds were characterized and identified as deca-4,6-diyn-1-yl ß-d-glucopyranosyl-(1→6)-ß-d-glucopyranosyl-(1→2)-ß-d-glucopyranoside (1), (8Z)-dec-8-ene-4,6-diyn-1-yl ß-d-glucopyranosyl-(1→6)-ß-d-glucopyranosyl-(1→2)-ß-d-glucopyranoside (2), and (8E)-dec-8-ene-4,6-diyn-1-yl ß-d-glucopyranosyl-(1→6)-ß-d-glucopyranosyl-(1→2)-ß-d-glucopyranoside (3) based on their physicochemical properties and extensive analyses of various spectroscopic data. Their triglycerides accumulating activities were assayed and the results showed that the three new polyacetylene glycosides (1-3) exhibited triglyceride accumulating activities in 3T3-L1 adipocytes.


Assuntos
Glicosídeos/isolamento & purificação , Glicosídeos/farmacologia , Heracleum/química , Extratos Vegetais/farmacologia , Raízes de Plantas/química , Polímero Poliacetilênico/química , Triglicerídeos/metabolismo , Células 3T3-L1 , Animais , Configuração de Carboidratos , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Glicosídeos/química , Metanol/química , Camundongos , Extratos Vegetais/química , Espectroscopia de Prótons por Ressonância Magnética , Espectrometria de Massas por Ionização por Electrospray
10.
Zhongguo Zhong Yao Za Zhi ; 42(1): 6-9, 2017 Jan.
Artigo em Zh | MEDLINE | ID: mdl-28945018

RESUMO

Along with the increase of clinical application, the safety of traditional Chinese medicine gained more and more attentions. In particular, the safety evaluation of Chinese medical injections has become a mandatory task should be completed by pharmaceutical companies under the supervision of China Food and Drug Administration(CFDA). Due to the weak foundation of previous studies, the safety issues of Chinese medical injections have not been fully understood, and lack of scientific and rational risk management programs. Clinical safety centralized monitoring(CSCM) is an important method for post-market safety evaluation of Chinese medicine. Due to the lack of appropriate norms and procedures, the quality of similar research is uneven, and the results vary. Combined with practical experience with experts' suggestions, we developed this expert consensus on the design and implementation of CSCM from three stages (design, implementation and report) with 20 technical points, which will provide technical support for future CSCM studies.


Assuntos
Medicina Tradicional Chinesa/normas , Vigilância de Produtos Comercializados , China , Consenso , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Medicamentos de Ervas Chinesas/efeitos adversos , Medicamentos de Ervas Chinesas/normas , Humanos , Injeções , Controle de Qualidade
11.
Guang Pu Xue Yu Guang Pu Fen Xi ; 35(6): 1520-4, 2015 Jun.
Artigo em Zh | MEDLINE | ID: mdl-26601359

RESUMO

High density polyethylene (HDPE) was widely used as rotational packaging case in the material reserve field. The chemical changes of HDPE, exposed to particular climatic conditions of tropic marine atmosphere for one year-long in Wanning Hainan, were elucidated by the attenuated total reflection infrared spectroscopy (ATR-FTIR). The structural changes were studied qualitatively, mainly from the polymeric chain breaking, branching and oxidation to distinguish the degradation profile. The variations of crystallinity & carbonyl index were also studied quantitatively according to the characteristic peaks intensity & area ratio. Finally, the relationships between structural changes and mechanical properties were investigated. The results showed that the polymeric chain breaking & branching play a leading role before 3 months in the aging progress. Then oxidation phenomena gradually takes place during 3-6 months. The chain branching & oxidation were predominant factors after 6 months. Nine months later, the oxidation was saturated gradually. Furthermore, the aging process is positively correlated to the temperature and irradiation. After 12 months aging, the carbonyl index increased by 112 times and crystallinity was 10% higher than before. The tensile/bending modulus deceased faster than tensile/bending strength of HDPE. The linear degree of tensile modulus and carbonyl index was 0.97. The degree of linearity of tensile strength and crystallinity calculated by feature bands (720-730 cm(-1)) was 0.96. It showed that the mechanical properties of HDPE can be speculated from the structural changes by ATR-FTIR.

12.
Exp Ther Med ; 27(6): 268, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38756904

RESUMO

The anesthetic drug, ketamine (KTM) has been shown to induce therapeutic effects against major depressive disorder (MDD), however the related underlying mechanisms remain unclear. In the present study, HT22 neuronal cells were treated with glutamate to imitate oxidative stress injury in MDD, and it was hypothesized that the cannabinoid type 1 (CB1) receptor mediates KTM-induced neuroprotection via ameliorating mitochondrial function in glutamate-treated neuronal cells. Compared with the control, glutamate decreased cell viability and intracellular antioxidants, including glutathione (GSH), catalase and superoxide dismutase 2 levels, and inhibited mitochondrial function simultaneously. Moreover, glutamate increased lactate dehydrogenase release, cellular apoptosis level, cleaved caspase-3 expression and intracellular oxidants, such as reactive oxygen species, oxidized GSH and mitochondrial superoxide in the cells. The presence of KTM, however, significantly decreased the glutamate-induced oxidative stress injury, ameliorated the antioxidant/oxidant levels in the cells, enhanced mitochondrial function and upregulated CB1 receptor expression (P<0.05). Co-administration of the CB1 receptor antagonist AM251 markedly abolished the KTM-induced cytoprotective effects and ameliorations of antioxidant/oxidant levels and mitochondrial function, and also reversed CB1 upregulation (P<0.05). These observations indicated that KTM decreases the oxidative stress injury caused by glutamate in HT22 neuronal cells, and the neuroprotective effects may be mediated by the CB1 receptor.

13.
J Womens Health (Larchmt) ; 32(11): 1174-1181, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37638829

RESUMO

Background: Differentiated thyroid cancer (DTC) is increasingly common in women of reproductive age. However, whether pregnancy increases the risk of DTC progression/recurrence after treatment remains controversial. The study aimed to assess the association of pregnancy with risk of progression in patients previously treated for DTC. Methods: This was a retrospective cohort study following 123 pregnant women and 1376 nonpregnant women at Peking University Third Hospital after initial treatment for DTC between January 2012 and December 2022. To control the effect of confounding, we carefully matched pregnancy (n = 107) and nonpregnancy groups (n = 298) in terms of baseline characteristics by using propensity score matching (PSM). Results: At baseline, the pregnancy and nonpregnancy groups were balanced in all matched variables. At follow-up, the percentage of DTC progression in the two groups was 12 (11.8%) and 47 (15.8%), respectively. Regression models showed no evidence of association of pregnancy with the risk of progression (odds ratio: 0.74 and 95% confidence interval: 0.37-1.50; p = 0.404), and remained consistent across long/short follow-up and other subgroup variables. We found that the shorter the time interval between treatment and pregnancy, the higher the risk of DTC progression (ptrend = 0.019). Conclusions: The risk of DTC progression in pregnant women was not higher than that in the well-matched, nonpregnant women. For young women previously treated for DTC, disease progression might not be a concern for their future pregnancy plan, but it seems safer to wait at least 1 year before pregnancy compared with immediate pregnancy.


Assuntos
Neoplasias da Glândula Tireoide , Humanos , Feminino , Gravidez , Estudos Retrospectivos , Pontuação de Propensão , Neoplasias da Glândula Tireoide/epidemiologia , Progressão da Doença
14.
Neural Regen Res ; 18(3): 618-625, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36018186

RESUMO

Studies on ischemia/reperfusion (I/R) injury suggest that exogenous neural stem cells (NSCs) are ideal candidates for stem cell therapy reperfusion injury. However, NSCs are difficult to obtain owing to ethical limitations. In addition, the survival, differentiation, and proliferation rates of transplanted exogenous NSCs are low, which limit their clinical application. Our previous study showed that neuregulin1ß (NRG1ß) alleviated cerebral I/R injury in rats. In this study, we aimed to induce human umbilical cord mesenchymal stem cells into NSCs and investigate the improvement effect and mechanism of NSCs pretreated with 10 nM NRG1ß on PC12 cells injured by oxygen-glucose deprivation/reoxygenation (OGD/R). Our results found that 5 and 10 nM NRG1ß promoted the generation and proliferation of NSCs. Co-culture of NSCs and PC12 cells under condition of OGD/R showed that pretreatment of NSCs with NRG1ß improved the level of reactive oxygen species, malondialdehyde, glutathione, superoxide dismutase, nicotinamide adenine dinucleotide phosphate, and nuclear factor erythroid 2-related factor 2 (Nrf2) and mitochondrial damage in injured PC12 cells; these indexes are related to ferroptosis. Research has reported that p53 and solute carrier family 7 member 11 (SLC7A11) play vital roles in ferroptosis caused by cerebral I/R injury. Our data show that the expression of p53 was increased and the level of glutathione peroxidase 4 (GPX4) was decreased after RNA interference-mediated knockdown of SLC7A11 in PC12 cells, but this change was alleviated after co-culturing NSCs with damaged PC12 cells. These findings suggest that NSCs pretreated with NRG1ß exhibited neuroprotective effects on PC12 cells subjected to OGD/R through influencing the level of ferroptosis regulated by p53/SLC7A11/GPX4 pathway.

15.
Pain Ther ; 12(3): 707-722, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36928500

RESUMO

INTRODUCTION: This study was conducted to observe the effect of transcutaneous electrical acupoint stimulation (TEAS) on the postoperative sleep quality of patients undergoing gastrointestinal tumor surgery and to verify the possible mechanism. METHODS: Eighty-three patients were allocated to the TEAS or Sham group. Patients in the TEAS group received TEAS treatment (disperse-dense waves; frequency, 2/100 Hz) on bilateral Shenmen (HT7), Neiguan (PC6) and Zusanli (ST36) points for 30 min each time, total three times in the perioperative period. In the Sham group, electrodes were placed; however, no current was given. Sleep quality was assessed on the day before surgery (P1) and the first and third days after surgery (D1 and D3) using the Pittsburgh Sleep Quality Index (PSQI) and Athens Insomnia Scale (AIS). Postoperative pain was assessed using visual analog scale (VAS) 72 h postoperatively. The incidences of abdominal distension, dizziness, postoperative nausea and vomiting (PONV) and pulmonary complications were recorded. Serum levels of inflammatory cytokines and the expression of key factors of oxidative stress and key molecules of the nuclear factor erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE) signal pathway were measured. RESULTS: TEAS ameliorated sleep quality at D1 and D3 (PSQI P < 0.05, AIS P < 0.05) and decreased postoperative pain as demonstrated by lower VAS scores compared to the Sham group (P < 0.05). The incidences of abdominal distension and PONV were also lower in the TEAS group. Markers of oxidative stress were increased (P < 0.05), and the serum concentration of interleukin-6 (IL-6) was significantly lower in the TEAS group. The key mediators of the Nrf2/ARE pathway were enhanced after TEAS. CONCLUSION: Perioperative TEAS improved postoperative sleep quality, reduced postoperative pain and alleviated postoperative adverse effects in patients undergoing laparoscopic gastrointestinal tumor surgery resection. This may be associated with activating Nrf2/ARE signal pathway and decreasing its inflammatory actions. TRIAL REGISTRATION: Chinese Clinical Trial Registry ( http://www.chictr.org.cn/index.aspx ), ChiCTR2100054971.

16.
Cancer Sci ; 103(1): 73-9, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22017425

RESUMO

Several studies have found that the promoter CpG island is frequently methylated in gastric cancer. The CpG island methylator phenotype (CIMP) defines concordant methylation of multiple promoter CpG island loci in a subset of gastric cancer. However, the relationship between CIMP and lymph node metastasis in gastric cancer is unknown. Our study aimed to characterize the role of CIMP in lymph node metastasis. Clinical specimens from 120 patients were analyzed and PCR was used to detect the methylation status of five genes (ALX4, TMEFF2, CHCHD10, IGFBP3, and NPR1). We measured the level of mRNA for the five genes by real-time RT-PCR. Microsatellite instability and Helicobacter pylori infection status were assayed by capillary electrophoresis and real-time PCR, respectively. DNA methylation in the five genes was correlated with low expression of the respective mRNA. With CIMP as the dependent variable, CIMP-high gastric cancer tended to show more distant lymph node metastasis, higher pathologic tumor classification, more pathologic metastasis, and higher pathologic TNM status. Microsatellite instability and H. pylori status were not significant predictors of prognosis. CIMP-high gastric cancer showed significantly worse survival compared with that of CIMP-low/CIMP-negative gastric cancer (P < 0.001). Our results show that there is an association between CIMP status and lymph node metastasis in gastric cancer and CIMP-high was an independent prognostic factor.


Assuntos
Ilhas de CpG/genética , Metilação de DNA , Regulação Neoplásica da Expressão Gênica , Genes Supressores de Tumor , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteínas de Ligação a DNA/genética , Feminino , Infecções por Helicobacter/genética , Infecções por Helicobacter/patologia , Infecções por Helicobacter/virologia , Helicobacter pylori/genética , Humanos , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Metástase Linfática , Masculino , Proteínas de Membrana/genética , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Proteínas Mitocondriais/genética , Proteínas de Neoplasias/genética , Estadiamento de Neoplasias , Fenótipo , Prognóstico , RNA Neoplásico , Reação em Cadeia da Polimerase em Tempo Real , Receptores do Fator Natriurético Atrial/genética , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/virologia , Taxa de Sobrevida , Fatores de Transcrição/genética
17.
Zhonghua Yu Fang Yi Xue Za Zhi ; 46(8): 692-6, 2012 Aug.
Artigo em Zh | MEDLINE | ID: mdl-23157861

RESUMO

OBJECTIVE: To analyze the status of dietary intake of Chinese adults in 2010. METHODS: In 2010, China Chronic Disease Surveillance was carried out in 31 provinces and Xinjiang Production and Construction Corps. The survey was undertaken in 162 surveillance sites in the national disease surveillance points system by stratified multi-stage cluster random sampling. The participants were local residents (living in the area for more than 6 months) aged 18 years and above in the surveillance sites. A semi-quantitative food frequency questionnaire was used to measure the dietary intake for 97 187 urban and rural adults aged 18 years and above. After complex weighting for the sample, the average daily consumption for major food was analyzed for different genders and regions. RESULTS: After complex weighting, the median of cereal, rice and wheat flour intake for Chinese adults was 375.0 g. The median of livestock meat intake was 57.1 g with western areas (85.7 g) much higher than eastern (57.1 g) and central areas (46.2 g) (χ² = 2054.82, P < 0.01). The median of poultry intake was 7.1 g, eastern areas (10.0 g) higher than western and central areas (both 6.7 g) (χ² = 1210.86, P < 0.01). The median of seafood intake was 14.3 g, eastern (15.0 g) much higher than central (14.3 g) and western areas (7.1 g) (χ² = 5603.37, P < 0.01). The median of daily intake for eggs was 21.4 g, western (14.3 g) lower than eastern and central areas (both 21.4 g) (χ² = 1699.11, P < 0.01). The median of dairy product intake was 42.9 g, eastern (57.1 g) higher than western and central areas (both 35.7 g) (χ² = 196.35, P < 0.01). Overall, 52.8% of urban and rural residents did not meet recommended amount of fruit and vegetable intake. The rate of inadequate intake of fruit and vegetable was higher in rural (55.7%) than urban areas (46.1%, χ² = 929.43, P < 0.01). CONCLUSION: The adult intake of cereal category foods tended to decline in 2010, and the intakes of vegetable and fruits, fishery products as well as dairy products were evidently deficient and regionally varied.


Assuntos
Comportamento Alimentar , Inquéritos Nutricionais , Adolescente , Adulto , China , Laticínios , Grão Comestível , Feminino , Frutas , Humanos , Masculino , Carne , Pessoa de Meia-Idade , Verduras , Adulto Jovem
18.
Zhong Yao Cai ; 35(11): 1795-8, 2012 Nov.
Artigo em Zh | MEDLINE | ID: mdl-23627092

RESUMO

OBJECTIVE: To study the chemical constituents from root bark of Discocleidion rufescens. METHODS: Column chromatography and spectral analysis were used to isolate and identify the constituents. RESULTS: Ten compounds were obtained and identified from root bark of Discocleidion rufescens including beta-sitosterol (I), scopoletin (II), daucosterol (III), ricinine (IV), chrysophanol (V), aphyscion (VI), taraxerol (VII), pigenin (VIII), luteolin (IX), gallic acid (X). CONCLUSION: Ten compounds are isolated for the first time from root bark of Discocleidion rufescens. The monomer of Compounds II is isolated from this genus for the first time.


Assuntos
Antraquinonas/análise , Euphorbiaceae/química , Raízes de Plantas/química , Escopoletina/análise , Sitosteroides/análise , Alcaloides/análise , Alcaloides/química , Antraquinonas/química , Ácido Gálico/análise , Ácido Gálico/química , Luteolina/análise , Luteolina/química , Estrutura Molecular , Ácido Oleanólico/análogos & derivados , Ácido Oleanólico/análise , Ácido Oleanólico/química , Casca de Planta/química , Piridonas/análise , Piridonas/química , Escopoletina/química , Sitosteroides/química , Espectrofotometria Infravermelho
19.
Biomed Pharmacother ; 153: 113468, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36076494

RESUMO

Calanthe fimbriata Franch. is a Tujia ethnic herb, which has traditionally been used to treat gastric ulcers, chronic hepatitis, etc. We explored the chemical constitutes, gastroprotective effects, and the active fraction of C. fimbriata, as well as elucidating the underlying mechanisms. Firstly, four in vitro antioxidant tests were applied to determine the oxidation resistance of C. fimbriata methanol extract and its fractions. The gastroprotective effects were evaluated in ethanol-induced gastric ulcer rats, gastric histopathology was visualized by H&E staining, and the acidity of gastric juice was measured by titrating with NaOH solution. The contents of malondialdehyde, catalase, superoxide dismutase, gastrin, and the activity of H+K+-ATPase were estimated using commercial kits. EtOAc fraction of C. fimbriata methanol extract (CfEF) exhibited significant gastroprotective effects by ameliorating stomach pathological changes and elevating the pH value of gastric juice. It also manifested remarkable antioxidant activities in vitro and in vivo. Using various chromatographic methods and spectroscopic techniques, 22 compounds were isolated and characterized from CfEF, in which alkaloids were the predominant components. All of these substances were derived from C. fimbriata for the first time. The results indicated that CfEF is a promising source of gastroprotective agents. The antioxidant activity of this herb, as well as prevention of gastrin secretion and inhibition of H+K+ -ATPase, was found to be the underlying mechanism of action.


Assuntos
Antiulcerosos , Orchidaceae , Úlcera Gástrica , Animais , Antiulcerosos/uso terapêutico , Antioxidantes/uso terapêutico , Mucosa Gástrica , Gastrinas/metabolismo , ATPase Trocadora de Hidrogênio-Potássio/metabolismo , Metanol/química , Extratos Vegetais/uso terapêutico , Ratos , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/prevenção & controle
20.
Front Plant Sci ; 13: 824585, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35463421

RESUMO

Ceramide synthases (CSs) produce ceramides from long-chain bases (LCBs). However, how CSs regulate immunity and cell death in Arabidopsis thaliana remains unclear. Here, we decipher the roles of two classes of CS, CSI (LAG1 HOMOLOG 2, LOH2) and CSII (LOH1/3), in these processes. The loh1-2 and loh1-1 loh3-1 mutants were resistant to the bacterial pathogen Pseudomonas syringae pv maculicola (Psm) DG3 and exhibited programmed cell death (PCD), along with increased LCBs and ceramides, at later stages. In loh1-2, the Psm resistance, PCD, and sphingolipid accumulation were mostly suppressed by inactivation of the lipase-like proteins ENHANCED DISEASE SUSCEPTIBILITY 1 (EDS1) and PHYTOALEXIN DEFICIENT 4 (PAD4), and partly suppressed by loss of SALICYLIC ACID INDUCTION DEFICIENT 2 (SID2). The LOH1 inhibitor fumonisin B1 (FB1) triggered EDS1/PAD4-independent LCB accumulation, and EDS1/PAD4-dependent cell death, resistance to Psm, and C16 Cer accumulation. Loss of LOH2 enhances FB1-, and sphinganine-induced PCD, indicating that CSI negatively regulates the signaling triggered by CSII inhibition. Like Cer, LCBs mediate cell death and immunity signaling, partly through the EDS1/PAD4 pathway. Our results show that the two classes of ceramide synthases differentially regulate EDS1/PAD4-dependent PCD and immunity via subtle control of LCBs and Cers in Arabidopsis.

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