Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 77
Filtrar
1.
Phys Rev E ; 103(2-1): 023213, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33735973

RESUMO

The formation and structure of a collisional shock wave in a fully ionized plasma is studied via full particle-in-cell simulations, which allows the complex momentum and energy transfer processes between different charged particles to be treated self-consistently. The kinetic energy of the plasma flow drifting towards a reflecting piston is found to be rapidly converted into thermal motion under the cooperative effects of ion-ion collisions, ion-electron collisions, and electric field charged-particle interactions. The subsequent shock evolution is influenced by the "precursor" ion beam before a quasisteady state is reached. The shock wave structure is then analyzed from a two-fluid transport viewpoint, which is found to be affected by "flux-limiting" electron transport, the nonthermal ions, and the charge separation electric field.

2.
Zhongguo Zhong Yao Za Zhi ; 46(2): 412-419, 2021 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-33645130

RESUMO

In this paper, Asarum polysaccharides(AP) were extracted, and its composition was analyzed to study the activity against H1 N1 influenza virus in vitro and its intervention effect on mice with kidney Yang deficiency syndrome. AP was prepared by the strategy of water extraction and alcohol precipitation, the content was determined, and its monosaccharide composition was analyzed. The cell Real-time monitoring system and Reed-Muench model were adopted to evaluate the antiviral activity of AP in vitro. And the mouse model of kidney Yang deficiency syndrome was established in vivo to compare the efficacy of Mahuang Xixin Fuzi Decoction(MXF) and AP. MXF group and AP group were treated with clinical equivalent doses of 1.8 g·kg~(-1)·d~(-1) and 0.077 g·kg~(-1)·d~(-1) respectively, once a day for 6 consecutive days. Real-time PCR was used to detect the relative expression of M gene of H1 N1 influenza virus and cytokines in lung tissue. The content of AP in Asarum was 25.22%, and the protein content was 0.8%. And the monosaccharide composition was identified as L-rhamnose, D-arabinose, D-xylose, D-glucose, D-galactose and D-mannose. TI values of Tamiflu, MXF and AP were 30.00, 8.06 and 10.33, respectively. Three different doses of AP could significantly reduce the concentration of virus in supernatant. Compared with the model mice, lung indexes of MXF group and AP group decreased significantly(P<0.05), and the relative expression of M gene decreased significantly(P<0.05). The relative expressions of IL-10 and IFN-γ were up-regulated to varying degrees, while the relative gene expressions of IL-1ß, IL-6 and MCP-1 were down-regulated to different degrees. In addition, AP could significantly enhance the expression of TNF-α(P<0.01). AP had a good anti-influenza virus activity in vitro, and could protect mice with kidney Yang deficiency syndrome by reducing the viral load in lung tissue, decreasing inflammation damage in lung tissue, and regulating the expression of inflammatory cytokines. Compared with the prescription of MXF, AP had a better antiviral activity.


Assuntos
Asarum , Medicamentos de Ervas Chinesas , Vírus da Influenza A Subtipo H1N1 , Influenza Humana , Animais , Antivirais/uso terapêutico , Citocinas/genética , Influenza Humana/tratamento farmacológico , Influenza Humana/genética , Pulmão , Camundongos , Polissacarídeos
3.
iScience ; 24(1): 101932, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33409478

RESUMO

Sexual selection can favor production of exaggerated features, but the high cost of such features in terms of energy consumption and enemy avoidance makes them go to extinction under the influence of natural selection. However, fossils preserved with specialized features are very rare. Here, we report a new nymph from Burmese amber, Magnusantena wuae Du & Chen gen. et sp. nov., which has exaggerated leaf-like expanded antennae. Such bizarre antennae indicate that sensitive and delicate sensory system and magnificent appearance in Hemiptera have been already established in mid-Cretaceous. Our findings may provide evidence for Darwin's view that sensory organs play an important role in sexual selection. This nymph with the leaf-like antennae may also represents a new camouflage pattern. However, the oversized antennae are costly to develop and maintain, increasing the risks from predators. Such unparalleled expanded antennae might be the key factor for the evolutionary fate of the coreid.

4.
Food Sci Nutr ; 8(8): 4472-4483, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32884727

RESUMO

The biogenic amines (BAs), water activity, pH, thiobarbituric acid-reactive substances (TBARS), and nitrite were, respectively, tested in dry fermented sausage with starter cultures (37x-6 Lactobacillus plantarum, x3-3b L. plantarum, 30x-11 Staphylococcus pentosans, and 37x-8 S. pentosans), during storage of room temperature (20°C) and refrigeration storage (4°C). Tryptamine (TRM), 2-phenylethylamine (PHE), putrescine (PUT), cadaverine (CAD), histamine (HIM), and tyramine (TYM) contents of all samples were increased storage at 20°C, and the content of TRM, PUT, CAD, and HIM of all samples storage at 20°C was higher than that storage at 4°C after 42 days. The content of BA with 37x-6, x3-3b, and 37x-8 was obviously decreased at 4°C storage. The storage temperature has a significant effect on BA content (p < .05) for TYM and other BAs tested. Finally, x3-3b, 37x-6, and 37x-8 should be used to produce fermented sausages on the basis of the concentration of BAs.

5.
Eur J Pharmacol ; 879: 173154, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32360836

RESUMO

Leonurus japonicus (motherwort) has been widely used to treat gynecological disorders, in which estrogen is often dysregulated, for a long time in China and other Asian countries. However, the chemical constituents and mechanisms underlying the activity of this medicinal plant are not fully understood. Seventeen of forty-six tested natural products from L. japonicus showed stimulatory or inhibitory effects on estrogen biosynthesis with different potency in human ovarian granulosa-like KGN cells. Luteolin-7-methylether (XLY29) potently inhibited 17ß-estradiol production (IC50: 5.213 µM) by decreasing the expression of aromatase, the only enzyme in vertebrates that catalyzes the biosynthesis of estrogens, but had no effect on the catalytic activity of aromatase. XLY29 decreased the expression of aromatase promoter I.3/II, and suppressed the phosphorylation of cAMP response element-binding protein. XLY29 potently inhibited phosphorylation of p38 mitogen-activated protein kinase and AKT but had no effect on phosphorylation of extracellular signal-regulated kinase and c-Jun N-terminal kinase. XLY29 also decreased the serum 17ß-estradiol level and disturbed estrous cycle in mice. These results suggest that modulation of estrogen biosynthesis is a novel effect of L. japonicus, and XLY29 warrants further investigation as a new therapeutic means for the treatment of estrogen-related diseases.


Assuntos
Produtos Biológicos/farmacologia , Estradiol/metabolismo , Estrogênios/metabolismo , Células da Granulosa/efeitos dos fármacos , Leonurus , Luteolina/farmacologia , Compostos Fitoquímicos/farmacologia , Animais , Aromatase/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Feminino , Células da Granulosa/metabolismo , Humanos , Camundongos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Ratos Sprague-Dawley
6.
Sci Rep ; 10(1): 2678, 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32042054

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

7.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 50(6): 872-877, 2019 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-31880120

RESUMO

OBJECTIVE: To study the relationship between the copy numbers of repetitive units at variable number tandem repeat (VNTR) loci of Mycobacterium tuberculosis complex (MTBC) with its diversity of protein profiles. METHODS: The MTBC strains were subjected to genotyping using multiple locus variable number tandem repeat analysis (MLVA). Also, the principal component analysis (PCA) was performed for bacterial protein profiles of MTBC using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The relationship between the polymorphism of VNTR loci and PCA clustering was analyzed. RESULTS: A total of 157 MTBC strains were collected. 146 MTBC strains (MS identification score values ≥1.700) were performed PCA and three clusters, clusterⅠ(61 strains), clusterⅡ(26 strains) and cluster Ⅲ(59 strains), were generated. Polymorphic diversities were observed in 24 VNTR loci, among them, 7 were highly various, 7 were moderately, and 10 were low various. The polymorphism of Mtub39, QUB26 and QUB4156 loci were correlated with the results of MALDI-TOF MS clustering (P=0.000, P=0.035, P=0.017). CONCLUSION: The polymorphism of Mtub39, QUB26 and QUB4156 loci in MTBC was correlated with the difference of MALDI-TOF MS protein profiles, suggesting that these loci may play a role in regulating the composition of protein profiles of MTBC strains.


Assuntos
Repetições Minissatélites , Mycobacterium tuberculosis , Genótipo , Polimorfismo Genético , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
8.
Sci Rep ; 9(1): 14782, 2019 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-31664070

RESUMO

The aquatic and semiaquatic invertebrates in fossiliferous amber have been reported, including taxa in a wide range of the subphylum Crustacea of Arthropoda. However, no caridean shrimp has been discovered so far in the world. The shrimp Palaemon aestuarius sp. nov. (Palaemonidae) preserved in amber from Chiapas, Mexico during Early Miocene (ca. 22.8 Ma) represents the first and the oldest amber caridean species. This finding suggests that the genus Palaemon has occupied Mexico at least since Early Miocene. In addition, the coexistence of the shrimp, a beetle larva, and a piece of residual leaf in the same amber supports the previous explanations for the Mexican amber depositional environment, in the tide-influenced mangrove estuary region.


Assuntos
Fósseis , Palaemonidae/fisiologia , Aclimatação , Âmbar/história , Animais , Besouros/anatomia & histologia , Ecossistema , Estuários , Fósseis/anatomia & histologia , Fósseis/história , História Antiga , México , Palaemonidae/anatomia & histologia , Paleontologia
9.
Biochem Pharmacol ; 162: 132-141, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30347204

RESUMO

Previous studies have shown that oxidative stress-induced inhibition of autophagy plays a pivotal role in cadmium (Cd)-mediated cytotoxicity in primary rat proximal tubular (rPT) cells. The objective of this study is to explore the protective effect of puerarin (PU), a potent antioxidant, on Cd-induced autophagy inhibition and oxidative stress in rPT cells. First, Cd-induced blockage of autophagic flux in rPT cells was obviously restored by PU treatment, evidenced by immunoblot analysis of autophagy marker proteins and tandem fluorescent-tagged LC3 method. Resultantly, Cd-induced autophagosome accumulation was significantly alleviated by PU treatment. Also, Cd-induced lysosomal alkalinization and impairment of lysosomal degradation capacity were obviously recovered by PU, demonstrating that PU can restore Cd-induced lysosomal dysfunction. Moreover, Cd-induced lysosomal membrane permeabilization (LMP) was effectively blocked by PU. Cd-stimulated Nrf2 nuclear translocation and subsequent elevated expression of Nrf2-downstream targets were significantly inhibited by PU treatment. Simultaneously, Cd-elevated protein levels of antioxidant enzymes and glutathione synthesis-related proteins in rPT cells were markedly downregulated by PU treatment. In conclusion, these observations indicate that PU alleviates Cd-induced cytotoxicity in rPT cells through restoring autophagy, blocking LMP and inhibiting Nrf2 pathway, which is intimately related with its antioxidant activity.


Assuntos
Cádmio/toxicidade , Isoflavonas/farmacologia , Túbulos Renais Proximais/efeitos dos fármacos , Lisossomos/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/antagonistas & inibidores , Vasodilatadores/farmacologia , Animais , Células Cultivadas , Relação Dose-Resposta a Droga , Túbulos Renais Proximais/metabolismo , Lisossomos/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia
10.
Biochim Biophys Acta Mol Cell Res ; 1866(4): 713-726, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30528975

RESUMO

Lead (Pb) is a known nephrotoxicant that causes damage to proximal tubular cells. PERK pathway plays an important role in the pathogenesis of renal diseases, but its role in Pb-induced nephrotoxicity remains largely unknown. In this study, data showed that Pb could induce ER stress as shown by increased phosphorylation of PERK with subsequent activation of the eIF2α-ATF4-CHOP axis in primary rat proximal tubular (rPT) cells, indicating the activation of PERK-eIF2α-ATF4-CHOP pathway due to excessive ER stress. Pb-activated PERK pathway can be effectively inhibited by 4-phenylbutyric acid and PERK gene silencing, respectively; whereas continuously up-regulated by tunicamycin (TM) treatment. Moreover, Pb-induced apoptosis and inhibition of autophagic flux in rPT cells were significantly augmented and aggravated by co-treatment with TM, respectively. Pharmacological or genetic inhibition of the PERK pathway results in alleviation of apoptosis and restoration of autophagy inhibition in Pb-exposed rPT cells. Mechanistically, activation of PERK-eIF2α-ATF4-CHOP axis triggered by excessive ER stress in rPT cells leads to Pb-induced apoptosis and blockage of autophagic flux, resulting in nephrotoxicity.


Assuntos
Estresse do Retículo Endoplasmático , Túbulos Renais Proximais/efeitos dos fármacos , Chumbo/toxicidade , eIF-2 Quinase/metabolismo , Fator 4 Ativador da Transcrição/metabolismo , Animais , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Células Cultivadas , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Fator de Iniciação 2 em Eucariotos/metabolismo , Túbulos Renais Proximais/enzimologia , Túbulos Renais Proximais/metabolismo , Fenilbutiratos/farmacologia , Ratos Sprague-Dawley , Fator de Transcrição CHOP/metabolismo , Tunicamicina/farmacologia , eIF-2 Quinase/genética
11.
Zhongguo Zhong Yao Za Zhi ; 43(21): 4288-4294, 2018 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-30583631

RESUMO

A new composite organic oscillating reaction system based on BrO3-Ce(SO4)2-H2SO4-malonic acid/tartaric acid was proposed in this paper. On the basis of the influence of the concentration of each component on the stability and characteristic parameters of the blank system, the electrochemical fingerprints of 30 kinds of traditional Chinese medicines (TCM) were obtained. The results showed that the electrochemical fingerprint can be used for the identification of TCMs, the distinguishment of different parts and the appraisal of genuineness, which is fast, sensitive and accurate. At the same time, we explored and verified the mechanism of oscillation and the formation mechanism of TCM fingerprint.


Assuntos
Medicamentos de Ervas Chinesas/química , Técnicas Eletroquímicas , Malonatos/química , Tartaratos/química , Medicina Tradicional Chinesa , Compostos Fitoquímicos/análise
12.
Org Lett ; 20(19): 6314-6317, 2018 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-30256123

RESUMO

Premnafulvol A (1), a unique diterpenoid featuring a 6/5/7/3-fused tetracyclic carbon skeleton, with three biosynthetically related analogues, premnafulvols B-D (2-4), were isolated from the aerial parts of Premna fulva. Structures of 1-4 were established by a combination of extensive spectroscopic analyses, quantum chemical calculations, and X-ray crystallography. Plausible biosynthetic pathways of 1-4 were proposed. Interestingly, 2 and 3 exhibited opposite effects on estrogen biosynthesis in human ovarian granulosa-like KGN cells by modulating the expression of aromatase.


Assuntos
Diterpenos/química , Lamiaceae/química , Aromatase/genética , Vias Biossintéticas , Linhagem Celular Tumoral , Diterpenos/isolamento & purificação , Feminino , Regulação da Expressão Gênica , Humanos , Modelos Moleculares , Estrutura Molecular , Componentes Aéreos da Planta/química , Estereoisomerismo , Relação Estrutura-Atividade
13.
J Inorg Biochem ; 182: 184-193, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29501979

RESUMO

Autophagy and apoptosis are two different biological processes that determine cell fates. We previously reported that autophagy inhibition and apoptosis induction are involved in lead(II)-induced cytotoxicity in primary rat proximal tubular (rPT) cells, but the interplay between them remains to be elucidated. Firstly, data showed that lead(II)-induced elevation of LC3-II protein levels can be significantly modulated by 3-methyladenine or rapamycin; moreover, protein levels of Autophagy-related protein 5 (Atg5) and Beclin-1 were markedly up-regulated by lead(II) treatment, demonstrating that lead(II) could promote the autophagosomes formation in rPT cells. Next, we applied three pharmacological agents and genetic method targeting the early stage of autophagy to validate that enhancement of autophagosomes formation can inhibit lead(II)-induced apoptotic cell death in rPT cells. Simultaneously, lead(II) inhibited the autophagic degradation of rPT cells, while the addition of autophagic degradation inhibitor bafilomycin A1 aggravated lead(II)-induced apoptotic death in rPT cells. Collectively, this study provided us a good model to know about the dynamic process of lead(II)-induced autophagy in rPT cells, and the interplay between autophagy and apoptosis highlights a new sight into the mechanism of lead(II)-induced nephrotoxicity.


Assuntos
Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Túbulos Renais Proximais/citologia , Chumbo/toxicidade , Adenina/análogos & derivados , Adenina/farmacologia , Animais , Proteína 5 Relacionada à Autofagia/metabolismo , Proteína Beclina-1/metabolismo , Células Cultivadas , Proteínas Associadas aos Microtúbulos/metabolismo , Ratos , Sirolimo/farmacologia
14.
Zhonghua Nan Ke Xue ; 24(11): 1021-1028, 2018 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-32212478

RESUMO

OBJECTIVE: To explore the effects of the Chinese herbal compound Tongjingling (TJL) on the ROS level, mitochondrial membrane potential (MMP) and mitochondrial ultrastructure in spermatogenic cells in varicocele (VC) rats with liver-qi stagnation (LQS). METHODS: Totally, 72 male SPF Wistar rats were randomly divided into six groups of equal number, sham operation, VC+LQS model, low-, medium- and high-dose TJL, and L-carnitine (LC) control. The VC+LQS model was established by the Saypol method combined with tail-clamping. At 4 weeks after modeling, the rats in the low-, medium- and high-dose TJL groups were treated intragastrically with TJL at 0.6, 1.2 and 2.4 g/ml respectively, those in the sham operation and VC+LQS model groups with 0.9% saline, and those in the LC control group with LC oral liquid at 2.1 ml/kg, qd, for 8 weeks. Then the ROS level and MMP in the spermatogenic cells were measured by flow cytometry and the mitochondrial ultrastructure observed under the transmission electron microscope. RESULTS: The ROS level in the spermatogenic cells was significantly higher in the VC+LQS model and low-dose TJL groups than in the sham operation group (ï¼»62.72 ± 9.90ï¼½% and ï¼»52.25 ± 8.15ï¼½% vs ï¼»36.53 ± 5.25ï¼½%, P < 0.01), but remarkably lower in the medium-dose TJL (ï¼»41.65 ± 4.89ï¼½%), high-dose TJL (ï¼»39.60 ± 5.19ï¼½%) and LC control (ï¼»38.33 ± 7.46ï¼½%) than in the VC+LQS model group (P < 0.01). MMP in the spermatogenic cells was significantly lower in the VC+LQS model and low-dose TJL than in the sham operation group (ï¼»34.80 ± 20.18ï¼½% and ï¼»44.39 ± 19.60ï¼½% vs ï¼»60.24 ± 22.25ï¼½%, P < 0.01 and P < 0.05), but markedly higher in the medium-dose TJL (ï¼»50.62 ± 14.83ï¼½%), high-dose TJL (ï¼»52.42 ± 7.55ï¼½%) and LC control (ï¼»50.75 ± 15.65ï¼½%) than in the VC+LQS model group (P < 0.05). The mitochondria in the spermatogenic cells of the VC+LQS model rats exhibited swelling, vacuolization, rupture or disappearance of the mitochondrial cristae, and breakdown of the internal structure. The pathological injury of the mitochondrial structure was improved in different degrees in the TJL and LC groups. CONCLUSIONS: TJL can reduce the ROS level, increase MMP and improve pathological injury of the mitochondrial ultrastructure in the spermatogenic cells of VC rats with LQS, which may be the underlying molecular mechanism of TJL improving fertility in infertile VC patients.


Assuntos
Medicamentos de Ervas Chinesas , Qi , Espermatogênese , Varicocele , Animais , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Infertilidade Masculina/terapia , Fígado , Masculino , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Modelos Animais , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Espermatogênese/efeitos dos fármacos
15.
Cancer Nurs ; 41(2): 100-108, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28410333

RESUMO

BACKGROUND: Family resilience helps family members successfully overcome adversity, for example, chronic disease or unpleasant situations. However, few studies have identified correlates of family resilience among adolescents/young adults having a parent with cancer. OBJECTIVE: This longitudinal study explored (1) relationships among family resilience, adolescents' perceived stress, and parent-adolescent/young adult communication; (2) trends in family resilience with data collection time; and (3) differences in parent-adolescent/young adult communication by parent gender (ie, father or mother). METHODS: Participants were teenagers and young adults (12-25 years) with a parent who had cancer. Data were collected using structured questionnaires at 3 times for 4 to 5 months, with 2 months between each collection. RESULTS: Of 96 adolescent/young adult participants enrolled at T1, only 32 completed all measurements at T3. We found that (1) family resilience was negatively associated with adolescents' perceived stress (B = -0.35) and positively associated with adolescent/young adult communication with both the father (B = 0.58) and the mother (B = 0.36), (2) the degree of family resilience at T3 was significantly lower than at T1 (B = -4.79), and (3) at all 3 data collection times, the degree of adolescent/young adult communication was higher with mothers than with fathers, whether the mother had cancer or did not have cancer. CONCLUSIONS: Family resilience was positively associated with parent-adolescent/young adult communication and negatively related to perceived stress. Family resilience tended to decline with longer parental survival since cancer diagnosis. IMPLICATIONS FOR PRACTICE: We suggest nursing interventions to reduce adolescent/young adult stress and develop optimal parent-adolescent/young adult communication to enhance family resilience.


Assuntos
Comportamento do Adolescente/psicologia , Comunicação , Neoplasias/psicologia , Relações Pais-Filho , Pais/psicologia , Resiliência Psicológica , Estresse Psicológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Percepção , Inquéritos e Questionários , Taiwan , Adulto Jovem
16.
Oncotarget ; 8(53): 91162-91173, 2017 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-29207633

RESUMO

Lead (Pb) is a known nephrotoxic element. Recently we have proved that subcellular Ca2+ redistribution is involved in Pb-induced apoptosis in primary cultures of rat proximal tubular (rPT) cells, but the underlying mechanism remains to be elucidated. Firstly, data showed that Pb triggers endoplasmic reticulum (ER) stress response in rPT cells, as evidenced by the elevations of ER stress markers. Moreover, pharmacological modulation of Ca2+ mobilization in ER and cytoplasm with three chemicals (2-APB or TG or BAPTA-AM) can effectively increase or decrease the protein expression of ER stress markers in Pb-exposed rPT cells, demonstrating that Pb-induced ER stress is Ca2+-dependent. We found that Pb stimulates phosphorylation of calcium/calmodulin-dependent protein kinase II (CaMKII) to activate its activity. Meanwhile, inhibition of CaMKII with KN93 or KN62 attenuated Pb-activated caspase-12 and CCAAT/enhancer-binding protein homologous protein (CHOP) in rPT cells, demonstrating that CaMKII activation promoted ER stress in rPT cells. Likewise, Pb-induced apoptosis can be effectively inhibited by CaMKII inhibitor KN93 or KN62. Furthermore, co-treatment with KN93 or KN62 significantly reversed Pb-induced ER Ca2+ release and concomitant intracellular Ca2+ overload in rPT cells. In summary, these results expound the mechanisms involving in ER stress, Ca2+ dyshomeostasis and activated CaMKII, which all contribute to Pb-induced apoptosis. CaMKII acts as a critical mediator of ER stress and associated apoptosis via regulating intracellular Ca2+ mobilization from ER to cytoplasm.

17.
Cell Death Dis ; 8(10): e3099, 2017 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-29022917

RESUMO

Autophagy has an important renoprotective function and we recently found that autophagy inhibition is involved in cadmium (Cd)-induced nephrotoxicity. Here, we aimed to investigate the protective effect of trehalose (Tre), a novel autophagy activator, against Cd-induced cytotoxicity in primary rat proximal tubular (rPT) cells. First, data showed that Tre treatment significantly decreased Cd-induced apoptotic cell death of rPT cells via inhibiting caspase-dependent apoptotic pathway, evidenced by morphological analysis, flow cytometric and immunoblot assays. Also, administration with Tre protected rPT cells against Cd-induced lipid peroxidation. Inhibition of autophagic flux in Cd-exposed rPT cells was markedly restored by Tre administration, demonstrated by immunoblot analysis of autophagy marker proteins and GFP and RFP tandemly tagged LC3 method. Resultantly, Cd-induced autophagosome accumulation was obviously alleviated by Tre treatment. Meanwhile, blockage of autophagosome-lysosome fusion by Cd exposure was noticeably restored by Tre, which promoted the autophagic degradation in Cd-exposed rPT cells. Moreover, Tre treatment markedly recovered Cd-induced lysosomal alkalinization and impairment of lysosomal degradation capacity in rPT cells, demonstrating that Tre has the ability to restore Cd-impaired lysosomal function. Collectively, these findings demonstrate that Tre treatment alleviates Cd-induced cytotoxicity in rPT cells by inhibiting apoptosis and restoring autophagic flux.


Assuntos
Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Cádmio/toxicidade , Túbulos Renais Proximais/patologia , Substâncias Protetoras/farmacologia , Trealose/farmacologia , Animais , Autofagossomos/fisiologia , Caspase 3/metabolismo , Caspase 9/metabolismo , Células Cultivadas , Túbulos Renais Proximais/citologia , Túbulos Renais Proximais/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Lisossomos/fisiologia , Estresse Oxidativo/efeitos dos fármacos , Poli(ADP-Ribose) Polimerases/metabolismo , Cultura Primária de Células , Ratos , Ratos Sprague-Dawley
18.
Zhongguo Zhong Yao Za Zhi ; 42(4): 763-771, 2017 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-28959850

RESUMO

This study aimed to analyze the endogenous metabolite changes in the serum of mice infected with H1N1 virus after intervention by Mahuang-Xixin-Fuzi decoction (MXF) based on metabolomics method, investigate potential biomarkers and related metabolic pathways, and explore the therapeutic mechanism of MXF through metabolomics technology. Thirty-six Kunming (KM) mice were randomly divided into three groups: normal group, model group and MXF group. Influenza virus H1N1 was used by nasal drip to establish influenza mice model. The mice in MXF group were orally administrated with MXF for 6 consecutive days after inoculation, and the other two groups were given with equal volume of saline solution in the same way. Body weight, rectal temperature, morbidity and mortality were recorded daily. Serum samples were collected 24 hours after the last administration for HPLC-TOF-MS analysis. The results showed that as compared with the normal group, the body weight and rectal temperature were decreased in model group, and their lung index and mortality rate were significantly increased (P<0.05); MXF had good therapeutic effects on the abnormity of body weight, rectal temperature, lung index and high mortality rate of mice infected with H1N1 virus. The original data collected from the serum samples were analyzed with R language, MPP, SIMCA-P and other software, and significant changes were found in 14 kinds of endogenous substances from mice serum (P<0.05). As compared with model group, the potential metabolic markers in MXF group recovered to normal levels to a certain degree after being intervened by MXF. Further analysis with MetPA data platform showed that, the pathways involved in 14 metabolites included glucose metabolism, arachidonic acid metabolism, glycerophospholipids and sphingolipids metabolism etc. The metabolomics study and pharmacological experiment showed that MXF might play a role of efficacy by improving glucose metabolism, regulating arachidonic acid metabolism, glycerophospholipid and sphingolipid metabolic pathways.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Metabolômica , Infecções por Orthomyxoviridae/tratamento farmacológico , Animais , Ácido Araquidônico/metabolismo , Glicerofosfolipídeos/metabolismo , Vírus da Influenza A Subtipo H1N1 , Redes e Vias Metabólicas , Camundongos , Esfingolipídeos/metabolismo
19.
Sci Rep ; 7(1): 7760, 2017 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-28798396

RESUMO

Epimedium brevicornum Maxim has a long history of use in the treatment of estrogen deficiency-related diseases. However, the chemical constituents and mechanism of action of this medicinal plant are not fully understood. In the present study, we isolated four new isoprenylated flavonoid glycosides, as well as 16 known flavonoids (13 isoprenylated flavonoids), from this plant. The chemical structures of the new flavonoid glycosides were elucidated by extensive spectroscopic analysis. The new compounds 1-4 were potent promoters of estrogen biosynthesis in human ovarian granulosa-like KGN cells. ZW1, an isoprenylated flavonoid analogue and a specific inhibitor of phosphodiesterase 5 (PDE5), was synthesized and used to explore the mechanism of the isoprenylated analogues on estrogen biosynthesis. ZW1 treatment increased estrogen production by upregulation of aromatase mRNA and protein expression. ZW1 increased the phosphorylation of cAMP response element-binding protein (CREB). Further study showed that the inhibition of PDE5 by ZW1 increased estrogen biosynthesis partly through suppression of phosphodiesterase 3 (PDE3). Our results suggested that the isoprenylated flavonoids from E. brevicornum may produce beneficial health effects through the promotion of estrogen biosynthesis. PDE5 warrants further investigation as a new therapeutic target for estrogen biosynthesis in the prevention and treatment of estrogen-deficiency related diseases.


Assuntos
Epimedium/química , Estrogênios/biossíntese , Flavonoides/farmacologia , Glicosídeos/farmacologia , Células da Granulosa/efeitos dos fármacos , Inibidores de Fosfodiesterase/farmacologia , Linhagem Celular , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Feminino , Flavonoides/química , Glicosídeos/química , Células da Granulosa/metabolismo , Humanos , Inibidores de Fosfodiesterase/química , Plantas Medicinais/química
20.
Nat Prod Res ; 31(19): 2250-2255, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28281370

RESUMO

One new tirucallane-type nortriterpenoid Nortirucallane A (1), together with Chrysoeriol (2) and Isorhamnetin (3), was isolated from the methylene chloride part of Lonicerae japonicae flos. Their structures were elucidated by the detailed analysis of comprehensive spectroscopic data. Compound 3 was isolated from the genus of Lonicera for the first time. The significance of 1 for the study of phytochemical taxonomy was discussed.


Assuntos
Lonicera/química , Triterpenos/isolamento & purificação , Classificação , Flores/química , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Análise Espectral , Triterpenos/química
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...