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1.
Ying Yong Sheng Tai Xue Bao ; 34(10): 2845-2853, 2023 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-37897293

RESUMO

Allergenic airborne pollen can induce hay fever such as rhinitis and asthma. Many studies have been conducted on the allergenic pollution caused by airborne pollen. We synthesized available studies to summarize the temporal and spatial distributions of airborne pollen and influencing meteorological factors. We further summarized and discussed the hazards of airborne pollen sensitization on human health and evaluation indicators for classifying hazard levels. We described the research progress of prevention and control measures of airborne pollen induced pollution from the perspectives of source control, route monitoring, and prevention of susceptible population. Considering the limitations of current studies, we proposed some research directions on allergenic airborne pollen. The types of allergenic plants needed to be clearly identified and allergentic potential should be quantitatively identified. The methods of pollen collection and concentration monitoring needed to be improved and standardized. This review could provide a scientific guidance for the study on preventing and treating pollen allergies as well as optimizing urban green space planning.


Assuntos
Alérgenos , Rinite Alérgica Sazonal , Humanos , Pólen , Rinite Alérgica Sazonal/etiologia , Rinite Alérgica Sazonal/prevenção & controle , Plantas , Conceitos Meteorológicos , Monitoramento Ambiental/métodos
2.
Huan Jing Ke Xue ; 44(9): 4954-4964, 2023 Sep 08.
Artigo em Chinês | MEDLINE | ID: mdl-37699813

RESUMO

The typical river-lake ecotone (tail end area) of Poyang Lake, which is a sensitive area and prone to outbreaks of cyanobacteria bloom, is vulnerable to frequent human activities. To explore the diversity of phytoplankton community structure and the relevant driving mechanism in the typical river lake junction area of Poyang Lake, the water quality and phytoplankton at seven sampling points in the typical river lake junction area of Poyang Lake, at six sampling points in the middle section of Poyang Lake River, and at one sampling point in the main lake area were investigated in the field from 2019 to 2020 (dry season), April (flood season), July (wet season), and October (recession period). The results showed that there were seven phyla and 64 genera of phytoplankton in the typical river-lake ecotone of Poyang Lake, and the biomass and relative abundance of phytoplankton were dominated by diatoms and cyanobacteria. The biomass and abundance in the east of the typical river-lake ecotone of Poyang Lake were generally higher than those in the west, and the biomass and abundance in the river-lake ecotone were higher than those in the middle of the river. The dominant degree of cyanobacteria in the lake area and the river-lake ecotone was large, and the dominant degree of diatoms in the middle section of the river was large. The Monte Carlo test results showed that total nitrogen (TN), total phosphorus (TP), orthophosphate phosphorus (PO43--P), water depth (WD), water temperature (WT), and transparency (SD) were significantly related environmental factors affecting the distribution of the phytoplankton community. Redundancy analysis results showed that the typical river-lake ecotone in the west of Poyang Lake was highly affected by the hydration factors (TN, TP, and PO43--P), and the hydrological factors (WT, WD, and SD) in the typical river-lake ecotone in the east were highly significant. The impact factors of phytoplankton in the typical river-lake ecotone of Poyang Lake were seasonal, being greatly affected by hydration factors in winter and hydrological factors in summer.


Assuntos
Diatomáceas , Fitoplâncton , Humanos , Rios , Biomassa , Nitrogênio , Fósforo
3.
Sci Prog ; 106(1): 368504221147173, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36718538

RESUMO

Colorectal cancer (CRC) can be resistant to platinum drugs, possibly through ferroptosis suppression, albeit the need for further work to completely understand this mechanism. This work aimed to sum up current findings pertaining to oxaliplatin resistance (OR) or resistance to ascertain the potential of ferroptosis to regulate oxaliplatin effects. In this review, tumor development relating to iron homeostasis, which includes levels of iron that ascertain cells' sensitivity to ferroptosis, oxidative stress, or lipid peroxidation in colorectal tumor cells that are connected with ferroptosis initiation, especially the role of c-Myc/NRF2 signaling in regulating iron homeostasis, coupled with NRF2/GPX4-mediated ferroptosis are discussed. Importantly, ferroptosis plays a key role in OR and ferroptotic induction may substantially reverse OR in CRC cells, which in turn could inhibit the imbalance of intracellular redox induced by oxaliplatin and ferroptosis, as well as cause chemotherapeutic resistance in CRC. Furthermore, fundamental research of small molecules, ferroptosis inducers, GPX4 inhibitors, or natural products for OR coupled with their clinical applications in CRC have also been summarized. Also, potential molecular targets and mechanisms of small molecules or drugs are discussed as well. Suggestively, OR of CRC cells could significantly be reversed by ferroptosis induction, wherein this result is discussed in the current review. Prospectively, the existing literature discussed in this review will provide a solid foundation for scientists to research the potential use of combined anticancer drugs which can overcome OR via targeting various mechanisms of ferroptosis. Especially, promising therapeutic strategies, challenges ,and opportunities for CRC therapy will be discussed.


Assuntos
Neoplasias Colorretais , Ferroptose , Humanos , Platina/farmacologia , Oxaliplatina/farmacologia , Oxaliplatina/uso terapêutico , Fator 2 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/farmacologia , Procedimentos Clínicos , Ferro/metabolismo , Ferro/farmacologia , Neoplasias Colorretais/tratamento farmacológico
4.
Plant Biotechnol J ; 20(10): 2023-2035, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35781755

RESUMO

Thermosensitive genic male sterility (TGMS) lines serve as the major genetic resource for two-line hybrid breeding in rice. However, their unstable sterility under occasional low temperatures in summer highly limits their application. In this study, we identified a novel rice TGMS line, ostms18, of cultivar ZH11 (Oryza sativa ssp. japonica). ostms18 sterility is more stable in summer than the TGMS line carrying the widely used locus tms5 in the ZH11 genetic background, suggesting its potential application for rice breeding. The ostms18 TGMS trait is caused by the point mutation from Gly to Ser in a glucose-methanol-choline (GMC) oxidoreductase; knockout of the oxidoreductase was previously reported to cause complete male sterility. Cellular analysis revealed the pollen wall of ostms18 to be defective, leading to aborted pollen under high temperature. Further analysis showed that the tapetal transcription factor OsMS188 directly regulates OsTMS18 for pollen wall formation. Under low temperature, the flawed pollen wall in ostms18 is sufficient to protect its microspore, allowing for development of functional pollen and restoring fertility. We identified the orthologous gene in Arabidopsis. Although mutants for the gene were fertile under normal conditions (24°C), fertility was significantly reduced under high temperature (28°C), exhibiting a TGMS trait. A cellular mechanism integrated with genetic mutations and different plant species for fertility restoration of TGMS lines is proposed.


Assuntos
Arabidopsis , Oryza , Oxirredutases , Infertilidade das Plantas , Pólen , Arabidopsis/genética , Arabidopsis/fisiologia , Colina/metabolismo , Glucose/metabolismo , Metanol/metabolismo , Mutação , Oryza/genética , Oryza/fisiologia , Oxirredutases/genética , Infertilidade das Plantas/genética , Pólen/genética , Pólen/crescimento & desenvolvimento , Temperatura , Fatores de Transcrição/genética
5.
Mol Plant ; 14(12): 2104-2114, 2021 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-34464765

RESUMO

During anther development, the transformation of the microspore into mature pollen occurs under the protection of first the tetrad wall and later the pollen wall. Mutations in genes involved in this wall transition often lead to microspore rupture and male sterility; some such mutants, such as the reversible male sterile (rvms) mutant, are thermo/photoperiod-sensitive genic male sterile (P/TGMS) lines. Previous studies have shown that slow development is a general mechanism of P/TGMS fertility restoration. In this study, we identified restorer of rvms-2 (res2), which is an allele of QUARTET 3 (QRT3) encoding a polygalacturonase that shows delayed degradation of the tetrad pectin wall. We found that MS188, a tapetum-specific transcription factor essential for pollen wall formation, can activate QRT3 expression for pectin wall degradation, indicating a non-cell-autonomous pathway involved in the regulation of the cell wall transition. Further assays showed that a delay in degradation of the tetrad pectin wall is responsible for the fertility restoration of rvms and other P/TGMS lines, whereas early expression of QRT3 eliminates low temperature restoration of rvms-2 fertility. Taken together, these results suggest a likely cellular mechanism of fertility restoration in P/TGMS lines, that is, slow development during the cell wall transition of P/TGMS microspores may reduce the requirement for their wall protection and thus support their development into functional pollens, leading to restored fertility.


Assuntos
Proteínas de Arabidopsis/genética , Arabidopsis/genética , Fotoperíodo , Infertilidade das Plantas/genética , Infertilidade das Plantas/fisiologia , Arabidopsis/crescimento & desenvolvimento , Proteínas de Arabidopsis/metabolismo , Parede Celular/fisiologia , Temperatura Baixa , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Mutação , Pólen/genética , Pólen/fisiologia
6.
Nutr Cancer ; 72(2): 293-319, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31267795

RESUMO

Background: Rhus chinensis Mill is a traditional Chinese medicine (TCM) mostly used to treat several cancer types. Although previous studies have found that certain ingredients of R. chinensis such as flavonoids can inhibit tumor cell proliferation [e.g. colorectal cancer (CRC)], systematic research on the mechanism underlying anticancer effect of active compounds like triterpenoids (TER) is lacking.Study Design: Herein, the concept of "network pharmacology primarily based on active compounds" was applied to explore the anticancer mechanisms of TER extract from R. chinensis. In this regard, potential targets and pathways of glycolysis and glutaminolysis form the basis for the anti-CRC effect of triterpenoids. Network pharmacology was used to predict several key proteins in the metabolic pathways, which were further verified via western blot and metabolomics methods.Results: Our results showed that the total TER in R. chinensis remarkably inhibited the proliferation and apoptosis of SW620 cells. The top 4 compounds of TER (viz., betulinic acid-BTA, betulonic acid-BTOA, betulin-BT, and semialactic acid-SA) were confirmed through the detection of UPLC-MS and analysis of cell proliferation assays. Mechanistically, this study revealed that TER plays an anti-CRC role through key targets, such as ENO1, ALDOA, PFKFB3, PKM2, and LDHA, as well as key glycolytic and glutaminolytic pathways.Conclusion: Collectively, these results have provided new insights into the mechanism underlying anti-CRC effect of triterpenoids extract obtained from R. chinensis, mainly through combination of compositional quantitative analysis, network pharmacology, and experimental verification.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Redes Reguladoras de Genes , Glutamina/metabolismo , Glicólise , Rhus/química , Triterpenos/farmacologia , Animais , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Cromatografia Líquida , Neoplasias Colorretais/enzimologia , Neoplasias Colorretais/patologia , Flavonoides/farmacologia , Humanos , Masculino , Metaboloma/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Triterpenos Pentacíclicos/farmacologia , Extratos Vegetais/farmacologia , Espectrometria de Massas em Tandem , Estudos de Validação como Assunto , Ensaios Antitumorais Modelo de Xenoenxerto , Ácido Betulínico
7.
J Ethnopharmacol ; 235: 255-267, 2019 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-30772482

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Studies have shown that the etiology and pathogenesis of colorectal cancer are closely related to the tumor microenvironment, and the cancer tissue is still in the state of "energy deficit" and has to promote energy generation through high glycolysis. Rhus chinensis Mill is a Chinese herbal medicine used to treat various types of solid tumors in China. Colorectal cancer (CRC) is a heterogeneous disease group caused by abnormal changes in glucose metabolism resulted in lactic acid production, which remodels acidosis. AIM OF THE STUDY: Although previous studies have shown that the active compounds of Rhus chinensis Mill. can inhibit the proliferation of tumor cells, whether its triterpenoids could effectively regulate glycolysis involved in CRC have not been systematically investigated. MATERIALS AND METHODS: In this study, the extraction of triterpenoids extract from Rhus chinensis Mill. was obtained, and cell viability assay, the percentage of apoptosis for CRC cells were counted, and matrigel invasion assay and production of lactic acid and glucose uptake assay was determined. we further examined the expression of the key glycolytic enzymes and acid-sending ion channel (ASIC) family members of SW620 cells, and some key proteins in the glycolytic pathway were further verified. RESULTS: Notably, triterpenoids (TER) of Rhus chinensis Mill. showed effective anti-proliferative activity and significantly altered protein levels associated with CRC cell survival and glycolysis metabolism. TER could down-regulate the expression of ASIC2, in CRC SW620 cell line. Most importantly, the levels of ASIC2 and calcineurin/nuclear factor of activated T cells (NFAT) were also down-regulated by TER. Furthermore, inhibition of activated the ASIC2-mediated calcineurin/NFAT1 pathway and target gene transcript expression of MMP-2 and MMP-9 in parallel to reduce, and resulted in the reduced invasion ability by TER treatment. CONCLUSION: The potential pathways and targets that involved in glycolysis to excert the anti-CRC effects of main compounds in triterpenoids of Rhus chinensis Mill. were predicted by network pharmacology methods. Our findings thus provided rational evidence that inhibition of the ASIC2-induced calcineurin/NFAT pathway by triterpenoids in Rhus chinensis Mill. profoundly suppressed cell growth and invasion in CRC, which target alternative glycolysis in colorectal tumor cells, may be a useful adjuvant therapy in the treatment of colorectal cancer.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Rhus/química , Triterpenos/farmacologia , Canais Iônicos Sensíveis a Ácido/metabolismo , Antineoplásicos Fitogênicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Calcineurina/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Neoplasias Colorretais/patologia , Regulação para Baixo/efeitos dos fármacos , Glicólise/efeitos dos fármacos , Humanos , Medicina Tradicional Chinesa/métodos , Fatores de Transcrição NFATC/metabolismo , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Triterpenos/isolamento & purificação , Microambiente Tumoral
8.
Artigo em Chinês | WPRIM | ID: wpr-712679

RESUMO

Objective:To investigate the analgesic time-effect characteristics and changes in concentrations of rabbit's hypothalamic 5-hydroxytryptamine (5-HT) and noradrenaline (NE) caused by buccal acupuncture in the rheumatoid arthritis (RA) rabbits,and to reveal the analgesic central mechanism of buccal acupuncture,thereby providing a theoretical basis for the treatment of pain by buccal acupuncture.Methods:Forty rabbits were randomly divided into a normal group,a model group,a body acupuncture group,and a buccal acupuncture group,with 10 rabbits in each group.No model was established in the normal group,while equal dose of normal saline was injected at the matched site and time point;rabbits in other groups were subjected to the establishment of RA models using egg protein.From the 27th day of the experiment,rabbits in each group received the designated intervention.Rabbits in the normal group and the model group were fixed for 30 min every day using the same method as those in the other groups.In the acupuncture group,Dubi (ST 35) and Zusanli (ST 36) on bilateral hind limbs were selected.Perpendicular needling (using the needles with 0.25 mm in diameter and 25 mm in length) was performed with twirling manipulation for 15 s at intervals of 5 min.The needles were retained for 30 min and acupuncture was performed once a day.In the buccal acupuncture group,the knee point in the buccal acupuncture and needles with a diameter of 0.25 mm and a length of 15 mm were selected.Oblique needling was performed with twirling manipulation for 15 s at intervals of 5 min.The needles were retained for 30 min and acupuncture was performed once a day.The thermal pain thresholds at the 0,5,15,30,60,120 and 240 min after the 1st and 10th acupuncture therapy were measured with a PL-200 thermal-inducing pain meter.After the 10th acupuncture therapy,rabbit's hypothalamus was removed,and the 5-HT and NE concentrations in the hypothalamus at the peak point of the acupuncture pain threshold curve were determined by high performance liquid chromatography (HPLC).Results:The analgesic effect was obvious at 5 min after buccal acupuncture started,peaked at 30 min,and decreased to the lowest value at 240 min.Rabbits in the body acupuncture group began to show significant analgesic effect at 15 min,which was peaked at 30 min,and began to decline at 60 min.The pain threshold at 240 min was still higher than that at 0 min.Compared with the model group,the concentrations of hypothalamic 5-HT in the buccal acupuncture group and the body acupuncture group was significantly increased,and the between-group differences were statistically significant (both P<0.05).The NE/5-HT ratios in hypothalamus in the buccal acupuncture group and the body acupuncture group were significantly lower than the ratio in the model group,and the differences were statistically significant (both P<0.05);difference in the decrease was statistically significant between the buccal acupuncture group and the body acupuncture group (P<0.05).Conclusion:The analgesic effect of buccal acupuncture shows an obvious time-dependent curve.It is characterized by rapid onset of pain relief,rapid increase and decline in pain threshold.5-HT and NE levels in rabbit's hypothalamus can be affected by buccal acupuncture,with increased 5-HT concentration and reduced NE/5-HT ratio.

9.
Nutr Cancer ; 68(8): 1357-1368, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27673410

RESUMO

This proposal seeks to study the potential therapeutic modality of chemoprevention and anticancer effects and mechanisms of the flavonoids from Cotinus coggygria Scop. on glioblastoma cancer. In the current study, the total flavonoids (TFs) isolated from Cotinus coggygria Scop. var. cinerea Engl. (Cotinus coggygria Scop.) and the major flavonoids of Cotinus coggygria Scop. (CCFs) were identified, and the inhibitory kinetics of TF and CCF on glioblastoma cell lines were calculated. We also investigated whether TF or CCF regulated the apoptotic mechanism in cellular models of glio-blastoma cells. Finally, we evaluated whether treatment with TF or CCF suppressed tumor growth and inhibited migration in orthotopic mouse models of glioblastoma in vivo. In this study, the CCFs were identified as rutin, myricetin, and fisetin. TF and CCF remarkably inhibited cell proliferation and downregulated the PI3K/Akt and ERK signaling pathway in glioblastoma cell lines. Furthermore, the mitochondrial caspase-dependent cascade was regulated by TF and myricetin. In addition, TF and myricetin exhibited significant antitumor effects on glioblastoma in vivo. Taken together, these results suggest that phytochemical and biological data provide evidence for the active components in Cotinus coggygria, and that the TFs are responsible for the anticancer effects on glioblastoma cell growth via induction of apoptosis. In addition, the representative compound myricetin could provide a clinically relevant therapeutic opportunity. Therefore, our data strongly suggest that myricetin-deprived CCF can serve as a potent chemopreventive herbal medicine.


Assuntos
Anacardiaceae/química , Antineoplásicos Fitogênicos/farmacologia , Flavonoides/farmacologia , Glioblastoma/tratamento farmacológico , Animais , Antineoplásicos Fitogênicos/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Feminino , Flavonoides/análise , Flavonoides/química , Humanos , Cinética , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Camundongos Nus , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
10.
Am J Chin Med ; 41(4): 801-15, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23895153

RESUMO

The lignan extracts from the tree bark of Eucommia ulmoides Oliv., a famous traditional Chinese medicine, have been demonstrated to have inhibitory effects on aldose reductase activity in spontaneously hypertensive rat myocardium. This study was aimed to investigate the hypertensive cardiac remodeling effects of the lignan extracts together with epalrestat. Ten-week-old male spontaneously hypertensive rats were randomly divided into three groups (n = 12, each) and administered 100 mg/kg/d of captopril (angiotensin converting enzyme inhibitor), 100 mg/kg/d of epalrestat (aldose reductase inhibitor) or 300 mg/kg/d of lignan extracts by gavage for 16 weeks. Sex-, age-, and number-matched normotensive Wistar Kyoto rats with spontaneously hypertensive rats were treated with distilled water (vehicle) as controls. Systolic blood pressures were measured periodically. Echocardiography examination was taken when rats were 24 weeks old. We found that both captopril and lignan extracts lowered blood pressure, and inhibited aldose reductase activity similarly to epalrestat. Echocardiography examination and histomorphometry indices were improved in all treated groups (p < 0.05). Therefore, lignan extracts could prevent hypertensive cardiac remodeling, which is likely related to aldose reductase inhibition.


Assuntos
Aldeído Redutase/antagonistas & inibidores , Eucommiaceae , Lignanas/farmacologia , Casca de Planta , Extratos Vegetais/farmacologia , Remodelação Ventricular/efeitos dos fármacos , Aldeído Redutase/efeitos dos fármacos , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Captopril/farmacologia , Masculino , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Rodanina/análogos & derivados , Rodanina/farmacologia , Tiazolidinas/farmacologia
11.
J Ethnopharmacol ; 139(2): 454-61, 2012 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-22138658

RESUMO

AIM OF THE STUDY: To investigate the protective effects and the underlying mechanism of Eucommia lignans against hypertensive renal injury. MATERIAL AND METHODS: Ten-week-old Wistar Kyoto rats and age matched spontaneously hypertension rats were used in the study. The SHR were randomly divided into 4 groups (n=7 for each group) and received different treatment for 16 weeks, which including saline, Captopril, Epalrestat and Eucommia lignans, respectively. System blood pressures of the rats were monitored once every 4 weeks. N-Acetyl-ß-D-glucosaminidase (NAG) activity and the ratio of albumin and urinary creatinine were chosen as the indices of kidney function. Then the structure and renal collagen type III expression of glomerular basement membrane were observed by microscopy and the renal aldose reductase (AR) expression was measured by immunohistochemistry. In vitro, the proliferation of mesangial cells induced by AngII was assayed by MTT, and the mRNA expression of AR was measured by RT-real-time PCR. RESULTS: The renal function, evaluated by NAG enzyme activity and the ratio of albumin to urinary creatinine, was significantly ameliorated by Eucommia lignans treatment. Meanwhile, Eucommia lignans decreased both the protein (P<0.05) and the mRNA expressed lever of AR (P<0.05). Eucommia lignans also decreased the high expression of collagen type III in SHR (P<0.05) and inhibited the proliferation of renal mesangial cells induced by AngII (P<0.05). CONCLUSION: Eucommia lignans have protective effects against hypertensive renal injury, and the protective effects may be partly due to inhibition of aldose reductase.


Assuntos
Aldeído Redutase/antagonistas & inibidores , Anti-Hipertensivos/farmacologia , Inibidores Enzimáticos/farmacologia , Eucommiaceae , Hipertensão/tratamento farmacológico , Nefropatias/prevenção & controle , Rim/efeitos dos fármacos , Lignanas/farmacologia , Extratos Vegetais/farmacologia , Acetilglucosaminidase/urina , Albuminúria/enzimologia , Albuminúria/etiologia , Albuminúria/prevenção & controle , Aldeído Redutase/genética , Aldeído Redutase/metabolismo , Animais , Anti-Hipertensivos/isolamento & purificação , Biomarcadores/urina , Pressão Sanguínea/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Colágeno Tipo III/metabolismo , Creatinina/urina , Modelos Animais de Doenças , Regulação para Baixo , Inibidores Enzimáticos/isolamento & purificação , Eucommiaceae/química , Membrana Basal Glomerular/efeitos dos fármacos , Membrana Basal Glomerular/enzimologia , Membrana Basal Glomerular/patologia , Hipertensão/complicações , Hipertensão/enzimologia , Hipertensão/fisiopatologia , Imuno-Histoquímica , Rim/enzimologia , Rim/patologia , Rim/fisiopatologia , Nefropatias/enzimologia , Nefropatias/etiologia , Nefropatias/fisiopatologia , Lignanas/isolamento & purificação , Masculino , Extratos Vegetais/isolamento & purificação , Plantas Medicinais , RNA Mensageiro/metabolismo , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Fatores de Tempo
12.
Oncol Rep ; 26(5): 1181-7, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21811764

RESUMO

Acetylbritannilactone (ABL) is a new active compound isolated from Inula Britannica L, a traditional Chinese medicinal herb. It has been reported that ABL can inhibit the proliferation of vascular smooth muscle cells (VSMCs) and neointima formation after balloon injury in rats. ABL also shows chemopreventive properties by inducing cell apoptosis in breast and ovarian cancers, but the antitumor activity and the molecular targets of ABL in colon cancer cells have not been determined. In this study, we showed that ABL inhibits the growth in dose- and time-dependent manners by inducing cell cycle arrest in G0/G1 phase of HT-29 human colon cancer cells. This suppression was accompanied by a strong decrease of cyclin E and CDK4 protein levels, and an increase in p21 protein expression in HT-29 cells. We also show that ABL-induced growth inhibition is associated with the upregulation of KLF4 expression. The overexpression of KLF4 by infection with pAd-KLF4 resulted in growth inhibition, with decrease in the protein levels of cyclin E and CDK4, and increase in the expression of p21, similarly to the effects of ABL. Conversely, knockdown of KLF4 using a specific siRNA impaired the ABL-induced growth inhibition in HT-29 cells. These results suggest that KLF4 as an important cellular target of ABL mediates the growth inhibition of HT-29 cells induced by ABL via upregulation of p21 expression.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Fatores de Transcrição Kruppel-Like/biossíntese , Lactonas/farmacologia , Animais , Ciclo Celular/efeitos dos fármacos , Processos de Crescimento Celular/efeitos dos fármacos , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Inibidor de Quinase Dependente de Ciclina p21/biossíntese , Inibidor de Quinase Dependente de Ciclina p21/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células HT29 , Humanos , Fator 4 Semelhante a Kruppel , Fatores de Transcrição Kruppel-Like/genética , Camundongos , Ratos , Regulação para Cima/efeitos dos fármacos
13.
J Ethnopharmacol ; 133(1): 6-13, 2011 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-20817083

RESUMO

AIM OF THE STUDY: To investigate the effects of lignans extracted from Eucommia ulmoides and epalrestat on vascular remodeling in spontaneously hypertensive rats. MATERIALS AND METHODS: Ten-week-old male spontaneously hypertensive rats were randomly divided into 3 groups (12 rats each group), and treated orally with 100 mg/kg/d of captopril (an angiotensin-converting enzyme inhibitor), 100 mg/kg/d of epalrestat (an aldose reductase inhibitor) and 300 mg/kg/d of lignans by gavage daily for 16 weeks, respectively. Sex-, age-, and number-matched spontaneously hypertensive rats and normotensive Wistar Kyoto rats, were treated with distilled water (vehicle) as controls. The rats were weighed weekly. Mean arterial blood pressure and heart rate were measured periodically by non-invasive blood pressure monitoring. They were sacrificed at the end of experiment (26-week-old). Superior mesenteric artery and aorta were isolated for determination of histomorphometry and the expression of aldose reductase by immunohistochemistry. RESULTS: Captopril and lignans, but not epalrestat, decreased mean arterial blood pressure in spontaneously hypertensive rats. Vascular remodeling was improved in all three treated groups by histomorphometry. CONCLUSIONS: Both lignans and epalrestat reversed hypertensive vascular remodeling. Aldose reductase played a vital role in the pathologic process of hypertensive vascular remodeling rather than elevation of blood pressure. These data suggested that aldose reductase could be a new therapeutic target for the treatment of cardiovascular diseases.


Assuntos
Aldeído Redutase/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Eucommiaceae , Hipertensão/tratamento farmacológico , Hipertensão/patologia , Lignanas/farmacologia , Rodanina/análogos & derivados , Tiazolidinas/farmacologia , Aldeído Redutase/metabolismo , Animais , Aorta/enzimologia , Aorta/patologia , Pressão Sanguínea/efeitos dos fármacos , Captopril/farmacologia , Medicamentos de Ervas Chinesas , Feminino , Frequência Cardíaca/efeitos dos fármacos , Hipertensão/enzimologia , Masculino , Artéria Mesentérica Superior/enzimologia , Artéria Mesentérica Superior/patologia , Casca de Planta , Distribuição Aleatória , Ratos , Ratos Endogâmicos SHR , Ratos Wistar , Rodanina/farmacologia
14.
Int J Cardiol ; 149(1): 30-8, 2011 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-20060605

RESUMO

BACKGROUND: The present study was designed to determine the effects of Acetylbritannilactone (ABL), a naturally occurring Inula britannica L., on vascular smooth muscle cell (VSMC) proliferation and apoptosis. METHODS: In vitro experiments were performed to evaluate the effects of ABL on the VSMC cycle and apoptosis stimulated by chemoattractant. In addition, to examine the effects of ABL in vivo, balloon injury to rat carotid arteries was performed. RESULTS: ABL treatment inhibited platelet-derived growth factor (PDGF) induced DNA synthesis and proliferation in cultured VSMC. Such growth-inhibitory effects of ABL were associated with G1 phase arrest, which were correlated with reduction of cyclins D1, A, and E expression and cyclin-dependent kinase (CDK) 2, CDK4, and CDK6 proteins, increased the CDK inhibitory protein p21cip1 expression, and enhanced the binding of p21cip1 to CDKs. In addition, ABL also induced apoptosis in proliferative VSMCs, as evidenced by the induction of a higher ratio of Bax/Bcl-2, activation of caspase-9, caspase-3, and the cleavage of endogenous substrate Poly (ADP-ribose) polymerase. However, pretreatment with pan-caspases inhibitor (z-VAD-fmk) only partially reversed ABL-induced apoptosis, suggesting the involvement of both caspase-dependent and caspase-independent pathways in these processes. Furthermore, the effects of ABL on VSMCs were associated with the downregulation of extracellular signal-regulated kinase (ERK) 1/2 signaling pathways. In vivo, ABL (26 mg/kg/day) significantly suppressed injury-induced ERK1/2 phosphorylation, and increased VSMC apoptosis 14 days after balloon injury. CONCLUSIONS: Our findings demonstrated that ABL was capable of suppressing the abnormal VSMC proliferation, accompanied by the induction of apoptosis in vivo and in vitro. It suggested that ABL could be considered a pharmacological candidate for the prevention of restenosis after balloon angioplasty.


Assuntos
Apoptose/efeitos dos fármacos , Fase G1/efeitos dos fármacos , Lactonas/farmacologia , Músculo Liso Vascular/citologia , Músculo Liso Vascular/efeitos dos fármacos , Angioplastia com Balão/efeitos adversos , Animais , Aorta Torácica/citologia , Apoptose/fisiologia , Lesões das Artérias Carótidas/tratamento farmacológico , Lesões das Artérias Carótidas/patologia , Divisão Celular/efeitos dos fármacos , Divisão Celular/fisiologia , Movimento Celular/efeitos dos fármacos , Movimento Celular/fisiologia , Células Cultivadas , Inibidor de Quinase Dependente de Ciclina p21/genética , Quinases Ciclina-Dependentes/antagonistas & inibidores , Ciclinas/antagonistas & inibidores , Modelos Animais de Doenças , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Fase G1/fisiologia , Inula , Masculino , Preparações de Plantas/farmacologia , Ratos , Ratos Sprague-Dawley , Receptores do Fator de Crescimento Derivado de Plaquetas/metabolismo
15.
Mol Biol Rep ; 37(3): 1591-6, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19455404

RESUMO

Annexin B2 (AnxB2) is a novel member of the annexin family of Ca(2+)- and phospholipid-binding proteins from Cysticercus cellulosae. To obtain highly pure AnxB2 with an easy and inexpensive purification approach, its cDNA was cloned into the prokaryotic expression vector pJLA503 and the translation initiation codon was immediately under the control of the inducible bacteriophage lambda promoters P(R) and P(L). After induction by shifting temperature, large amounts of non-fusion protein were produced in Escherichia coli in a soluble form. Then a novel purification method based on Ca(2+)-dependent phosphatidylserine (PS)-binding activity was established, whereby the purity of AnxB2 was increased to 98.7%. Western blot analysis showed that recombinant AnxB2 was specifically recognized by serum of pigs infected with cysticercosis. In vitro test showed that, the recombinant AnxB2 had anticoagulant activity and platelet binding activity. The expression, purification, and initial characterization of AnxB2 set an important stage for further characterization of the protein.


Assuntos
Anexinas/genética , Proteínas de Ligação ao Cálcio/genética , Cysticercus/genética , Proteínas de Helminto/genética , Sequência de Aminoácidos , Animais , Anexinas/metabolismo , Bacteriófago lambda , Western Blotting , Proteínas de Ligação ao Cálcio/metabolismo , Cromatografia Líquida de Alta Pressão , Clonagem Molecular , Primers do DNA/genética , DNA Complementar/genética , Eletroforese em Gel de Poliacrilamida , Escherichia coli , Vetores Genéticos , Proteínas de Helminto/metabolismo , Dados de Sequência Molecular , Análise de Sequência de Proteína
16.
J Exp Clin Cancer Res ; 28: 12, 2009 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-19175942

RESUMO

BACKGROUND: To investigate the effectiveness and mechanism of 125I seed continuous low-dose-rate irradiation on colonic cell line CL187 in vitro. METHODS: The CL187 cell line was exposed to radiation of 60Cogamma ray at high dose rate of 2 Gy/min and 125I seed at low dose rate of 2.77 cGy/h. Radiation responses to different doses and dose rates were evaluated by colony-forming assay. Under 125I seed low dose rate irradiation, a total of 12 culture dishes were randomly divided into 4 groups: Control group, and 2, 5, and 10 Gy irradiation groups. At 48 h after irradiation, apoptosis was detected by Annexin and Propidium iodide (PI) staining. Cell cycle arrests were detected by PI staining. In order to investigate the influence of low dose rate irradiation on the MAPK signal transduction, the expression changes of epidermal growth factor receptor (EGFR) and Raf under continuous low dose rate irradiation (CLDR) and/or EGFR monoclonal antibodies were determined by indirect immunofluorescence. RESULTS: The relative biological effect (RBE) for 125I seeds compared with 60Co gamma ray was 1.41. Apoptosis rates of CL187 cancer cells were 13.74% +/- 1.63%, 32.58% +/- 3.61%, and 46.27% +/- 3.82% after 2 Gy, 5 Gy, and 10 Gy irradiation, respectively; however, the control group apoptosis rate was 1.67% +/- 0.19%. G2/M cell cycle arrests of CL187 cancer cells were 42.59% +/- 3.21%, 59.84% +/- 4.96%, and 34.61% +/- 2.79% after 2 Gy, 5 Gy, and 10 Gy irradiation, respectively; however, the control group apoptosis rate was 26.44% +/- 2.53%. P < 0.05 vs. control groups by Student's t-test were found in every treated group both in apoptosis and in G2/M cell cycle arrest. After low dose rate irradiation, EGFR and Raf expression increased, but when EGFR was blocked by a monoclonal antibody, EGFR and Raf expression did not change. CONCLUSION: 125I seeds resulted in more effective inhibition than 60Co gamma ray high dose rate irradiation in CL187 cells. Apoptosis following G2/M cell cycle arrest was the main mechanism of cell-killing effects under low dose rate irradiation. CLDR could influence the proliferation of cells via MAPK signal transduction.


Assuntos
Apoptose/efeitos da radiação , Ciclo Celular/efeitos da radiação , Neoplasias do Colo/radioterapia , Radioisótopos do Iodo/administração & dosagem , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/farmacologia , Apoptose/efeitos dos fármacos , Braquiterapia , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos da radiação , Neoplasias do Colo/enzimologia , Neoplasias do Colo/patologia , Relação Dose-Resposta à Radiação , Receptores ErbB/biossíntese , Receptores ErbB/imunologia , Humanos , Doses de Radiação , Quinases raf/biossíntese
17.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 25(2): 268-72, 2009 May.
Artigo em Chinês | MEDLINE | ID: mdl-21189569

RESUMO

AIM: To investigate the effects of glutamine on the colonic mucosa of mice subjected to colitis gravis. METHODS: 64 Kunming mice were divided randomly into 4 groups (n=16): healthy group: animals not subjected to colitis; model group: animals subjected to colitis gravis but without glutamine supplementation; low-Gln group: animals subjected to colitis gravis and with low dose of glutamine supplementation; high-Gln group: animals subjected to colitis gravis and with high dose of glutamine supplementation. Animals belonging to the control, the low-Gln, the high-Gin groups were subjected to coloclysis by HAC to be colitis gravis animals. When the models were established, the healthy and the control groups were given some isotonic Na chloride by intragastric administration. The low-Gln group and the high-Gln group were given the same volume but different concentration of glutamine(low-Gln group--2 mmol x Kg(-1) bw, high-Gln group--2 mmol x Kg(-1) bw) for 7 days. Then the mice were sacrificed, the pathohistological changes of the colon were observed, besides, the content of endotoxin in the blood serum, the level of counteracting oxidation and the activities of MPO of the colon tissue were determined. RESULTS: The glutamine lessened the pathological injures in the colon and relieved the step up of the content of endotoxin in the blood serum , the step down level of counteracting oxidation and the step up activity of MPO in the colon tissue, which were caused by colitis gravis. CONCLUSION: The glutamine can protect the colon of mice subjected to colitis gravis.


Assuntos
Colite Ulcerativa/tratamento farmacológico , Colo/patologia , Glutamina/uso terapêutico , Ácido Acético , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/patologia , Feminino , Glutamina/farmacologia , Masculino , Camundongos , Distribuição Aleatória
18.
Zhongguo Zhong Yao Za Zhi ; 32(24): 2585-7, 2007 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-18338591

RESUMO

The advances in the research on pharmacological activities of aucubin have been summarized in the last ten years. Aucubin is one of active components of Chinese medicinal herbs such as Eucommia ulmoides and has been shown wide pharmacological activities including hepatoproective, antitoxicanti-inflammatory, antioxidant, antiaging, antiosteoporosis and neurotrophic and should be further researched and utilized.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Eucommiaceae , Glucosídeos/farmacologia , Iridoides/farmacologia , Piranos/farmacologia , Envelhecimento/efeitos dos fármacos , Animais , Eucommiaceae/química , Glucosídeos/química , Glucosídeos/isolamento & purificação , Glucosídeos Iridoides , Iridoides/química , Iridoides/isolamento & purificação , Estrutura Molecular , Plantas Medicinais/química , Piranos/química , Piranos/isolamento & purificação
19.
Zhonghua Zhong Liu Za Zhi ; 27(1): 45-7, 2005 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-15771799

RESUMO

OBJECTIVE: To investigate the feasibility, reliability and therapeutic effectiveness of adjuvant chemotherapy for advanced hepatocellular carcinoma (HCC) after orthotopic liver transplantation (OLT). METHODS: The clinical data of adjuvant chemotherapy after OLT in 10 advanced HCC patients were studied retrospectively. FAP chemotherapy regimen was adopted calcium folinate (CF) 200 mg/m(2) and 5-Fluorouracil 500 mg/m(2) iv on D1 to D5, and doxorubicin 40 mg/m(2), cisplatin 30 mg/m(2) iv on D1, with 28 days as a cycle. The opportune time of chemotherapy, chemotherapy regimen, synergistic action between cytotoxic agent and immunosuppressive agent on liver and kidney and side-effects were preliminarily evaluated. RESULTS: 7/10 patients are surviving, with the longest survival of 32 months, and the shortest 9 months. Three patients died after operation, two at 13 months, one at 20 months after OLT, all died of metastasis. The incidence of one year survival was 9/9. During the period of chemotherapy, the side-effects of adjuvant chemotherapy were moderate. CONCLUSION: Chemotherapy which is able to prolong the life-span of patients with advanced HCC after orthotopic liver transplantation is feasible and effective, the side-effects were mild. The choice of opportune time of chemotherapy might influence the outcome.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Transplante de Fígado , Adulto , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , Doxorrubicina/administração & dosagem , Esquema de Medicação , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Humanos , Leucovorina/administração & dosagem , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Período Pós-Operatório , Estudos Retrospectivos , Taxa de Sobrevida
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