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1.
Kaohsiung J Med Sci ; 36(1): 43-53, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31642199

RESUMO

Accumulating evidences have proved the protective role of traditional Chinese medicine in improving neurological damage induced by cerebral hypoxia-ischemia. Herein, we hypothesized that Dendrobium officinale aqueous extract exerted neuroprotection against brain damage. Initially, a model of hypoxic-ischemic brain damage (HIBD) was induced in neonatal rats, which were subsequently intragastrically administered with different doses of Dendrobium officinale aqueous extract. Next, the antioxidant capacity was examined by enzyme-linked immunosorbent assay. 2,3,5-Triphenyltetrazolium chloride and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling staining assays were adopted to determine neuronal apoptosis in brain tissues. Furthermore, neurotrophic factors and hypoxia-inducible factor-1α (HIF-1α) expression was identified by Western blot analysis. The neonatal rat models of HIBD presented impaired neurobehaviors and antioxidant capacity, increased neuronal apoptosis and expression of HIF-1α and histone deacetylase 1 (HDAC1), as well as diminished expression of neurotrophic factors and K+ -Cl- -cotransporter 2 (KCC2). Notably, in response to different doses of Dendrobium officinale aqueous extract, the impairment on neurobehaviors and antioxidant capacity was alleviated, accompanied by reduced levels of nitric oxide synthase, nitric oxide, and malondialdehyde, and increased superoxide dismutase activity. Besides, the neuronal apoptosis was inhibited as reflected by down-regulated cleaved caspase-3 and Bax and up-regulated Bcl-2. Moreover, we also found accelerated expression of neurotrophic factors and KCC2 and diminished expression of HIF-1α and HDAC1. Altogether, this present study highlights that the aqueous extract of Dendrobium officinale can suppress the neuronal apoptosis and enhance the expression of neurotrophic factors to protect neonatal rats against HIBD.

2.
Biosci Biotechnol Biochem ; : 1-9, 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31791197

RESUMO

We investigated whether low-dose phloretin served as daily dietary supplements could ameliorate diabetic atherosclerosis and the role of kruppel-like factor 2 (KLF2). HUVECs cultured in high glucose medium were treated with different concentrations of phloretin and KLF2 mRNA, and protein level was detected. Diabetes was induced using streptozotocin in Apoe-/- mice after which they were fed a high-cholesterol diet for 8 weeks. Diabetic mice injected with KLF2 shRNA-lentivirus or control virus were treated with 20 mg/kg phloretin. Glucose, lipid profile, aortic atheroma, and endothelial nitric oxide synthase (eNOS) expression were detected. Phloretin retained endothelial function by KLF2-eNOS activation under hyperglycemia. Low-dose phloretin helped with lipid metabolism, and blocked the acceleration of atherosclerosis in STZ-induced diabetic mice since the early stage, which was diminished by KLF2 knockdown. Low-dose phloretin exhibited athero-protective effect in diabetic Apoe-/- mice dependent on KLF2 activation. This finding makes phloretin for diabetic atherosclerosis.

3.
Sci Rep ; 9(1): 18321, 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31797961

RESUMO

The novel methods for efficient plant regeneration via direct somatic embryogenesis (SE) and SE-mediated transformation system under high concentration of NAA in Ranunculus sceleratus were established. On MS media containing a high concentration of NAA (10.0 mg/L) in the dark, all inoculated explants (root, stem and leaf) formed somatic embryos at high frequencies, respectively, 66.03, 126.47 and 213.63 embryoids per explant, and 100% of the embryoids developed into plantlets on 1/2 MS rooting media. Morphological and histological analyses revealed that SE in R. sceleratus followed a classical pattern. All inoculated explants can be used as receptors for genetic transformation in R. sceleratus, through direct SE-mediated method after Agrobacterium infection. RcLEC1-B, as a marker gene, changed the number and morphology of flower organs and the development of cuticle in R. sceleratus, which indicated that the efficient transgenic system of R. sceleratus was established. To our knowledge, this is the first observation that both direct SE and transgenic transformation system, via induction of a single plant growth regulator, have been successfully constructed in R. sceleratus.

4.
Chin J Nat Med ; 17(12): 953-962, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31882051

RESUMO

Phytochemical investigation of the leaves and twigs of Callicarpa cathayana led to the isolation of six new clerodane diterpenoids, cathayanalactones A-F (1-6), together with seven analogues (7-13). Their structures were established by extensive NMR analyses together with experimental and calculated ECD spectra analyses. Compounds 1, 2, 3, 7 and 11 showed inhibitory activities on lipopolysaccharide-induced nitric oxide production in RAW264.7 cells.

5.
J Neuroinflammation ; 16(1): 282, 2019 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-31884963

RESUMO

BACKGROUND: Recent studies have demonstrated that natural killer (NK) cells can modulate other immune components and are involved in the development or progression of several autoimmune diseases. However, the roles and mechanisms of NK cells in regulating experimental autoimmune myasthenia gravis (EAMG) remained to be illustrated. METHODS: To address the function of NK cells in experimental autoimmune myasthenia gravis in vivo, EAMG rats were adoptively transferred with splenic NK cells. The serum antibodies, and splenic follicular helper T (Tfh) cells and germinal center B cells were determined by ELISA and flow cytometry. The roles of NK cells in regulating Tfh cells were further verified in vitro by co-culturing splenocytes or isolated T cells with NK cells. Moreover, the phenotype, localization, and function differences between different NK cell subtypes were determined by flow cytometry, immunofluorescence, and ex vivo co-culturation. RESULTS: In this study, we found that adoptive transfer of NK cells ameliorated EAMG symptoms by suppressing Tfh cells and germinal center B cells. Ex vivo studies indicated NK cells inhibited CD4+ T cells and Tfh cells by inducing the apoptosis of T cells. More importantly, NK cells could be divided into CXCR5- and CXCR5+ NK subtypes according to the expression of CXCR5 molecular. Compared with CXCR5- NK cells, which were mainly localized outside B cell zone, CXCR5+ NK were concentrated in the B cell zone and exhibited higher expression levels of IL-17 and ICOS, and lower expression level of CD27. Ex vivo studies indicated it was CXCR5- NK cells not CXCR5+ NK cells that suppressed CD4+ T cells and Tfh cells. Further analysis revealed that, compared with CXCR5- NK cells, CXCR5+ NK cells enhanced the ICOS expression of Tfh cells. CONCLUSIONS: These findings highlight the different roles of CXCR5- NK cells and CXCR5+ NK cells. It was CXCR5- NK cells but not CXCR5+ NK cells that suppressed Tfh cells and inhibited the autoimmune response in EAMG models.

6.
Crit Rev Eukaryot Gene Expr ; 29(2): 105-112, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31679265

RESUMO

OBJECTIVE: In this study, the molecular mechanism by which EPO regulates the angiogenesis after cerebral ischemia through AMPK-KLF2 signaling pathway was investigated. METHODS: Sixty healthy, male, C57BL/6 mice were randomly divided into three groups of 20 mice: a sham group, the middle cerebral artery occlusion (MCAO) group, and a MCAO+EPO treatment group. The MCAO model was established using a modified ZeaLonga method. Mice in the EPO treatment group were injected with EPO immediately after reperfusion (5000 IU/kg), and EPO was injected the following day. The number of mouse deaths and neurologic function scores were recorded during the experiment. On day 7 after cerebral ischemia, brain tissue proteins were extracted. The following proteins expressions were detected by western blot assay: EPO, vascular endothelial growth factor (VEGE), vascular endothelial growth factor receptor (KDR), adenosine activated protein kinase (AMPK), and alpha HIF-1α alpha (HIF-1α), KLF2 and nitric oxide synthase (eNOS). RESULTS: Compared with the MCAO group, the survival rate of mice in the EPO group was significantly improved and neurological function was significantly improved (P < 0.01). Western blot results showed that the content of EPO in brain tissue in MCAO group significantly increased compared with sham group. The content of EPO in the brain tissue of mice in the MCAO+EPO treatment group was significantly higher than in that of the MCAO group, which indicates that EPO increased the content of EPO in mouse brain tissue. Compared with the sham group, the protein expression of vascular endothelial growth factor (VEGE) and its receptor (KDR) in brain tissue of the MCAO group significantly decreased. However, the protein expression of VEGE and its receptor KDR in brain tissue of rats treated with MCAO+EPO was significantly higher than in that of the MCAO group. Thus, in this study, EPO was associated with vascular endothelial differentiation after cerebral ischemia in mice. The results of AMPK and KLF2 showed that the expression levels of AMPK and KLF2 in brain tissues of MCAO group mice significantly decreased compared with the sham group. However, the expression levels of AMPK and KLF2 in brain tissues of mice treated with MCAO+EPO were significantly higher than those in the MCAO group. Thus, EPO can activate AMPK and upregulate the expression of the transcription factor KLF2. The protein expression of HIF-1α in the brain tissue of mice in the MCAO group significantly increased compared with the sham group. However, the expression of HIF-1α in mice brain tissues in the MCAO+EPO treatment group was significantly lower than in that of the MCAO group, indicating that EPO was involved in regulating HIF-1α expression. The eNOS results showed that, compared with Sham group, the protein expression of eNOS in brain tissue of MCAO group mice significantly decreased. In the MCAO+EPO treatment group, the protein expression of eNOS was significantly higher in the brain tissue of the mice than in that of the MCAO group, indicating that EPO was involved in the synthesis of NO and promoted the angiogenesis. CONCLUSION: EPO promotes VEGE and its receptor (KDR) expression and participates in the regulation of HIF-1α and eNOS protein expression through the activation of AMPK-KLF2 signaling pathways to promote new vascular development after cerebral ischemia.

7.
J Neuroinflammation ; 16(1): 202, 2019 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-31679515

RESUMO

BACKGROUND: The thymus plays an essential role in the pathogenesis of myasthenia gravis (MG). In patients with MG, natural regulatory T cells (nTreg), a subpopulation of T cells that maintain tolerance to self-antigens, are severely impaired in the thymuses. In our previous study, upregulated nTreg cells were observed in the thymuses of rats in experimental autoimmune myasthenia gravis after treatment with exosomes derived from statin-modified dendritic cells (statin-Dex). METHODS: We evaluated the effects of exosomes on surface co-stimulation markers and Aire expression of different kinds of thymic stromal cells, including cTEC, mTEC, and tDCs, in EAMG rats. The isolated exosomes were examined by western blot and DLS. Immunofluorescence was used to track the exosomes in the thymus. Flow cytometry and western blot were used to analyze the expression of co-stimulatory molecules and Aire in vivo and in vitro. RESULTS: We confirmed the effects of statin-Dex in inducing Foxp3+ nTreg cells and found that both statin-Dex and DMSO-Dex could upregulate CD40 but only statin-Dex increased Aire expression in thymic stromal cells in vivo. Furthermore, we found that the role of statin-Dex and DMSO-Dex in the induction of Foxp3+ nTreg cells was dependent on epithelial cells in vitro. CONCLUSIONS: We demonstrated that statin-Dex increased expression of Aire in the thymus, which may further promote the Foxp3 expression in the thymus. These findings may provide a new strategy for the treatment of myasthenia gravis.

8.
Int J Biol Macromol ; 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31669658

RESUMO

In this study, four sequentially extracted polysaccharides (AEPs) from Amana edulis were modified by sulphation, phosphorylation, and carboxylation modifications (S-AEPs, P-AEPs, C-AEPs), and compared for their anti-oxidant activities. After modification, sugar and protein contents were decreased and uronic acid content was increased in comparison to native AEPs. UV absorption showed similar maximum absorption peaks of modified derivatives which indicated their homogeneous nature. FTIR spectra confirmed the conversion of hydroxyl groups to OS, COO, and POH bonds, respectively. The phosphorylated derivatives (P-AEPs) displayed the highest DPPH, hydroxyl radical, and ferrous ions radical scavenging abilities. Sulfated polysaccharides (S-AEPs) were observed with high reducing ability. The C-AEPs maintained the stable antioxidant properties after carboxylation modification. Our results indicated that the chemical modification of different polysaccharide components has significantly affected their antioxidant potential for their use in food industry and human health.

9.
Front Aging Neurosci ; 11: 235, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31619982

RESUMO

Normal aging is accompanied by hippocampus-dependent cognitive impairment, which is a risk factor of Alzheimer's disease. This study aims to investigate the effect of high frequency-repetitive transcranial magnetic stimulation (HF-rTMS) on hippocampus-dependent learning and memory in aged mice and explore its underlying mechanisms. Forty-five male Kunming mice (15 months old) were randomly divided into three groups: aged sham, 5 Hz rTMS, and 25 Hz rTMS. Two sessions of 5 Hz or 25 Hz rTMS comprising 1,000 pulses in 10 trains were delivered once a day for 14 consecutive days. The aged sham group was treated by the reverse side of the coil. In the adult sham group, 15 male Kunming mice (3 months old) were treated the same way as the aged sham group. A Morris water maze (MWM) was conducted following the stimulation, and synaptic ultrastructure was observed through a transmission electron microscope. HF-rTMS improved spatial learning and memory impairment in the aged mice, and 5 Hz was more significant than 25 Hz. Synaptic plasticity-associated gene profiles were modified by HF-rTMS, especially neurotrophin signaling pathways and cyclic adenosine monophosphate response element binding protein (CREB) cofactors. Compared to the aged sham group, synaptic plasticity-associated proteins, i.e., synaptophysin (SYN) and postsynaptic density (PSD)-95 were increased; brain-derived neurotrophic factor (BDNF) and phosphorylated CREB (pCREB) significantly increased after the 5 Hz HF-rTMS treatment. Collectively, our results suggest that HF-rTMS ameliorated cognitive deficits in naturally aged mice. The 5 Hz rTMS treatment significantly enhanced synaptic structural plasticity and activated the BDNF/CREB pathway in the hippocampus.

10.
Food Chem Toxicol ; 134: 110821, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31533060

RESUMO

The antifungal activity of plant essential oils (EOs) extracted by steam distillation from seven different species (Cinnamon, Anise, Clove, Citronella, Peppermint, Pepper, and Camphor) was investigated. Three common fungi were isolated from moldy wheat bread, which were identified as Aspergillus niger, A. oryzae, and A. ochraceus. The antifungal activity of anise, peppermint, clove, cinnamon, pepper, citronella, and camphor EOs from seven different spices was confirmed by agar diffusion assay against three fungi. Among all the EOs, the cinnamon EO showed the highest antifungal activity for all the fungi strains with the largest inhibition zone at the concentration of 800 mg/mL and lowest MIC ranging from 0.0625 to 0.125 mg/mL, followed by clove EO. The remaining EOs exerted moderate inhibitory effects. Further research indicated the substantial inhibitory activities of cinnamon and clove EOs on mycelial growth and spore germination in a dose-dependent manner. Further, the in vivo inhibitory activity of selected EOs on naturally infected bread demonstrated that cinnamon and clove EOs can as be used as natural antifungal agents.

11.
Cell Biol Int ; 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31498521

RESUMO

The progression of diabetic cardiomyopathy is related to cardiomyocyte dysfunction and apoptosis. Our previous studies showed that asporin (ASPN) was significantly increased in the myocardium of db/db mice through proteomics, and grape seed procyanidin B2 (GSPB2) significantly inhibited the expression of ASPN in the heart of db/db mice. We report here that ASPN played a critical role in glycated low-density lipoproteins (gly-LDL) induced-cardiomyocyte apoptosis. We found that gly-LDL upregulated ASPN expression. ASPN increased H9C2 cardiomyocyte apoptosis with down-regulation of Bcl-2, upregulation of transforming growth factor-ß1, Bax, collagen III, fibronectin, and phosphorylation of smad2 and smad3. However, GSPB2 treatment reversed ASPN-induced impairments in H9C2 cardiomyocytes. These results provide evidence for the cardioprotective action of GSPB2 against ASPN injury, and thus suggest a new target for fighting against diabetic cardiomyopathy.

12.
J Clin Pharm Ther ; 44(6): 858-867, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31436349

RESUMO

WHAT IS KNOWN AND OBJECTIVE: Statins are widely used worldwide in the prevention and treatment of coronary atherosclerotic heart disease and ischaemic stroke. However, in clinical application, statins have shown great individual differences in terms of the efficacy and safety, some of which are related to genetic factors. The purpose of this article was to summarize the recent advances about the correlation between gene polymorphisms and the efficacy/safety of statins. METHODS: We searched the databases including PharmGKB and PubMed (published before June 2019) using the keywords such as 'statin', 'gene polymorphism' and 'SNP' and obtained more than 100 articles. In this review, we described the clinical studies of genetic variants associated with both the efficacy and adverse reactions of statins. We also clarified the importance of taking pharmacogenetic variation into account to improve the clinical application of statins. RESULTS AND DISCUSSION: The available data were collected and analysed to present the polymorphisms of candidate genes encoding the most promising proteins including SLCO1B1 (encoding uptake transporters); ABCB1, ABCC2, ABCG2 (encoding effluent transporter); APOE, APOA5 (encoding apolipoprotein); genes encoding cytochrome P450 enzyme system; KIF6, HMGCR, LDLR, LPA, PCSK9, COQ2, CETP, etc These genes were proved to be related to the pharmacodynamics and pharmacokinetics of statins, thus affecting the efficacy and safety. WHAT IS NEW AND CONCLUSION: In this paper, the correlation between gene polymorphisms and the efficacy/safety of statins was summarized. The authors reached a consensus that the variants of the genes encoding uptake and effluent transporters have the most effect on the efficacy/safety of statins. It pointed out that it is desirable to do genetic testing of these transporter genes to reduce the incidence of myopathy or to achieve better outcomes before patients use statins, especially in the regions with high frequency of risk allele.

13.
Int J Biol Macromol ; 137: 160-168, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31255623

RESUMO

The rheological properties and emulsifying behavior of four polysaccharides (HBSS, CHSS, DASS, and CASS) sequentially extracted from Amana edulis (AEPs) were investigated under various concentrations, temperatures, pH levels, and ionic strengths. The apparent viscosity of the four AEPs solutions at 1% (w/w) concentration were found to be CHSS > DASS > HBSS > CASS. When the AEPs were heated to 100 οC, they showed lower colloidal viscosity, whereas after refrigeration and chilling, higher apparent viscosities were observed. The apparent viscosity of four AEPs at pH 10 or pH 4 was lower than that at pH 7. The apparent viscosity increased at a lower sodium ion concentration and then declined with an increase in ion concentration. The storage modulus (G') and loss modulus (G″) increased with an increase in oscillation frequency. The emulsifying activity and stability were enhanced as the concentration of the four AEPs increased. The emulsifying activity and stability of the AEPs were steady within the pH range of 2-10 and NaCl concentration range of 0-0.4 mol/L. Our results implied that these polysaccharides can be utilized as a novel hydrocolloid source for natural thickeners in the food industry.


Assuntos
Liliaceae/química , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Reologia , Cálcio/química , Emulsões , Indústria Alimentícia , Concentração de Íons de Hidrogênio , Temperatura Ambiente , Viscosidade
14.
J Neuroinflammation ; 16(1): 119, 2019 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-31171009

RESUMO

After the publication of the original article [1], it came to the authors' attention that there was an error in the originally published version of Fig. 5b. The image of CD4+CD25+ T cells of the statin-Dex group was unintentionally replaced with the image of CD4+CD25+ T cells from the control group. The correct version of Fig. 5b is published in this Erratum.

15.
CNS Neurosci Ther ; 25(11): 1254-1261, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31228356

RESUMO

BACKGROUND: Autism spectrum disorder (ASD) is a very complex neurodevelopmental disorder, characterized by social difficulties and stereotypical or repetitive behavior. Some previous studies using low-frequency repetitive transcranial magnetic stimulation (rTMS) have proven of benefit in ASD children. METHODS: In this study, 32 children (26 males and six females) with low-function autism were enrolled, 16 children (three females and 13 males; mean ± SD age: 7.8 ± 2.1 years) received rTMS treatment twice every week, while the remaining 16 children (three females and 13 males; mean ± SD age: 7.2 ± 1.6 years) served as waitlist group. This study investigated the effects of rTMS on brain activity and behavioral response in the autistic children. RESULTS: Peak alpha frequency (PAF) is an electroencephalographic measure of cognitive preparedness and might be a neural marker of cognitive function for the autism. Coherence is one way to assess the brain functional connectivity of ASD children, which has proven abnormal in previous studies. The results showed significant increases in the PAF at the frontal region, the left temporal region, the right temporal region and the occipital region and a significant increase of alpha coherence between the central region and the right temporal region. Autism Behavior Checklist (ABC) scores were also compared before and after receiving rTMS with positive effects shown on behavior. CONCLUSION: These findings supported our hypothesis by demonstration of positive effects of combined rTMS neurotherapy in active treatment group as compared to the waitlist group, as the rTMS group showed significant improvements in behavioral and functional outcomes as compared to the waitlist group.

16.
Proc Natl Acad Sci U S A ; 116(20): 9820-9824, 2019 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-31036653

RESUMO

Middle to Late Pleistocene human evolution in East Asia has remained controversial regarding the extent of morphological continuity through archaic humans and to modern humans. Newly found ∼300,000-y-old human remains from Hualongdong (HLD), China, including a largely complete skull (HLD 6), share East Asian Middle Pleistocene (MPl) human traits of a low vault with a frontal keel (but no parietal sagittal keel or angular torus), a low and wide nasal aperture, a pronounced supraorbital torus (especially medially), a nonlevel nasal floor, and small or absent third molars. It lacks a malar incisure but has a large superior medial pterygoid tubercle. HLD 6 also exhibits a relatively flat superior face, a more vertical mandibular symphysis, a pronounced mental trigone, and simple occlusal morphology, foreshadowing modern human morphology. The HLD human fossils thus variably resemble other later MPl East Asian remains, but add to the overall variation in the sample. Their configurations, with those of other Middle and early Late Pleistocene East Asian remains, support archaic human regional continuity and provide a background to the subsequent archaic-to-modern human transition in the region.

17.
Am J Perinatol ; 2019 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-31013539

RESUMO

OBJECTIVE: To explore the clinical significance of early premature infant oral motor intervention (PIOMI) in the prognosis of premature infants. STUDY DESIGN: Infants were randomly divided into an intervention group (n = 78) and a control group (n = 73). PIOMI was given to the intervention group 15 to 30 minutes before feeding once a day for 14 days. The whole procedure lasted 15 minutes, including oral stimulation and nonnutritive sucking. Oral feeding ability and neuromotor development were evaluated using the Preterm Infant Oral Feeding Readiness Assessment (PIOFRA) scale and Infant Neurological International Battery (Infanib) scale. RESULTS: The PIOFRA score was higher in the intervention group and increased with time, showing a group-time interaction effect. The intervention group exhibited a higher feeding efficiency, a shorter transition time from assisted oral feeding to independent oral feeding, and lower body weight at achievement of independent oral feeding. The percentages of infants with a normal score on the Infanib scale were higher in the intervention group at 3 and 6 months of age, and an abnormal ratio was lower in the intervention group at 6 months (p < 0.01). CONCLUSION: PIOMI promoted neuromotor coordination by improving neurodevelopment, thereby improving the oral feeding ability and prognosis of preterm infants.

19.
Pharm Biol ; 57(1): 226-230, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30946631

RESUMO

CONTEXT: We identified an active prenylated derivative of genistein, 8-prenylgenistein (8PG) from Erythrina variegata L. (Leguminosae) and found that 8PG increased osteoprotective effects of genistein in oestrogen-deficient mice. OBJECTIVE: This study investigated and compared the oestrogenic effects of genistein and 8PG on uterus and vagina of immature mice. MATERIALS AND METHODS: Immature female CD-1 mice were orally treated with vehicle (Control, n = 10) or genistein (75 mg/kg, n = 10) or 8PG with low (8PG-L, 75 mg/kg, n = 10) and high dose (8PG-H, 150 mg/kg, n = 10) for 7 consecutive days by intragastric gavage. The uterus and vagina were harvested for histological and molecular measurements. RESULTS: Treatment with genistein and 8PG-H significantly increased uterus index (1.98 ± 0.21 & 1.49 ± 0.16 mg/g) and vagina index (3.83 ± 0.11 & 3.13 ± 0.25 mg/g) as compared to untreated control (uterus, 1.12 ± 0.13 mg/g; vagina, 2.32 ± 0.18 mg/g). Accordingly, both genistein and 8PG-H made vaginal cells keratinized and induced uterine and vaginal hypertrophy associated with the endometrial proliferation. 8PG-L did not affect oestrus cycle and histology of uterus and vagina. Treatment of immature mice with genistein or 8PG-H upregulated protein expression of oestrogen receptor-α (ER-α) and proliferating cell nuclear antigen (PCNA), but 8PG-L did not alter ER-α and PCNA expression in uterus and vagina. CONCLUSION: This study indicated that 8-prenylgenistein exerted oestrogenic effects in immature female mice. The efficacy and safety of 8-prenylgenistein when applied in improving oestrogen deficiency-induced syndrome requires further elucidation.


Assuntos
Estrogênios/farmacologia , Genisteína/análogos & derivados , Genisteína/farmacocinética , Útero/efeitos dos fármacos , Vagina/efeitos dos fármacos , Administração Oral , Animais , Relação Dose-Resposta a Droga , Receptor alfa de Estrogênio/metabolismo , Estrogênios/administração & dosagem , Estrogênios/toxicidade , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Genisteína/administração & dosagem , Genisteína/farmacologia , Genisteína/toxicidade , Camundongos , Regulação para Cima/efeitos dos fármacos , Útero/metabolismo , Vagina/metabolismo
20.
Front Genet ; 10: 123, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30873207

RESUMO

Atherosclerosis is one of the most common type of cardiovascular disease and the prime cause of mortality in the aging population worldwide. However, the detail mechanisms and special biomarkers of atherosclerosis remain to be further investigated. Lately, long non-coding RNAs (lncRNAs) has attracted much more attention than other types of ncRNAs. In our work, we found and confirmed differently expressed lncRNAs and mRNAs in atherosclerosis by analyzing GSE28829. We performed the weighted gene co-expression network analysis (WGCNA) by analyzing GSE40231 to confirm highly correlated genes. Gene Ontology (GO) analysis were utilized to assess the potential functions of differential expressed lncRNAs in atherosclerosis. Co-expression networks were also constructed to confirm hub lncRNAs in atherosclerosis. A total of 5784 mRNAs and 654 lncRNAs were found to be dysregulated in the progression of atherosclerosis. A total of 15 lncRNA-mRNA co-expression modules were identified in this study based on WGCNA analysis. Moreover, a few lncRNAs, such as ZFAS1, LOC100506730, LOC100506691, DOCK9-AS2, RP11-6I2.3, LOC100130219, were confirmed as important lncRNAs in atherosclerosis. Taken together, bioinformatics analysis revealed these lncRNAs were involved in regulating the leukotriene biosynthetic process, gene expression, actin filament organization, t-circle formation, antigen processing, and presentation, interferon-gamma-mediated signaling pathway, and activation of GTPase activity. We believed that this study would provide potential novel therapeutic and prognostic targets for atherosclerosis.

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