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In this study, switchable terahertz (THz) multi-orbital angular momentum (OAM) Bessel beams (BBs) were developed based on a spin-decoupled reflective multifunctional metasurface (MTS). Switchability was achieved by switching the feed between left-hand circular polarization (LCP), right-hand circular polarization (RCP), and linear polarization (LP) incidences. A switchable physical model was established for calculating the beam direction, OAM mode, polarization, and non-diffractive distance of the outgoing BBs. As an example, a spin-decoupled MTS was designed to generate dual BBs under LCP incidence, which was subsequently switched to RCP or LP for switchability. The outgoing BBs could be switched among three types of beams: Type-1 under LCP incidence (LCP, θL = 40°, φL = 0°, lL = 1, dL = 18â cm) and (RCP, θR = -40°, φR = 0°, lR = -1, dR = 20â cm); Type-2 under RCP incidence (RCP, θR = 40°, φR = 0°, lR = 1, dR = 18â cm) and (LCP, θL = -19°, φL = 0°, lL = 3, dL = 16.4â cm); and Type-3 under LP incidence (LP, θ = 40°, φ = 0°, l = 1, d = 18â cm), (RCP, θR = -40°, φR = 0°, lR = -1, dR = 20â cm) and (LCP, θL = -19°, φL = 0°, lL = 3, dL = 16.4â cm). Compared with previous MTSs, the proposed spin-decoupled MTS has the advantages of switchability among BBs, high non-diffractive distance/aperture size ratio of 15, large beam deflection angle of up to 40°, and high BB conversion efficiency of up to 96%. The simulated results were consistent with those calculated using the physical model, thus validating the physical model. The designed switchable BBs have potential THz near-field applications, such as high-capacity near-field wireless communications, wireless power transfer, high-resolution imaging, non-destructive testing, and speed detection of high-speed rotating objects.
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This Letter develops a spin-decoupled reconfigurable reflective orbital angular momentum (OAM) metasurface (MTS). The reconfigurability is realized by switching the feed among left-hand circular polarization (LHCP), right-hand circular polarization (RHCP), and linear polarization (LP) incidences, and the reconfigurable design principle is provided. This Letter also proposes a design method for the desired energy ratio between the co-polarized and cross-polarized beams. Compared with published multifunction MTSs, the designed MTSs have the following advantages: multi-polarizations, arbitrary beam numbers and modes, composite waveform (pencil and OAM beams), high aperture efficiency (21.1%, 14.6%, 6.63% for RHCP, LP, and LHCP incidences, respectively), high purity (above 92.41%), required energy distribution ratio, and reconfigurability. The MTSs have potential prospects in high-capacity wireless communications.
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This Letter presents a single-layer, dual-frequency unit for generating orbital angular momentum (OAM) in the microwave range. The unit cell consists of a square frame and two concentric rings with branches. The developed units can produce multifunctional OAM with required OAM mode, beam number, and direction. To demonstrate this versatility, three reflectarrays operating at dual frequencies are designed, and one is fabricated and measured to validate the design. The reflectarray has the following advantages: high gain (15.4dBi at 10 GHz, 20.3dBi at 20 GHz), high aperture efficiency (13.53% at 10 GHz, 10.33% at 20 GHz), low divergence angle (7.5°at 10 GHz, 6° at 20 GHz), small size, and compactness in the form of a single-layer structure. The designed multifunctional reflectarray has potential applications in remote sensing, point-to-point communication, satellite communications, and others.
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BACKGROUND: Zuo-Jin-Wan (ZJW), a two-herb formula consisting of Coptis chinensis (CC) and Evodia rutaecarpa (ER), is commonly used in traditional Chinese medicine for the treatment of cancers. However, the efficacies and mechanisms of ZJW and its alkaloid components on cancers are still unclear. METHODS: Here we investigated the anti-cancer effects and mechanisms of ZJW, CC, ER, berberine, and evodiamine in cells and in intrahepatic xenograft mice. RESULTS: Treatment of HepG2 cells with ZJW, CC, ER, berberine, and evodiamine significantly displayed cytotoxic effects in a dose- and time-dependent manner. Hierarchical cluster analysis of gene expression profiles showed that CC and ZJW shared a similar mechanism for the cytotoxic effects, suggesting that CC was the active ingredient of ZJW for anti-cancer activity. Network analysis further showed that c-myc was the likely key molecule involved in the regulation of ZJW-affected gene expression. A human hepatoma xenograft model was established by intrahepatic injection of HepG2 cells containing nuclear factor-κB-driven luciferase genes in immunocompetent mice. In vivo bioluminescence imaging showed that cells had been successfully transplanted in mouse liver. Oral administration of ZJW for 28 consecutive days led to a significant decrease in the accumulation of ascites, the ratio of tumor-to-liver, and the number of transplanted cells in livers. CONCLUSIONS: In conclusion, our findings suggested for the first time that ZJW significantly suppressed human cancer cell growth in orthotopic HepG2 xenograft-bearing immunocompetent mice. Moreover, c-myc might play a potent role in the cytotoxic mechanisms of ZJW, CC, ER, berberine, and evodiamine.
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Alcaloides/farmacologia , Berberina/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Coptis/química , Medicamentos de Ervas Chinesas/farmacologia , Evodia/química , Quinazolinas/farmacologia , Alcaloides/uso terapêutico , Animais , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/uso terapêutico , Berberina/uso terapêutico , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/uso terapêutico , Feminino , Células Hep G2 , Xenoenxertos , Humanos , Medicina Tradicional Chinesa , Camundongos Endogâmicos ICR , Fitoterapia , Quinazolinas/uso terapêuticoRESUMO
Safrole oxide (SAFO), a metabolite of naturally occurring hepatocarcinogen safrole, is implicated in causing DNA adduct formation. Our previous study first detected the most abundant SAFO-induced DNA adduct, N7-(3-benzo[1,3] dioxol-5-yl-2-hydroxypropyl)guanine (N7γ-SAFO-G), in mouse urine using a well-developed isotope-dilution high-performance liquid chromatography-electrospray ionization tandem mass spectrometry (ID-HPLC-ESI-MS/MS) method. This study further elucidated the genotoxic mode of action of SAFO in mice treated with SAFO 30, 60, 90, or 120 mg/kg for 28 days. The ID-HPLC-ESI-MS/MS method detected N7γ-SAFO-G with excellent sensitivity and specificity in mouse liver and urine of SAFO-treated mice. Our data provide the first direct evidence of SAFO-DNA adduct formation in rodent tissues. N7γ-SAFO-G levels in liver were significantly increased by SAFO 120 mg/kg compared with SAFO 30 mg/kg, suggesting rapid spontaneous or enzymatic depurination of N7γ-SAFO-G in tissue DNA. Urinary N7γ-SAFO-G exhibited a sublinear dose response. Moreover, the micronucleated peripheral reticulocyte frequencies increased dose-dependently and significantly correlated with N7γ-SAFO-G levels in liver (r = 0.8647; p < 0.0001) and urine (r = 0.846; p < 0.0001). Our study suggests that safrole-mediated genotoxicity may be caused partly by its metabolic activation to SAFO and that urinary N7γ-SAFO-G may serve as a chemically-specific cancer risk biomarker for safrole exposure.
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Adutos de DNA , Safrol , Camundongos , Animais , Safrol/toxicidade , Espectrometria de Massas em Tandem , Espectrometria de Massas por Ionização por Electrospray/métodos , Guanina , Reticulócitos/química , Reticulócitos/metabolismo , Fígado/metabolismo , Cromatografia Líquida de Alta PressãoRESUMO
Aristolochic acids (AAs) are naturally occurring genotoxic carcinogens linked to Balkan endemic nephropathy and aristolochic acid nephropathy. Aristolochic acid I and II (AA-I and AA-II) are the most abundant AAs, and AA-I has been reported to be more genotoxic and nephrotoxic than AA-II. This study aimed to explore metabolic differences underlying the differential toxicity. We developed a novel microdialysis sampling coupled with solid-phase extraction liquid chromatography-tandem mass spectrometry (MD-SPE-LC-MS/MS) to simultaneously study the toxicokinetics (TK) of AA-I and AA-II and their corresponding aristolactams (AL-I and AL-II) in the blood of Sprague Dawley rats co-treated with AA-1 and AA-II. Near real-time monitoring of these analytes in the blood of treated rats revealed that AA-I was absorbed, distributed, and eliminated more rapidly than AA-II. Moreover, the metabolism efficiency of AA-I to AL-I was higher compared to AA-II to AL-II. Only 0.58% of AA-I and 0.084% of AA-II was reduced to AL-I and AL-II, respectively. The findings are consistent with previous studies and support the contention that differences in the in vivo metabolism of AA-I and AA-II may be critical factors for their differential toxicities.
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Ácidos Aristolóquicos , Nefropatia dos Bálcãs , Nefropatias , Ratos , Animais , Cromatografia Líquida/métodos , Ácidos Aristolóquicos/toxicidade , Ácidos Aristolóquicos/química , Espectrometria de Massas em Tandem/métodos , Ratos Sprague-Dawley , Microdiálise , ToxicocinéticaRESUMO
INTRODUCTION: Rs9296559 within CD2-associated protein (CD2AP) has been identified as a susceptibility locus for Alzheimer's disease (AD). Recent studies indicated that CD2AP functioned as a regulator of endocytic trafficking to modulate the ß-amyloid (Aß) generation in neurons. Moreover, knockdown of cindr, the Drosophila ortholog of CD2AP, enhanced tau-induced neurodegeneration, implying CD2AP also participated in tau pathology. However, the role of rs9296559 in regulating Aß and tau metabolism in AD was still unclear. METHODS: Here, the associations of rs9296559 with CSF Aß1-42, p-tau, and t-tau were performed using a linear regression model in a total of 543 cognitive normal (CN), mild cognitive impairment (MCI), and AD subjects from the Alzheimer's disease Neuroimaging Initiative (ADNI) cohort. The results were replicated in an independent cohort consisting of 198 Chinese subjects recruited from our hospital. RESULTS: In the ADNI cohort, CC + TC genotypes significantly increased CSF t-tau and p-tau levels in MCI patients but did not alter CSF tau levels in AD. This association was also observed in the replication cohort. Moreover, there was no association between rs9296559 and CSF Aß1-42 level at different disease statuses in the two cohorts. CONCLUSION: Our findings showed that rs9296559 was associated with higher CSF t-tau and p-tau levels in MCI, supporting that CD2AP modified AD risk by altering tau-related neurodegeneration in the early stage of the AD continuum. To the best of our knowledge, this is the first study to evaluate the association between CD2AP genotypes and AD CSF biomarkers.
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Proteínas Adaptadoras de Transdução de Sinal/genética , Doença de Alzheimer/genética , Disfunção Cognitiva/genética , Proteínas do Citoesqueleto/genética , Polimorfismo de Nucleotídeo Único , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/líquido cefalorraquidiano , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Disfunção Cognitiva/líquido cefalorraquidiano , Feminino , Humanos , Masculino , Fragmentos de Peptídeos/líquido cefalorraquidiano , Proteínas tau/líquido cefalorraquidianoRESUMO
Introduction: Diabetes mellitus (DM) is a pathological hyperglycemic state related to the dysregulation of insulin. Chronic kidney disease (CKD) is a common chronic complication in diabetic patients. A vegetarian diet could be one of the preventive strategies for the occurrence of CKD in patients with diabetes mellitus. However, it is still unknown whether a vegetarian diet lowers the occurrence of CKD in DM patients. Research Design and Methods: This retrospective study was conducted at Taipei Tzu Chi Hospital from 5 September 2005 to 31 December 2016. Subjects with an HbA1c level > 6.5% or previous history of diabetes mellitus elder than 40 years were grouped based on self-reported dietary habits (vegetarians, lacto-ovo vegetarians and omnivores) in the structured questionnaire. Structural equation modeling (SEM) was applied to estimate the direct and indirect effects of variables on the occurrence of chronic kidney disease. Results: Among these 2,797 subjects, the participants were grouped into dietary habits as vegans (n = 207), lacto-ovo vegetarians (n = 941) and omnivores (n = 1,649). The incidence of overall CKD was higher in the omnivore group [36.6% vs 30.4% (vegans) and 28.5% (lacto-ovo vegetarian), p < 0.001]. In the SEM model, after adjusting for age and sex, the lacto-ovo vegetarian [OR: 0.68, 95% confidence interval (CI): 0.57-0.82] and vegan groups (OR 0.68, 95% CI: 0.49-0.94) were both associated with a lower risk of CKD occurrence than the omnivore group. The vegan diet and lacto-ovo diet lowered the risk related to a high BMI (OR: 0.45, p < 0.001, OR: 0.58, p < 0.001) and hyperuricemia (OR: 0.53, p < 0.001; OR: 0.55, p < 0.001) for the occurrence of CKD. Conclusion: Vegetarian dietary habits were associated with a lower occurrence of CKD in DM patients.
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Obesity is a prevalent metabolic disease that increases the risk of other diseases, such as hypertension, diabetes, hyperlipidemia, cardiovascular disease, and certain cancers. A meta-analysis of 11 randomized sham-controlled trials indicates that acupuncture had adjuvant benefits in improving simple obesity, and previous studies have reported that acupoint combinations were more useful than single-acupoint therapy. The Apriori algorithm, a data mining-based analysis that finds potential correlations in datasets, is broadly applied in medicine and business. This study, based on the Apriori algorithm-based association rule analysis, found the association rules of acupoints among 11 randomized controlled trials (RCTs). There were 23 acupoints extracted from 11 RCTs. We used Python to calculate the association between acupoints and disease. We found the top 10 frequency acupoints were Extra12, TF4, LI4, LI11, ST25, ST36, ST44, CO4, CO18, and CO1. We investigated the 1118 association rule and found that {LI4, ST36} ≥ {ST44}, {LI4, ST44} ≥ {ST36}, and {ST36, ST44} ≥ {LI4} were the most associated rules in the data. Acupoints, including LI4, ST36, and ST44, are the core acupoint combinations in the treatment of simple obesity.
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Background: Stroke leads to tremendous impacts on patients and the healthcare system. It is crucial to explore the potential management of rehabilitation. Acupuncture and traditional Chinese herbal medicine (TCHM) integrated with conventional rehabilitation benefit post-stroke functional recovery. Methods: We retrospectively reviewed the medical records of all patients included in the Integrated Traditional Chinese-Western Medicine care program for stroke (ITCWM-stroke care program) in 2019 in Taipei Tzu Chi Hospital to investigate the effects of acupuncture and TCHM integrated with conventional rehabilitation on National Institutes of Health Stroke Scale (NIHSS) and Barthel Index (BI) scores before and after the program. Results: A total of 255 stroke inpatients were retrieved and divided into acupuncture and acupuncture + TCHM group by hemorrhagic and ischemic stroke types, respectively. All the patients were recruited in the program at the early subacute phase after stroke onset. Of the hemorrhagic and ischemic stroke subjects, the NIHSS and BI total scores were significantly improved in the acupuncture and acupuncture + TCHM groups. The subgroup analysis results showed that in subjects with a baseline BI score ≤ 40, the acupuncture + TCHM group significantly improved BI total score better than the acupuncture group in both hemorrhagic (p < 0.05) and ischemic (p < 0.05) stroke subjects. Conclusion: Acupuncture and TCHM integrated with conventional rehabilitation significantly improve stroke patients' functional recovery at the early subacute phase. Acupuncture + TCHM contributes to better activities of daily living (ADL) improvements in stroke patients with a baseline BI score ≤ 40. We suggest integrating acupuncture and TCHM into the post-stroke rehabilitation strategy, especially for stroke patients with poor ADL function.
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Safrole-2',3'-oxide (SAFO) is a reactive electrophilic metabolite of the hepatocarcinogen safrole, the main component of sassafras oil. Safrole occurs naturally in a variety of spices and herbs, including the commonly used Chinese medicine Xi xin (Asari Radix et Rhizoma) and Dong quai (Angelica sinensis). SAFO is the most mutagenic metabolite of safrole tested in the Ames test. However, little or no data are available on the genotoxicity of SAFO in mammalian systems. In this study, we investigated the cytotoxicity and genotoxicity of SAFO in human HepG2 cells and male FVB mice. Using MTT assay, SAFO exhibited a dose- and time-dependent cytotoxic effect in HepG2 cells with TC(50) values of 361.9µM and 193.2µM after 24 and 48h exposure, respectively. In addition, treatment with SAFO at doses of 125µM and higher for 24h in HepG2 cells resulted in a 5.1-79.6-fold increase in mean Comet tail moment by the alkaline Comet assay and a 2.6-7.8-fold increase in the frequency of micronucleated binucleated cells by the cytokinesis-block micronucleus assay. Furthermore, repeated intraperitoneal administration of SAFO (15, 30, 45, and 60mg/kg) to mice every other day for a total of twelve doses caused a significant dose-dependent increase in mean Comet tail moment in peripheral blood leukocytes (13.3-43.4-fold) and in the frequency of micronucleated reticulocytes (1.5-5.8-fold). Repeated administration of SAFO (60mg/kg) to mice caused liver lesions manifested as a rim of ballooning degeneration of hepatocytes immediately surrounding the central vein. Our data clearly demonstrate that SAFO significantly induced cytotoxicity, DNA strand breaks, micronuclei formation both in human cells in vitro and in mice. More studies are needed to explore the role SAFO plays in safrole-induced genotoxicity.
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Dano ao DNA , Mutagênicos/toxicidade , Safrol/análogos & derivados , Safrol/toxicidade , Animais , Ensaio Cometa , Células Hep G2 , Humanos , Leucócitos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos , Testes para MicronúcleosRESUMO
In dealing with the complex issues of greenhouse gas (GHG) emission and climate change mitigation, many interrelated factors such as cost, level of technology development, supply and demand of energy, structure of industry, and expenditures on research and development exist. Using indicators to monitor environmental impacts and evaluate the efficacies of policies and regulations has been practiced for a long time, and it can serve as a useful tool for decision making and for comparison between different countries. Although numerous indicators have been developed for relevant subjects, integrated approaches that consider individual changes, dynamic interaction, and multi-dimensions of indicators are scarce. This paper aimed to develop a Driving Force-Pressure-State-Impact-Response (DPSIR) framework to assess the problems. This DPSIR model is mainly related to energy consumption, environmental impacts, and policy responses. The objectives of the paper were: (1) conduct a literature review on the indicators that have been used in GHG-related studies; (2) develop a DPSIR model that incorporates GHG-related indicators and evaluate their relationships using a cause-effect chain of GHG emission; and (3) develop a calculative method that can be used to explain the dynamic correlation among the interdependent indicators. Taiwan is a significant source of global GHG emissions. A case study, using the developed framework and Taiwan's actual data of the past two decades, was conducted. The results indicate that regulatory strategies for pollution control are inadequate in terms of ensuring environmental quality, and the nature does not have the capability to revert the impacts from the existing level of pollution.
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Poluentes Atmosféricos/análise , Efeito Estufa , Modelos Químicos , Poluição do Ar/estatística & dados numéricos , Técnicas de Apoio para a Decisão , TaiwanRESUMO
OBJECTIVE: To investigate the effects of anluohuaqianwan on experimental hepatic fibrosis induced by dimethyl nitrosamine (DMN) in rats. METHODS: 36 male SD rats were randomly dividied into three groups: model group, normal group, anluohuaqianwan group. The rats in the three groups were treated with DMN daily for 4 weeks. The liver function was detected using auto biochemistry analyzer, the serum HA, LN, IV-C, PIIIP were detected by immunoradiometry, the histopathology was observed in the left liver lobe after HE staining, the expression of matrix metalloproteinase-2 (MMP-2) in liver tissue were detected by immunohistochemistry. RESULTS: The serum levels of ALT, AST, ALP, TP, ALB and the contents of HA, LN, IV-C in model group were significantly increased compared to these in the normal group (P less than 0.01). The serum levels of ALT, AST and the contents of HA in anluohuaqianwan group were significantly lower than those in the model group (P less than 0.01). The liver MMP-2 in the model group was significantly increased compared to that in the normal group (P less than 0.05). The expression of MMP-2 in liver tissue of model group was lower than that in the anluohuaqianwan group (P less than 0.05). CONCLUSION: Anluohuaqianwan can inhibit liver fibrosis in rats induced by DMN.
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Medicamentos de Ervas Chinesas/farmacologia , Ácido Hialurônico/sangue , Cirrose Hepática Experimental/tratamento farmacológico , Fígado/efeitos dos fármacos , Metaloproteinase 2 da Matriz/metabolismo , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Dimetilnitrosamina , Combinação de Medicamentos , Medicamentos de Ervas Chinesas/uso terapêutico , Hidroxiprolina/metabolismo , Imuno-Histoquímica , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática Experimental/induzido quimicamente , Cirrose Hepática Experimental/metabolismo , Cirrose Hepática Experimental/patologia , Testes de Função Hepática , Masculino , Plantas Medicinais/química , Distribuição Aleatória , Ratos , Ratos Sprague-DawleyRESUMO
Asatone is an active component extracted from the Chinese herb Radix et Rhizoma Asari. Our preliminary studies have indicated that asatone has an anti-inflammatory effect on RAW 264.7 culture cells challenged with lipopolysaccharide (LPS). Acute lung injury (ALI) has high morbidity and mortality rates due to the onset of serious lung inflammation and edema. Whether asatone prevents ALI LPS-induced requires further investigation. In vitro studies revealed that asatone at concentrations of 2.5-20[Formula: see text][Formula: see text]g/mL drastically prevented cytotoxicity and concentration-dependently reduced NO production in the LPS-challenged macrophages. In an in vivo study, the intratracheal administration of LPS increased the lung wet/dry ratio, myeloperoxidase activity, total cell counts, white blood cell counts, NO, iNOS, COX, TNF-[Formula: see text], IL-1[Formula: see text], and IL-6 in the bronchoalveolar lavage fluid as well as mitogen-activated protein kinases in the lung tissues. Pretreatment with asatone could reverse all of these effects. Asatone markedly reduced the levels of TNF-[Formula: see text] and IL-6 in the lung and liver, but not in the kidney of mice. By contrast, LPS reduced anti-oxidative enzymes and inhibited NF-[Formula: see text]B activations, whereas asatone increased anti-oxidative enzymes in the bronchoalveolar lavage fluid and NF-[Formula: see text]B activations in the lung tissues. Conclusively, asatone can prevent ALI through various anti-inflammatory modalities, including the major anti-inflammatory pathways of NF-[Formula: see text]B and mitogen-activated protein kinases. These findings suggest that asatone can be applied in the treatment of ALI.
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Lesão Pulmonar Aguda/genética , Lesão Pulmonar Aguda/prevenção & controle , Asarum/química , Mediadores da Inflamação/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Fitoterapia , Extratos Vegetais/administração & dosagem , Extratos Vegetais/farmacologia , Lesão Pulmonar Aguda/induzido quimicamente , Animais , Anti-Inflamatórios , Citocinas/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Lipopolissacarídeos/efeitos adversos , Macrófagos/metabolismo , Masculino , Camundongos , Óxido Nítrico/metabolismo , Células RAW 264.7RESUMO
Chronic cerebral hypoperfusion has been associated with cognitive impairment in dementias, such as Alzheimer's disease (AD) and vascular disease (VaD), the two most common neurodegenerative diseases in aged people. However, the effective therapeutic approaches for both AD and VaD are still missing. MicroRNAs (miRNAs) are small non-coding RNAs that play important roles in the epigenetic regulation in many neurological disorders; the critical roles of miRNAderegulation had been implicated in both AD and VaD. In the current study, we reported that miR-9-5p is elevated in the serum and cerebrospinalfluid of patientswith VaD. The miR-9-5p wasalso increased in both the hippocampus and cortex of rats with 2-vessel occlusionsurgery. Furthermore, application ofmiR-9-5p antagomirs attenuated the memory impairments in rats with 2-vessel occlusion surgery both in the Morris water maze and inhibitory avoidance step-down tasks. Furthermore, miR-9-5p antagomirs reducedthe inhibition oflong-term potentiation and loss of dendritic spines in chronic cerebral hypoperfusionrats. Additionally, the cholinergic neuronal function was rescued by miR-9-5p antagomirs, as well as the neuronal loss and the oxidative stress. We concluded that miR-9-5p inhibition may be a potential therapeutic target for the memory impairments caused by chronic cerebral hypoperfusion.
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BACKGROUND: Abnormal activation of PI3K/AKT/mTOR (PAM) pathway, caused by PIK3CA mutation, KRAS mutation, PTEN loss, or AKT1 mutation, is one of the most frequent signaling abnormalities in breast carcinoma. However, distribution and frequencies of mutations in PAM pathway are unclear in breast cancer patients from the mainland of China and the correlation between these mutations and breast cancer outcome remains to be identified. METHODS: A total of 288 patients with invasive ductal breast cancer were recruited in this study. Mutations in PIK3CA (exons 4, 9 and 20), KRAS (exon 2) and AKT1 (exon 3) were detected using Sanger sequencing. PTEN loss was measured by immunohistochemistry assay. Correlations between these genetic aberrations and clinicopathological features were analyzed. RESULTS: The frequencies of PIK3CA mutation, KRAS mutation, AKT1 mutation and PTEN loss were 15.6%, 1.8%, 4.4% and 35.3%, respectively. However, except for PTEN loss, which was tied to estrogen receptor (ER) status, these alterations were not associated with other clinicopathological features. Survival analysis demonstrated that PIK3CA mutation, PTEN loss and PAM pathway activation were not associated with disease-free survival (DFS). Subgroup analysis of patients with ER positive tumors revealed that PIK3CA mutation more strongly reduced DFS compared to wild-type PIK3CA (76.2% vs. 54.2%; P = 0.011). PIK3CA mutation was also an independent factor for bad prognosis in ER positive patients. CONCLUSIONS: AKT1, KRAS and PIK3CA mutations and PTEN loss all exist in women with breast cancer in the mainland China. PIK3CA mutation may contribute to the poor outcome of ER positive breast carcinomas, providing evidence for the combination of PI3K/AKT/mTOR inhibitors and endocrine therapy.