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Backgrounds: Advanced ovarian cancer is frequently accompanied by extensive peritoneal metastasis, complicating surgical interventions. This study aims to explore the application of 3D reconstruction and 3D printing technology in the treatment of advanced ovarian cancer. Methods: We conducted a retrospective analysis of 60 patients with stage III ovarian cancer who underwent cytoreductive surgery at Hebei University Affiliated Hospital between 2020 and 2023. Patients were randomly assigned to three groups: a 3D visualization group, a 3D visualization plus 3D printing group, and a traditional 2D CT imaging evaluation group. High-precision medical imaging techniques (e.g., CT, MRI) were employed to create digital 3D models, which were then converted into physical entities using 3D printing for surgical planning and simulation. Results: Both the 3D visualization group and the 3D visualization plus 3D printing group demonstrated superior outcomes in terms of surgery duration and blood loss compared to the traditional 2D CT group, indicating the efficacy of 3D reconstruction and 3D printing in preoperative planning. Postoperative recovery indicators, such as hospital stay and time to first flatus, were also more favorable in the groups utilizing 3D technology. Although there were no significant differences in postoperative complications and recurrence rates among the three groups, the groups using 3D technology showed advantages in reducing certain complications. Conclusions: The results indicate that medical 3D technology has significant value in the surgical planning of advanced ovarian cancer, enhancing surgical precision and reducing intraoperative risks, which may aid in improving postoperative recovery.
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OBJECTIVE: 5-aminolevulinic acid (5-ALA) is a precursor of the photosensitizer and photodynamic therapy (PDT) has been used in clinical practice. However, tumor cellular hypoxia severely affects the efficiency of photodynamic therapy. In this study, photodynamic therapy was combined with tirapazamine to investigate the effects of the combined intervention and the related mechanisms it may involve. METHODS: Colony formation assays were used to demonstrate cell proliferation. Transwell assays were performed to observe the effect on cell invasion and metastasis after the corresponding intervention. DCFH-DA probe was used to detect the reactive oxygen species content. Flow cytometry was used to detect the effects of the interventions on apoptosis and cell cycle. The relevant pathways that may be involved are explored by examining the expression levels of the relevant proteins and genes. RESULTS: Colony formation assays indicated that the combined intervention inhibited cell proliferation. Transwell assays demonstrated that PDT combined with TPZ effectively inhibited tumor cell invasion and metastasis. In addition, fluorescence intensity generated by DCFH-DA oxidation was detected indicating that the combined intervention increased the formation of reactive oxygen species. Flow cytometry clearly showed that the combination of PDT and TPZ further increased apoptosis and cell cycle arrest. The results of western blotting and qRT-PCR experiments confirmed that the combination therapy inhibited HIF-1α/VEGF axis and the PI3K/Akt/mTOR pathway activation. CONCLUSION: 5-ALA-PDT combined with TPZ can inhibit cell proliferation, increase apoptosis, and inhibit the PI3K/Akt/mTOR pathway, thus inhibiting tumor growth and metastasis and improving anti-cancer effects.
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OBJECTIVES: This study aimed to investigate the involvement of the cell cycle-related protein centromere protein F (CENPF) in the development of ovarian cancer (OC) and explored its relationship with ferroptosis. DESIGN: The databases were analysed to identify differential expression of cell cycle-related proteins between individuals with OC and normal individuals. Immunohistochemistry and statistical analysis were conducted on ovarian tissues obtained from 40 patients with epithelial OC and 20 normal individuals. In vitro experiments were performed using SKOV3 and HEY epithelial OC cell lines. PARTICIPANTS/MATERIALS, SETTING, METHODS: The mRNA microarray dataset, consisting of GSE14001, GSE54388, GSE40595, and GSE14407, was downloaded from the Gene Expression Omnibus (GEO) database to investigate the genes associated with cell cycle regulation in OC cells. CENPF was selected as the subject of study through differential analysis.Assessed the expression of CENPF in both OC patients and normal ovarian tissues using immunohistochemistry. Lentivirus infection was employed to downregulate CENPF expression, and subsequent experiments including Cell Counting Kit-8 assay, cell cycle analysis, transwell assay, and wound-healing assay were conducted to investigate the effects of CENPF on proliferation, invasion, migration, and cell cycle regulation in OC cells. The reactive oxygen species (ROS) and the malondialdehyde (MDA) assays were performed to assess the involvement of CENPF in cellular redox reactions. Western blot analysis was conducted to examine the expression levels of ferroptosis-related proteins (GPX4, SLC7A11, DMT1, and protein 53 [p53]). RESULTS: By querying and integrating cell cycle-related genes from the GEO database, in silico analyses using The Cancer Genome Atlas database combined with immunohistochemical studies, we discovered that CENPF is upregulated in OC tissues and is related to survival. Downregulation of CENPF inhibited biological function of OC cells, increased intracellular ROS and MDA levels, and downregulated the GPX4 protein and the SLC7A11/xCT protein, but upregulated the DMT1 protein and the tumour p53 expression to induce ferroptosis. LIMITATIONS: This study did not investigate ferroptosis-related studies following CENPF overexpression, and the findings have not been validated in animal studies. CONCLUSIONS: Our findings demonstrated that the deficiency of CENPF played a crucial anti-oncogenic role in the progression of OC through the mechanism of ferroptosis.
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Background: Ginsenoside 20(S)-Rg3 shows promising tumor-suppressive effects in ovarian cancer via inhibiting NF-κB signaling. This study aimed to explore the downstream tumor suppressive mechanisms of ginsenoside Rg3 via this signaling pathway. Materials and methods: A systematical screening was applied to examine the expression profile of 41 kinesin family member genes in ovarian cancer. The regulatory effect of ginsenoside Rg3 on KIF20A expression was studied. In addition, we explored interacting proteins of KIF20A and their molecular regulations in ovarian cancer. RNA-seq data from The Cancer Genome Atlas (TCGA) was used for bioinformatic analysis. Epithelial ovarian cancer cell lines SKOV3 and A2780 were used as in vitro and in vivo cell models. Commercial human ovarian cancer tissue arrays were used for immunohistochemistry staining. Results: KIF20A is a biomarker of poor prognosis among the kinesin genes. It promotes ovarian cancer cell growth in vitro and in vivo. Ginsenoside Rg3 can suppress the transcription of KIF20A. GST pull-down and co-immunoprecipitation (IP) assays confirmed that KIF20A physically interacts with BTRC (ß-TrCP1), a substrate recognition subunit for SCFß-TrCP E3 ubiquitin ligase. In vitro ubiquitination and cycloheximide (CHX) chase assays showed that via interacting with BTRC, KIF20A reduces BTRC-mediated CDC25A poly-ubiquitination and enhances its stability. Ginsenoside Rg3 treatment partly abrogates KIF20A overexpression-induced CDC25A upregulation. Conclusion: This study revealed a novel anti-tumor mechanism of ginsenoside Rg3. It can inhibit KIF20A transcription and promote CDC25A proteasomal degradation in epithelial ovarian cancer.
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A growing amount of experimental evidence has proven that the application of gold nanorods (AuNRs) in photodynamic therapy (PDT) can significantly enhance its therapeutic efficacy. The aim of this study was to establish a protocol for investigating the effect of gold nanorods loaded with the photosensitizer chlorin e6 (Ce6) on photodynamic therapy in the OVCAR3 human ovarian cancer cell line in vitro and to determine whether the PDT effect was different from that of Ce6 alone. OVCAR3 cells were randomly divided into three groups: the control group, Ce6-PDT group, and AuNRs@SiO2@Ce6-PDT group. Cell viability was measured by MTT assay. The generation of reactive oxygen species (ROS) was measured by a fluorescence microplate reader. Cell apoptosis was detected by flow cytometry. The expression of apoptotic proteins was detected by immunofluorescence and western blotting. The results showed that compared with that of the Ce6-PDT group, the cell viability of the AuNRs@SiO2@Ce6-PDT group was significantly decreased (P < 0.05) in a dose-dependent manner, and ROS production increased significantly (P < 0.05). The flow cytometry results showed that the proportion of apoptotic cells in the AuNRs@SiO2@Ce6-PDT group was significantly higher than that in the Ce6-PDT group (P < 0.05). Immunofluorescence and western blot results showed that the protein expression levels of cleaved caspase-9, cleaved caspase-3, cleaved PARP, and Bax in the AuNRs@SiO2@Ce6-PDT-treated-OVCAR3 cells were higher than those in the Ce6-PDT-treated cells (P < 0.05), and the protein expression levels of caspase-3, caspase-9, PARP, and Bcl-2 were slightly lower than those in the Ce6-PDT group (P < 0.05). In summary, our results show that AuNRs@SiO2@Ce6-PDT has a significantly stronger effect on OVCAR3 cells than the effect of Ce6-PDT alone. The mechanism may be related to the expression of Bcl-2 family and caspase family in the mitochondrial pathway.
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Clorofilidas , Nanotubos , Neoplasias Ováricas , Fotoquimioterapia , Porfirinas , Humanos , Femenino , Fotoquimioterapia/métodos , Caspasa 3/metabolismo , Dióxido de Silicio , Caspasa 9/metabolismo , Apoptosis , Especies Reactivas de Oxígeno/metabolismo , Línea Celular Tumoral , Oro/farmacología , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacología , Neoplasias Ováricas/tratamiento farmacológico , Fármacos Fotosensibilizantes/farmacología , Porfirinas/farmacología , Clorofilidas/farmacologíaRESUMEN
PURPOSE: This article explores the effect of 5-aminolevulinic acid (5-ALA)-mediated photodynamic therapy (PDT) combined with cisplatin (CDDP) on the apoptosis of human ovarian cancer cells and the mechanism of action of the combination therapy. MATERIALS AND METHODS: Human ovarian cancer OVCAR-3 âcells were cultured in vitro and divided into 5-ALA/PDT group, CDDP group and combined treatment group (5-ALA/PDT combined with different concentrations of CDDP). After administration of the corresponding drugs, a CCK-8 assay was used to detect the inhibition rate of cell proliferation. After Rhodamine 123 staining, mitochondrial membrane potential changes were observed under fluorescence microscopy. The apoptosis rate and reactive oxygen species (ROS) content were detected by flow cytometry. Western blotting was used to detect protein expression. RESULTS: The CCK-8 assay showed that CDDP in combination with 5-ALA/PDT significantly enhanced cytotoxicity compared to treatment with CDDP alone and that low doses of CDDP were sufficient to induce these combination effects. The mitochondrial membrane potential in each combination treatment group gradually decreased with increasing CDDP concentration, while the apoptosis rate and reactive oxygen species (ROS) content detected by flow cytometry gradually increased. Western blotting assay showed that the expression of bax, cleaved caspase-9, cleaved caspase-3, and cleaved PARP was increased, while the expression of bcl-2, caspase-9, caspase-3, and PARP was decreased, and the differences were statistically significant (P â< â0.05). CONCLUSIONS: In summary, 5-ALA/PDT combined with CDDP can effectively inhibit cell proliferation and promote apoptosis, and this combination may induce apoptosis by activating the mitochondrial pathway.
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Neoplasias Ováricas , Fotoquimioterapia , Humanos , Femenino , Ácido Aminolevulínico/farmacología , Ácido Aminolevulínico/uso terapéutico , Cisplatino/farmacología , Cisplatino/uso terapéutico , Cisplatino/metabolismo , Fármacos Fotosensibilizantes/farmacología , Especies Reactivas de Oxígeno/metabolismo , Caspasa 3/metabolismo , Caspasa 9/metabolismo , Caspasa 9/farmacología , Apoptosis , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacología , Neoplasias Ováricas/tratamiento farmacológico , Línea Celular TumoralRESUMEN
A single-longitudinal-mode (SLM), narrow linewidth thulium-doped fiber laser with a sampled fiber Bragg grating (SFBG), switchable among three wavelengths, with a cascade dual-coupler-ring-based compound cavity (DCR-CC) filter, is proposed and demonstrated. The coupling design, simulation analysis, and characterization of the DCR-CC filter provide the foundation for the experiment. A nonlinear polarization rotation system was injected into the cavity to suppress gain competition and achieve a laser switchable among three wavelengths. The fluctuations of the wavelength and power of the output laser are less than 0.60 nm and 0.91 dBm, respectively. For demonstration, the laser maintained in SLM operation measured by the delayed self-heterodyne method has a linewidth of <3.7k H z and relative intensity noise of <-114d B/H z.
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We propose and demonstrate a high-performance wavelength-switchable erbium-doped fiber laser (EDFL), enabled by a figure-8 compound-ring-cavity (F8-CRC) filter for single-longitudinal-mode (SLM) selection and a polarization-managed four-channel filter (PM-FCF) for defining four lasing wavelengths. We introduce a novel methodology utilizing signal-flow graph combined with Mason's rule to analyze a CRC filter in general and apply it to obtain the important design parameters for the F8-CRC used in this paper. By combining the functions of the F8-CRC filter and the PM-FCF assisted by the enhanced polarization hole-burning and polarization dependent loss, we achieve the EDFL with fifteen lasing states, including four single-, six dual-, four tri- and one quad-wavelength lasing operations. In particular, all the four single-wavelength operations are in stable SLM oscillation, typically with a linewidth of <600 Hz, a RIN of ≤-154.58 dB/Hz@≥3 MHz and an output power fluctuation of ≤±3.45%. In addition, all the six dual-wavelength operations have very similar performances, with the performance parameters close to those of the four single-wavelength operations, superior to our previous work and others' similar work significantly. Finally, we achieve the wavelength-spacing tuning of dual-wavelength operations for photonic generation of tunable microwave signals, and successfully obtain a signal at 23.10 GHz as a demonstration.
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This research experimentally demonstrates a switchable, single-wavelength, thulium-doped fiber laser based on the cascading of a multimode-single-mode-multimode (MSM) fiber filter and a two-mode fiber (TMF) filter. When the MSM fiber filter suffers from bending, the blue-shift of the output spectrum can be obtained. A switchable lasing wavelength output is realized by bending the MSM fiber filter to cover different channels of the TMF filter. The output wavelength can be switched from 1982.54 to 1938.81 nm with an optical signal-to-noise ratio of higher than 40 dB. The wavelength interval of the switchable output is an integral multiple of the wavelength interval of the TMF filter. The stability of the output wavelength was tested within 60 min, and the wavelength shift and output power fluctuation were found to be less than 0.01 nm and 0.31 dB, respectively, which demonstrates a stable output performance.
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We aimed to investigate the mechanism and effect of photodynamic treatment mediated by 5-aminoketovalerate (5-ALA-PDT) on human ovarian cancer cells (OVCAR3 cells) and to provide a theoretical basis for the subsequent experimental step in vivo. Human ovarian cancer OVCAR3 cells were randomly divided into four groups: control group, laser irradiation alone group, photosensitizer alone group, and photodynamic treatment group. Alterations in cell morphology were observed with an inverted light microscope; cell viability was examined by CCK-8 assays. The ROS content and apoptosis rate were examined by flow cytometry analysis. Western blot was used to detect the expression of apoptosis-related proteins, such as caspase-3, Bax, and Bcl-2, and the expression of cleaved caspase-3 in live cells was detected by a cleaved caspase-3 assay kit. Inverted light microscopy showed alterations in cell morphology in different stages. Comparison with the three other groups indicated that tumor cell proliferation was significantly decreased in the photodynamic treatment group (P < 0.05). Flow cytometry analysis revealed that the content of ROS was higher in the photodynamic group than in the other three groups, and the apoptosis rate was higher in the photodynamic treatment group. The difference compared with the other three groups was statistically significant (P < 0.001). The western blot results indicated that the protein expression of Bcl-2 and caspase-3 was decreased in the photodynamic treatment group, and the protein expression level of Bax was increased (P < 0.05). The expression of cleaved caspase-3 was increased in the photodynamic treatment group compared with the other groups according to the data obtained with a microplate reader. Thus, our results demonstrated that the apoptosis and viability of OVCAR3 cells are altered in response to 5-ALA-PDT; however, no remarkable effects were observed in ovarian cancer cells treated with laser irradiation or photosensitizer alone. 5-ALA-PDT can significantly inhibit the growth of human ovarian cancer cells, and the mechanism of this effect is related to the tumor cell apoptosis mediated by the downregulation of Bcl-2 and caspase-3 and upregulation of Bax protein expression.
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Neoplasias Ováricas , Fotoquimioterapia , Apoptosis , Línea Celular Tumoral , Femenino , Humanos , Neoplasias Ováricas/tratamiento farmacológico , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéuticoRESUMEN
BACKGROUND: Ovarian cancer, the malignant tumor with the highest mortality rate in gynecological tumors, leads to a poor prognosis due to tumor metastasis. At present, the main treatment for ovarian cancer is the combination of cytoreduction surgery and chemotherapy. But the surgery is insufficient to solve the extensive transfer of tumor in the abdominal cavity and a large proportion of ovarian cancer cases have shown resistance to chemotherapy. Photodynamic therapy (PDT) is a viable treatment option for a wide range of applications, especially in malignant tumors. Porphyrin sensitizers, as the most widely used photosensitive agents, have the following advantages: short photosensitive period and high singlet oxygen production. However, most studies have found that it is difficult to achieve high loading rates of photosensitive agents, thus effective concentration in target tissue is suboptimal and the lethal ability is greatly reduced. In this article, we review several studies that nanoparticles loading porphyrin sensitizers for photodynamic therapy of ovarian cancer. METHODS: We collected relevant literature from PUBMED and reviewed their research content. RESULTS: The application of nanotechnology to PDT in ovarian cancer can reduce the non-specific toxicity of photosensitive agents and increase stability and delivery efficiency. CONCLUSIONS: The combination with nanotechnology can cover the shortcomings of photodynamic therapy, but the specific efficacy still needs a large number of experiments to prove.
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Nanopartículas , Neoplasias Ováricas , Fotoquimioterapia , Porfirinas , Femenino , Humanos , Neoplasias Ováricas/tratamiento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/uso terapéuticoRESUMEN
Ensconsin is encoded by the MAP7 gene and belongs to the microtubule-associated proteins. This study aimed to explore its functional roles and partners in cell-cycle progression in cervical cancer. Data from the Cancer Genome Atlas-Cervical & Endocervical Cancer (TCGA-CESC) and the Genotype-Tissue Expression project were used for bioinformatic analysis. SiHa cells were used for in-vitro and in-vivo analysis. Co-immunoprecipitation (Co-IP) assay was conducted to explore the proteins interacted with MAP7. Results showed that MAP7 mRNA expression might serve as an independent biomarker of shorter survival. MAP7 overexpression elevated cyclin D1/cyclin B1 expression, facilitated cell-cycle progression and promoted SiHa cell growth in a xenograft tumor model. Co-IP experiments confirmed a novel interaction between MAP7 and RC3H1. Knockdown of either RC3H1 or MAP7 significantly attenuated cyclin D1/cyclin B1 upregulation, and cell-cycle progression induced by the other partner. MAP7 overexpression led to increased expression of P-IKK (Ser176/177) and P-p65 (Ser536). RC3H1 inhibition abrogated MAP7 induced upregulation of P-IKK and P-p65. Data in TCGA-CESC showed that MAP7 expression was positively correlated with its copy number segments, but was negatively correlated with the methylation level of three CpG sites within the gene locus. Demethylation treatment by 5-Aza-dC elevated both MAP7 mRNA and protein expression in a dose-dependent manner. In conclusion, this study revealed a novel interaction between MAP7 and RC3H1 in cervical cancer cells, which cooperatively enhanced cyclin D1/cyclin B1 expression and facilitated cell-cycle progression. These effects were at least partly mediated by activated canonical IKK/NF-kB signaling.
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Proteínas Asociadas a Microtúbulos , FN-kappa B , Mapas de Interacción de Proteínas , Proteínas de Unión al ARN , Ubiquitina-Proteína Ligasas , Neoplasias del Cuello Uterino , Femenino , Humanos , Ciclo Celular , Línea Celular Tumoral , Proteínas Asociadas a Microtúbulos/metabolismo , FN-kappa B/metabolismo , Proteínas de Unión al ARN/metabolismo , Transducción de Señal , Ubiquitina-Proteína Ligasas/metabolismo , Neoplasias del Cuello Uterino/metabolismo , Neoplasias del Cuello Uterino/patologíaRESUMEN
Salusin-ß, a multifunctional bioactive peptide, is considered as a promising candidate biomarker for predicting cardiovascular diseases. This study was designed to determine whether inhibition of salusin-ß in the hypothalamic paraventricular nucleus (PVN) delays the progression of hypertension and attenuates cardiac hypertrophy by restoring neurotransmitters and cytokines. Male Sprague Dawley rats were fed with a normal salt diet (NS, 0.3%) or a high salt diet (HS, 8%) for 8 weeks to induce hypertension. Then, these rats received bilateral PVN infusion of a specific salusin-ß blocker, antisalusin-ß IgG (SIgG), or control IgG (CIgG) for 2 weeks. HS rats exhibited higher mean arterial pressure and cardiac hypertrophy as indicated by increased whole heart weight/bodyweight ratio, whole heart weight/tibia length ratio, left ventricular weight/tibia length ratio, and messenger RNA levels of cardiac atrial natriuretic peptide (ANP), and ß-myosin heavy chain. Compared with NS rats, HS rats had higher levels of glutamate, norepinephrine, tyrosine hydroxylase, proinflammatory cytokines, and lower levels of gamma-aminobutyric acid, interleukin 10, and the 67-kDa isoform of glutamate decarboxylase (GAD67) in the PVN, and higher plasma levels of proinflammatory cytokines. Chronic PVN infusion of SIgG attenuated all these changes in HS rats. Our findings suggest that HS rats have an imbalance between excitatory and inhibitory neurotransmitters, as well as an imbalance between proinflammatory and anti-inflammatory cytokines in the PVN; and chronic inhibition of salusin-ß in the PVN restores neurotransmitters and cytokines in the PVN, thereby attenuating hypertensive responses and cardiac hypertrophy.
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Anticuerpos Monoclonales/uso terapéutico , Cardiomegalia/prevención & control , Hipertensión/tratamiento farmacológico , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Núcleo Hipotalámico Paraventricular/efectos de los fármacos , Cloruro de Sodio Dietético/efectos adversos , Animales , Anticuerpos Monoclonales/administración & dosificación , Presión Sanguínea/efectos de los fármacos , Cardiomegalia/etiología , Cardiomegalia/inmunología , Cardiomegalia/metabolismo , Citocinas/inmunología , Modelos Animales de Enfermedad , Expresión Génica/efectos de los fármacos , Hipertensión/etiología , Hipertensión/inmunología , Hipertensión/metabolismo , Péptidos y Proteínas de Señalización Intercelular/genética , Péptidos y Proteínas de Señalización Intercelular/inmunología , Masculino , Neurotransmisores/metabolismo , Núcleo Hipotalámico Paraventricular/metabolismo , Ratas Sprague-DawleyRESUMEN
Reactive oxygen species (ROS) in the brain plays an important role in the progression of hypertension and hydrogen peroxide (H2O2) is a major component of ROS. The aim of this study is to explore whether endogenous H2O2 changed by polyethylene glycol-catalase (PEG-CAT) and aminotriazole (ATZ) in the hypothalamic paraventricular nucleus (PVN) regulates neurotransmitters, renin-angiotensin system (RAS), and cytokines, and whether subsequently affects the renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) in high salt-induced hypertension. Male Sprague-Dawley rats received a high-salt diet (HS, 8% NaCl) or a normal-salt diet (NS, 0.3% NaCl) for 10 weeks. Then rats were treated with bilateral PVN microinjection of PEG-CAT (0.2 i.u./50nl), an analog of endogenous catalase, the catalase inhibitor ATZ (10nmol/50nl) or vehicle. High salt-fed rats had significantly increased MAP, RSNA, plasma norepinephrine (NE) and pro-inflammatory cytokines (PICs). In addition, rats with high-salt diet had higher levels of NOX-2, NOX-4 (subunits of NAD(P)H oxidase), angiotensin-converting enzyme (ACE), interleukin-1beta (IL-1ß), glutamate and NE, and lower levels of gamma-aminobutyric acid (GABA) and interleukin-10 (IL-10) in the PVN than normal diet rats. Bilateral PVN microinjection of PEG-CAT attenuated the levels of RAS and restored the balance of neurotransmitters and cytokines, while microinjection of ATZ into the PVN augmented those changes occurring in hypertensive rats. Our findings demonstrate that ROS component H2O2 in the PVN regulating MAP and RSNA are partly due to modulate neurotransmitters, renin-angiotensin system, and cytokines within the PVN in salt-induced hypertension.
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Amitrol (Herbicida)/farmacología , Catalasa/farmacología , Peróxido de Hidrógeno/metabolismo , Hipertensión/inducido químicamente , Núcleo Hipotalámico Paraventricular/metabolismo , Polietilenglicoles/farmacología , Cloruro de Sodio Dietético/toxicidad , Animales , Presión Sanguínea/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Masculino , Neurotransmisores/sangre , Neurotransmisores/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
OBJECTIVE: To evaluate the efficacy and safety of Jinying Capsule (JC) in treating pelvic inflammatory disease patients with accumulated damp-heat syndrome (ADHS). METHODS: Totally 328 patients were recruited in a prospective, positive drug parallel controlled, and multi-center clinical trial. Of them 213 patients in the treatment group took JC (0.5 g per capsule), 4 capsules each time, 3 times per day, while 115 patients in the control group took Kangfuyan Capsule (KC, 0.4 g per capsule), 3 capsules each time, twice per day. The course of treatment was 4 weeks for all. Scores of Chinese medical syndromes, visual analogue scale (VAS) of the lower abdominal pain, and European quality of life-five dimension scale (EQ-5D) were observed before treatment and after 4 weeks of treatment. RESULTS: There were 204 patients in the treatment group and 109 in the control group who completed this trial. The total effective rate of Chinese medical syndrome was 89.71% (183/204 cases) in the treatment group and 76.15% (83/109 cases) in the control group (P < 0.01). Compared with before treatment in the same group, EQ-5D scores increased, and VAS scores of the lower abdominal pain decreased in the two groups after treatment. EQ-5D scores was 0.857 ± 0.157 in the treatment group, obviously higher than that in the control group (0.753 ± 0.126, P < 0.05). VAS scores of the lower abdominal pain was 2.14 ± 1.23 in the treatment group, lower than that in the control group (2.33 ± 1.24), but with no statistical difference between the two groups (P > 0.05). No adverse reaction occurred in the two groups. CONCLUSION: JC was superior to KC in improving Chinese medical syndrome and quality of life of pelvic inflammatory disease patients with accumulated damp-heat syndrome.
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Medicamentos Herbarios Chinos/uso terapéutico , Medicina Tradicional China , Enfermedad Inflamatoria Pélvica/tratamiento farmacológico , Cápsulas , Femenino , Calor , Humanos , Fitoterapia , Estudios Prospectivos , Calidad de Vida , Seguridad , SíndromeRESUMEN
AIMS: Regular exercise as an effective non-pharmacological antihypertensive therapy is beneficial for prevention and control of hypertension, but the central mechanisms are unclear. In this study, we hypothesized that chronic exercise training (ExT) delays the progression of hypertension and attenuates cardiac hypertrophy by up-regulating anti-inflammatory cytokines, reducing pro-inflammatory cytokines (PICs) and restoring the neurotransmitters balance in the hypothalamic paraventricular nucleus (PVN) in young spontaneously hypertensive rats (SHR). In addition, we also investigated the involvement of nuclear factor-κB (NF-κB) p65 and NAD(P)H oxidase in exercise-induced effects. METHODS AND RESULTS: Moderate-intensity ExT was administrated to young normotensive Wistar-Kyoto (WKY) and SHR rats for 16 weeks. SHR rats had a significant increase in mean arterial pressure and cardiac hypertrophy. SHR rats also had higher levels of glutamate, norepinephrine (NE), phosphorylated IKKß, NF-κB p65 activity, NAD(P)H oxidase subunit gp91(phox), PICs and the monocyte chemokine protein-1 (MCP-1), and lower levels of gamma-aminobutyric acid (GABA) and interleukin-10 (IL-10) in the PVN. These SHR rats also exhibited higher renal sympathetic nerve activity (RSNA), and higher plasma levels of PICs, and lower plasma IL-10. However, ExT ameliorates all these changes in SHR rats. CONCLUSION: These findings suggest that there are the imbalances between excitatory and inhibitory neurotransmitters and between pro- and anti-inflammatory cytokines in the PVN of SHR rats, which at least partly contributing to sympathoexcitation, hypertension and cardiac hypertrophy; chronic exercise training attenuates hypertension and cardiac hypertrophy by restoring the balances between excitatory and inhibitory neurotransmitters and between pro- and anti-inflammatory cytokines in the PVN; NF-κB and oxidative stress in the PVN may be involved in these exercise-induced effects.
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Presión Arterial/fisiología , Cardiomegalia/terapia , Citocinas/metabolismo , Hipertensión/terapia , Núcleo Hipotalámico Paraventricular/metabolismo , Condicionamiento Físico Animal/fisiología , Animales , Cardiomegalia/metabolismo , Cardiomegalia/fisiopatología , Ácido Glutámico/metabolismo , Hipertensión/metabolismo , Hipertensión/fisiopatología , Masculino , NADPH Oxidasas/metabolismo , FN-kappa B/metabolismo , Norepinefrina/metabolismo , Estrés Oxidativo/fisiología , Ratas , Ratas Endogámicas SHR , Ratas Endogámicas WKY , Sistema Nervioso Simpático/metabolismo , Sistema Nervioso Simpático/fisiopatología , Ácido gamma-Aminobutírico/metabolismoRESUMEN
The renin-angiotensin system (RAS) in the brain is involved in the pathogenesis of hypertension. We hypothesized that inhibition of angiotensin-converting enzyme (ACE) in the hypothalamic paraventricular nucleus (PVN) attenuates angiotensin II (ANG II)-induced hypertension via restoring neurotransmitters and cytokines. Rats underwent subcutaneous infusions of ANG II or saline and bilateral PVN infusions of ACE inhibitor enalaprilat (ENL, 2.5µg/h) or vehicle for 4weeks. ANG II infusion resulted in higher mean arterial pressure and cardiac hypertrophy as indicated by increased whole heart weight/body weight ratio, whole heart weight/tibia length ratio, left ventricular weight/tibia length ratio, and mRNA expressions of cardiac atrial natriuretic peptide and beta-myosin heavy chain. These ANG II-infused rats had higher PVN levels of glutamate, norepinephrine, tyrosine hydroxylase, pro-inflammatory cytokines (PICs) and the chemokine monocyte chemoattractant protein-1, and lower PVN levels of gamma-aminobutyric acid, interleukin (IL)-10 and the 67-kDa isoform of glutamate decarboxylase (GAD67), and higher plasma levels of PICs, norepinephrine and aldosterone, and lower plasma IL-10, and higher renal sympathetic nerve activity. However, PVN treatment with ENL attenuated these changes. PVN microinjection of ANG II induced increases in IL-1ß and IL-6, and a decrease in IL-10 in the PVN, and pretreatment with angiotensin II type 1 receptor (AT1-R) antagonist losartan attenuated these changes. These findings suggest that ANG II infusion induces an imbalance between excitatory and inhibitory neurotransmitters and an imbalance between pro- and anti-inflammatory cytokines in the PVN, and PVN inhibition of the RAS restores neurotransmitters and cytokines in the PVN, thereby attenuating ANG II-induced hypertension and cardiac hypertrophy.
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Cardiomegalia/tratamiento farmacológico , Enalaprilato/uso terapéutico , Hipertensión/tratamiento farmacológico , Angiotensina II/efectos adversos , Animales , Cardiomegalia/inducido químicamente , Quimiocina CCL2/metabolismo , Enalaprilato/administración & dosificación , Ácido Glutámico/sangre , Corazón/efectos de los fármacos , Hipertensión/inducido químicamente , Interleucina-10/sangre , Interleucina-1beta/sangre , Interleucina-6/sangre , Riñón/efectos de los fármacos , Riñón/metabolismo , Losartán/farmacología , Masculino , Neurotransmisores/metabolismo , Norepinefrina/sangre , Tamaño de los Órganos/efectos de los fármacos , Núcleo Hipotalámico Paraventricular/efectos de los fármacos , Núcleo Hipotalámico Paraventricular/metabolismo , Peptidil-Dipeptidasa A/metabolismo , Ratas , Ratas Sprague-Dawley , Receptor de Angiotensina Tipo 1/metabolismo , Sistema Renina-Angiotensina/efectos de los fármacos , Ácido gamma-Aminobutírico/sangreRESUMEN
Angiotensin II type 1 receptor (AT1-R) and nuclear factor-kappaB (NF-κB) in the paraventricular nucleus (PVN) play important roles in heart failure (HF); however, the central mechanisms by which AT1-R and NF-κB contribute to sympathoexcitation in HF are yet unclear. In this study, we determined whether interaction between AT1-R and NF-κB in the PVN modulates neurotransmitters and contributes to NAD(P)H oxidase-dependent oxidative stress and sympathoexcitation in HF. Rats were implanted with bilateral PVN cannulae and subjected to coronary artery ligation or sham surgery (SHAM). Subsequently, animals were treated for 4 weeks through bilateral PVN infusion with either vehicle or losartan (LOS, 10 µg/h), an AT1-R antagonist; or pyrrolidine dithiocarbamate (PDTC, 5 µg/h), a NF-κB inhibitor via osmotic minipump. Myocardial infarction (MI) rats had higher levels of glutamate (Glu), norepinephrine (NE) and NF-κB p65 activity, lower levels of gamma-aminobutyric acid (GABA), and more positive neurons for phosphorylated IKKß and gp91(phox) (a subunit of NAD(P)H oxidase) in the PVN when compared to SHAM rats. MI rats also had higher levels of renal sympathetic nerve activity (RSNA) and plasma proinflammatory cytokines (PICs), NE and epinephrine. PVN infusions of LOS or PDTC attenuated the decreases in GABA and the increases in gp91(phox), NF-κB activity, Glu and NE, in the PVN of HF rats. PVN infusions of LOS or PDTC also attenuated the increases in RSNA and plasma PICs, NE and epinephrine in MI rats. These findings suggest that interaction between AT1 receptor and NF-κB in the PVN contributes to oxidative stress and sympathoexcitation by modulating neurotransmitters in heart failure.
Asunto(s)
Insuficiencia Cardíaca/metabolismo , FN-kappa B/metabolismo , Estrés Oxidativo/fisiología , Núcleo Hipotalámico Paraventricular/metabolismo , Receptor de Angiotensina Tipo 1/metabolismo , Fibras Simpáticas Posganglionares/metabolismo , Animales , Losartán/farmacología , Masculino , FN-kappa B/antagonistas & inhibidores , Neurotransmisores/fisiología , Estrés Oxidativo/efectos de los fármacos , Núcleo Hipotalámico Paraventricular/efectos de los fármacos , Unión Proteica/fisiología , Pirrolidinas/farmacología , Ratas , Ratas Sprague-Dawley , Fibras Simpáticas Posganglionares/efectos de los fármacos , Tiocarbamatos/farmacologíaRESUMEN
Angiotensin II (ANG II)-induced inflammatory and oxidative stress responses contribute to the pathogenesis of hypertension. In this study, we determined whether renin-angiotensin system (RAS) activation in the hypothalamic paraventricular nucleus (PVN) contributes to the ANG II-induced hypertensive response via interaction with neurotransmitters in the PVN. Rats underwent subcutaneous infusion of ANG II or saline for 4 weeks. These rats were treated for 4 weeks through bilateral PVN infusion with either vehicle or losartan (LOS), an angiotensin II type 1 receptor (AT1-R) antagonist, via osmotic minipump. ANG II infusion resulted in higher levels of glutamate, norepinephrine (NE), AT1-R and pro-inflammatory cytokines (PIC), and lower level of gamma-aminobutyric acid (GABA) in the PVN. Rats receiving ANG II also had higher levels of mean arterial pressure, plasma PIC, NE and aldosterone than control animals. PVN treatment with LOS attenuated these ANG II-induced hypertensive responses. In conclusion, these findings suggest that the RAS activation in the PVN contributes to the ANG II-induced hypertensive response via interaction with PIC and neurotransmitters (glutamate, NE and GABA) in the PVN.