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We present an analytical treatment of ultra-short pulses propagating in an optical fiber in the strong nonlinearity regime, in which the interaction between self-phase modulation (SPM) and group-velocity dispersion (GVD) substantially broadens the input spectrum. Supported by excellent agreement with the simulation results, these analytical solutions provide a convenient and reasonable accurate estimation of the peak position of the outermost spectral lobes as well as the full width at half maximum of the broadened spectrum. We show that our unified solutions are valid for either Gaussian pulse or hyperbolic secant pulse propagating inside an optical fiber with positive or negative GVD. Our findings shed light on the optimization of SPM-enabled spectral broadening in various applications.
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The development and progression of the complications of chronic diabetes mellitus are attributed not only to increased blood glucose levels but also to glycemic variability. Therefore, a deeper understanding of the role of glycemic variability in the development of diabetic complications may provide more insight into targeted clinical treatment strategies in the future. Previously, the mechanisms implicated in glycemic variability-induced diabetic complications have been comprehensively discussed. However, endothelial dysfunction and platelet hyperactivation, which are two newly recognized critical pathogenic factors, have not been fully elucidated yet. In this review, we first evaluate the assessment of glycemic variability and then summarise the roles of endothelial dysfunction and platelet hyperactivation in glycemic variability-induced complications of diabetes, highlighting the molecular mechanisms involved and their interconnections.
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Complicações do Diabetes , Diabetes Mellitus Tipo 2 , Doenças Vasculares , Glicemia , Complicações do Diabetes/etiologia , Hemoglobinas Glicadas/análise , HumanosRESUMO
The prethrombotic state (PTS) is a possible cause of recurrent spontaneous abortion (RSA). The aim of this study was to identify serum biomarkers for the detection of RSA with PTS (PSRSA). A Quantibody array 440 was used to screen novel serum-based biomarkers for PSRSA/NRSA (RSA without PTS). Proteins differentially expressed in PSRSA were analysed using bioinformatics methods and subjected to a customized array and enzyme-linked immunosorbent assay (ELISA) validation. We used receiver operating characteristic to calculate diagnostic accuracy, and machine learning methods to establish a biomarker model for evaluation of the identified targets. 20 targets were selected for validation using a customized array, and seven targets via ELISA. The decision tree model showed that IL-24 was the first node and eotaxin-3 was the second node distinguishing the PSRSA and NRSA groups (an accuracy rate of 100% and an AUC of 1). Epidermal growth factor (EGF) as the node distinguished the PSRSA and NC groups (an accuracy rate of 100% and an AUC of 1). EGF as the node distinguished the NRSA and NC groups (an accuracy rate of 96.5% and an AUC of 0.998). Serum DNAM-1, BAFF, CNTF, LAG-3, IL-24, Eotaxin-3 and EGF represent a panel of promising diagnostic biomarkers to detect the PSRSA.
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Aborto Habitual/sangue , Biomarcadores/sangue , Fator de Crescimento Epidérmico/sangue , Interleucinas/sangue , Aborto Habitual/patologia , Adulto , Antígenos de Diferenciação de Linfócitos T/sangue , Fator Ativador de Células B/sangue , Quimiocina CCL26/sangue , Fator Neurotrófico Ciliar/sangue , Biologia Computacional , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Gravidez , Curva ROC , Adulto JovemRESUMO
We demonstrate, to the best of our knowledge, the first double-pass pre-chirp managed fiber amplifier. The double-pass fiber amplifier exhibits high gain allowing us to amplify chirped picosecond pulses from 20 mW to 113 W in a rod-type Yb-fiber corresponding to 38 dB gain. We study the dependence of static mode degradation (SMD) on the nonlinear phase shift (NPS) accumulated by the amplified pulse. Our results indicate that a larger nonlinear phase shift results in stronger nonlinear polarization evolution of the fundamental mode and leads to a lower threshold for SMD. After optimization, our pre-chirp managed amplifier seeded by 80 mW pulses delivers 102 W amplified power from the main output. The amplified pulses are compressed to 37 (55) fs with 90 (100) W average power by a grating pair (chirped mirrors). The double-pass configuration significantly simplifies the implementation of pre-chirp managed fiber amplifiers leading to an extremely compact system.
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To examine the therapeutic effect of Bushen Huoxue recipe (BHR) on women with thin endometrial ovulation disorder and on a rat model of kidney deficiency-related blood stasis. A total of 60 women with thin endometrial ovulation disorder was enrolled. The primary outcome of the study was the pregnancy rate three menstrual cycles after treatment. The study also examined the changes in the type and thickness of uterine artery, uterine artery pulsatility index (PI) and endometrial resistance index (RI). To establish kidney deficiency-related blood stasis in Sprague Dawley (SD) rats, an intragastric administration of hydroxyurea and a tail vein injection of Dextran were given, following with a flashing of the uterine cavity with 95% anhydrous ethanol. A combined regimen of BHR and estradiol valerate significantly increased the rate of pregnancy in women with thin endometrial ovulation disorder. The treatment was accompanied by a significant increase in endometrial thickness and decreases in uterine artery PI and endometrial RI. In rats, kidney deficiency-related blood stasis caused severe loss in endometrial architecture, thickness, and numbers of gland and blood vessel compared to the healthy SD rats. Treatment with BHR could ameliorate the endometrial damages associated with kidney deficiency-related blood stasis.
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Medicamentos de Ervas Chinesas/uso terapêutico , Endométrio/efeitos dos fármacos , Artéria Uterina/efeitos dos fármacos , Doenças Uterinas/tratamento farmacológico , Adulto , Animais , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Medicamentos de Ervas Chinesas/farmacologia , Feminino , Humanos , Nefropatias/complicações , Ovulação , Projetos Piloto , Gravidez , Taxa de Gravidez , Ratos Sprague-Dawley , Doenças Uterinas/etiologiaRESUMO
Several studies have focused on chemical agents, tailored from natural edible products, used to prevent and treat various diseases. ß-elemene is a well-known compound derived from Curcuma wenyujin that possesses a wide spectrum of anticancer properties under preclinical and clinical conditions. Several studies have demonstrated its inhibitory effect both in humans and animals with cancers. Numerous in vivo and in vitro experimental models have revealed that ß-elemene can modulate multiple molecular pathways involved in carcinogenesis. In general, (1) ß-elemene itself can inhibit and kill tumor cells through a variety of mechanisms, and (2) can synergistically enhance the effect of radiotherapy and/or chemotherapy, (3) also can regulate autoimmune in the treatment of tumors. In this article, we critically focused on the available scientific evidence discussing the use of ß-elemene in cancer prevention, and its molecular targets and mechanisms of action in different types of cancer. In addition, we have discussed its sources, chemistry, bioavailability, and future research directions.
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Antineoplásicos/farmacologia , Quimiorradioterapia , Neoplasias/tratamento farmacológico , Sesquiterpenos/farmacologia , Animais , Humanos , Tolerância a Radiação , Sesquiterpenos/química , Sesquiterpenos/farmacocinética , Sesquiterpenos/uso terapêuticoRESUMO
CONTEXT: Zuogui Wan is a classic traditional Chinese prescription. Preliminary studies have confirmed that it could improve sperm quality significantly. OBJECTIVE: To investigate the effect of Zuogui Wan on testis structure and c-kitproto-oncogeneprotein (c-Kit) and octamer-binding transcription factor-4 (Oct4) expression in a rat model of impaired spermatogenesis. MATERIAL AND METHODS: Thirty-six Sprague-Dawley (SD) rats were divided into Blank control, Tripterygium glycosides (GTW) and Zuogui Wan groups (n = 12). GTW was used to generate models of impaired spermatogenesis. Then Zuogui Wan group was administered 6 g/kg/d of Zuogui Wan granules for 4 weeks. Changes in the pathological structure and ultrastructure were observed with optical microscope and transmission electron microscope. Expression of c-Kit and Oct4 were quantified by RT qPCR and Western blots. RESULTS: Both the pathological damage and the damages in the ultrastructure of spermatogenic epithelium had improved in Zuogui Wan group. Compared with the GTW model group (0.47 ± 0.19; 0.38 ± 0.14), c-Kit and Oct4 protein expression increased in the Zuogui Wan group (0.75 ± 0.27; 0.65 ± 0.23). C-Kit and Oct4 mRNA expression increased in Zuogui Wan group (1.06 ± 0.16; 1.85 ± 1.04) compared to the GTW model group (0.66 ± 0.23; 0.46 ± 0.29). CONCLUSIONS: Zuogui Wan is capable of restoring the damage to the testis structure and ultrastructure and regulates the expression of c-Kit and Oct4 at protein and mRNA levels, inhibiting apoptosis and promoting proliferation of spermatogenic cells.
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Medicamentos de Ervas Chinesas/farmacologia , Fator 3 de Transcrição de Octâmero/metabolismo , Proteínas Proto-Oncogênicas c-kit/metabolismo , Testículo/efeitos dos fármacos , Testículo/metabolismo , Animais , Infertilidade Masculina , Masculino , Ratos , Ratos Sprague-Dawley , Espermatogênese/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Fator de Células-Tronco , Testículo/patologia , Testículo/ultraestruturaRESUMO
Acephalic spermatozoa syndrome (ASS) is characterized by a predominance of headless spermatozoa with abnormal head-tail junction in the ejaculate, which causes severe male infertility. The pathogenic mechanism of ASS remained unclarified for a long time until recent identification of the four ASS-associated genes SUN5, PMFBP1, TSGA10, and BRDT and their mutations due to the development of high-throughput sequencing technology. This review summarizes the advances in the genetic studies of ASS, focusing on its pathogenic molecular mechanisms, which provide an important basis for the molecular diagnosis of the disease as well as for assisted reproductive technology.
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Espermatozoides/patologia , Teratozoospermia/genética , Proteínas do Citoesqueleto , Humanos , Masculino , Proteínas de Membrana , Mutação , Proteínas NuclearesRESUMO
BACKGROUND/AIMS: Systemic iron homeostasis is strictly governed in mammals; however, disordered iron metabolism (such as excess iron burden) is recognized as a risk factor for various types of diseases including AS (Atherosclerosis). The hepcidin-ferroportin axis plays the key role in regulation of iron homeostasis and modulation of this signaling could be a potential therapeutic strategy in the treatment of these diseases. TMP (Tetramethylpyrazine) has been reported to have therapeutical effect on AS. Here, we aimed to investigate the effect of iron overload under hyperlipidemia condition on the endothelial injury, inflammation and oxidative stress by employing FPN1 Tek-cre mouse model with or without TMP intervention. METHODS: Subjects for this study were 80 FPN1 Tek-cre mice and 40 C57BL/6 mice and we randomly divided them into six groups: Group N: C57BL/6 mice with normal diet, Group M: C57BL/6 mice with high-fat diet, Group FN: FPN1 Tek-cre mice with normal diet, Group FNT: FPN1 Tek-cre mice with normal diet and TMP injection, Group FM: FPN1 Tek-cre mice with high-fat diet, Group FMT: FPN1 Tek-cre mice with high-fat diet and TMP injection. After seven days of treatment, blood samples were obtained to detect the levels of blood lipids, Hepcidin, NO, ET-1, ROS, MDA, SOD, IL-1, IL-6 and TNF-α respectively. The liver and aorta were used for testing the lipid deposition by using hematoxylin and eosin(HE). RESULTS: Hyperlipidemia could cause iron overload in the aorta and increased serum hepcidin level, particularly in FPN1 Tek-cre mice, and can be reversed by TMP intervention. Knockout of Fpn1 induced increase of serum hepcidin, exacerbated endothelial dysfunction, oxidative stress and inflammatory response, particularly under hyperlipidemia condition. TMP intervention attenuated these processes. CONCLUSIONS: Our study signifies the potential application of certain natural compounds to ameliorating iron disorders induced by hyperlipidemia and protecting on endothelial function through modulation of hepcidin-ferroportin signaling.
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Antioxidantes/uso terapêutico , Proteínas de Transporte de Cátions/metabolismo , Células Endoteliais/efeitos dos fármacos , Hiperlipidemias/complicações , Sobrecarga de Ferro/tratamento farmacológico , Sobrecarga de Ferro/etiologia , Pirazinas/uso terapêutico , Animais , Aorta/efeitos dos fármacos , Aorta/metabolismo , Aorta/patologia , Medicamentos de Ervas Chinesas/uso terapêutico , Células Endoteliais/metabolismo , Feminino , Hepcidinas/sangue , Hepcidinas/metabolismo , Hiperlipidemias/metabolismo , Hiperlipidemias/patologia , Sobrecarga de Ferro/metabolismo , Sobrecarga de Ferro/patologia , Masculino , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacosRESUMO
CONTEXT: Wenshen Yangxue decoction (WSYXD) is a famous traditional Chinese medicine (TCM) formula and has been used in infertility treatment, but the exact mechanism is still unknown. OBJECTIVES: To determine if WSYXD improves endometrial receptivity recovery and promotes endometrial angiogenesis in a rat model. MATERIALS AND METHODS: A total of 100 proestrus female SPF Wistar rats were randomly assigned into five groups: control (saline), model (saline and hydroxyurea solution), high (5.2/100 g), middle (2.6/100 g) and low (1.3/100 g) WSYXD dose groups for 10 d. The microvessel densities, endometrial microstructure, as well as blastocysts number, were observed, followed by detection of angiogenesis-related gene/protein expression by immunohistochemistry, western blot and quantitative real-time polymerase chain reaction (RT-PCR), respectively. RESULTS: Compared with the model group, the blastocyst number in WSYXD middle and high groups were significantly increased (4.50 ± 3.11 vs. 13.00 ± 2.12, 14.00 ± 1.83, p < 0.01). Lower MVD can be found in the model group (4.7) when compared with the normal control (13.7), middle (8.4) and high (9.7) dose groups. Additionally, significant differences were observed in VEGF, HIF-1α, p-AKT, p-PI3K, Ang1 and Ang2 (all p < 0.01) among different groups. DISCUSSION AND CONCLUSIONS: In conclusion, WSYXD could help endometrial receptivity recovery and promote endometrial angiogenesis through PI3K, HIF-1α signalling and VEGF expression regulation. This study provides molecular evidence for application of WSYXD in the clinic and promotes new drug development from TCM.
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Medicamentos de Ervas Chinesas/farmacologia , Endométrio/efeitos dos fármacos , Modelos Animais , Neovascularização Fisiológica/efeitos dos fármacos , Recuperação de Função Fisiológica/efeitos dos fármacos , Animais , Medicamentos de Ervas Chinesas/isolamento & purificação , Endométrio/patologia , Endométrio/fisiologia , Feminino , Neovascularização Fisiológica/fisiologia , Distribuição Aleatória , Ratos , Ratos Wistar , Recuperação de Função Fisiológica/fisiologiaRESUMO
Objective To observe the correlation between blood glucose fluctuation in type 2 dia- betes mellitus ( T2DM) patients and vascular endothelial injury/platelet activation/protein kinase Cß1 (PKCpß1). Methods Capillary blood was collected from finger tips of 38 T2DM patients at 7 time points, i.e., before 3 meals, 2 h after 3 meals, 21:00 pm before sleep. The mean amplitude of plasma glucose excursions (MAGE) was calculated. The peripheral blood platelet aggregation rate (PAG) induced by a- denosine diphosphate (ADP) and platelet membrane protein level of CD62p were determined by platelet fluorescent aggregometer and flow cytometry respectively. HbAlc was measured by ion-exchange high- performance liquid chromatography. Serum levels of E-selectin, von Willebrand factor ( vWF), and PKCß1 were detected by ELISA. Meanwhile, liver and renal functions, blood lipids were also measured. Their blood pressure was measured and body mass index (BMI) calculated. By taking HbA1c as a moni- tored index for assessing long-term glucose control, MAGE as an indicator for assessing glucose fluctua- tion, the correlations between serum markers for vascular endothelial injury (levels of E-selectin and vWF)/platelet activation indices (PAG and CD62p expression) and PKCß1 level/MAGE respectively were analyzed using Pearson correlation analysis and multivariant Logistic regression. The correlations be- tween PKCß1 level and MAGE/HbA1 c were also analyzed. Results In simple correlation analysis, there were no significant correlations between age/BMI/course of disease/medical history/serum levels of E-se- lectin/vWF/PKCß1/PAG/CD62p expression and MAGE (P >0. 05). There were significant correlations be- tween vascular endothelial injury markers ( E-selectin and vWF)/platelet activation indicators ( PAG, CD62p expression) and MAGE (r =0. 468, 0. 609, 0. 451 , 0. 674; P <0. 01). There were significant corre- lations between PKCß1 and glucose assessment indicators (MAGE and HbA1c)/vascular endothelial inju- ry markers ( E-selectin and vWF) , platelet activation indicators ( PAG and CD62p expression) (r = 0. 643, 0. 705, 0. 394, 0. 665, 0. 441 , 0. 577; P <0. 01). Conclusion PKCß1 , the key regulatory gene of coronary artery disease with blood stasis syndrome, was closely related with the degree of vascular en- dothelial injury and aggregation level of platelet activation in T2DM patients with blood glucose fluctuation.
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Glicemia , Diabetes Mellitus Tipo 2 , Ativação Plaquetária , Agregação Plaquetária , Biomarcadores , Plaquetas , Diabetes Mellitus Tipo 2/fisiopatologia , Humanos , Selectina-P , Fator de von WillebrandRESUMO
Ginsenoside Rb3 (GRb3) is one of the main components in plasma of Panax quinquefolius Saponin of stem and leaf (PQS), which can be into human plasma. Previous studies have found PQS has estrogen-like vascular protective effects. In the present study, we investigated the estrogen-like protective effect of GRb3 on oxidative stress and dysfunction of endothelial cells induced by oxidized low-density lipoprotein. The activities of SOD, NOS and the contents of MDA in the cell lysate were examined by enzyme method or spectrophotometry. The NO and ET-1 concentrations in the cell culture supernatant were measured by ELISA method. The iNOS and eNOS mRNA expression were measured by real time RT-PCR, while the phosphorylation levels of Akt was measured by Western blotting. The results showed that GRb3 could enhance the activity of SOD, reduce the content of MDA, increase the level of NOS, NO, ET-1 and iNOS mRNA expression while decrease the eNOS mRNA expression and the phosphorylation level of Akt. These effects were blocked by estrogen receptor antagonist ICI182780. GRb3 can play a role in protecting vascular endothelial cells by estrogen receptors, the protective mechanism is similar to 17-ß estrodiol.
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Células Endoteliais/efeitos dos fármacos , Ginsenosídeos/farmacologia , Lipoproteínas LDL/efeitos adversos , Estresse Oxidativo , Células Cultivadas , Endotelina-1/metabolismo , Estradiol/análogos & derivados , Estrogênios/farmacologia , Fulvestranto , Humanos , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Panax/química , Fosforilação , Saponinas/farmacologia , Superóxido Dismutase/metabolismoRESUMO
Background: Stroke is a devastating global health issue, with high mortality and disability rates. The increasing prevalence of male infertility among reproductive-aged men has become a growing concern worldwide. However, the relationship between male infertility and stroke incidence remains uncertain. This study aimed to address this knowledge gap by employing a Mendelian randomization (MR) approach. Method: Utilizing genetic instrumental variables derived from a genome-wide association study (GWAS) on male infertility and stroke, a two-sample MR design was implemented. Five different analysis methods, with inverse-variance weighted as the primary approach, were used to examine the genetic causal associations between male infertility and various stroke subtypes. Heterogeneity analysis, pleiotropy tests, and leave-one-out validation were conducted to assess heterogeneity, evaluate pleiotropy, and ensure the robustness of the findings. Result: The results indicate a potential lower risk of small vessel stroke associated with male infertility (odds ratio, 95% confidence interval: 0.82, 0.68 to 0.99, p=0.044), although no significant impact on other stroke subtypes was observed. The study exhibited low heterogeneity and no apparent pleiotropy; however, the stability of the results was not optimal. Conclusion: Male infertility might potentially confer a protective effect against small vessel stroke risk. Caution is warranted due to potential confounding factors. Additional studies are necessary to confirm these findings and provide further validation.
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Estudo de Associação Genômica Ampla , Infertilidade Masculina , Análise da Randomização Mendeliana , Acidente Vascular Cerebral , Humanos , Masculino , Infertilidade Masculina/genética , Infertilidade Masculina/epidemiologia , Acidente Vascular Cerebral/genética , Acidente Vascular Cerebral/epidemiologia , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Predisposição Genética para DoençaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Semen Cuscutae and Fructus Lycii (SC-FL) is a commonly used herbal pair for male infertility treatment. Studies have found that the mechanism of SC-FL treatment may be related to repairing the blood-testis barrier (BTB). The application of network pharmacology can be used to explore the correlation between medicines and diseases and predict the potential pharmacological mechanisms of SC-FL. AIM OF THE STUDY: This study aimed to explore the specific effects and mechanisms of SC-FL in repairing the BTB and initially revealed the mechanism of Chinese medicine treating male infertility through network pharmacology and animal experiments. MATERIALS AND METHODS: We searched databases using the network pharmacology method and performed mass spectrometry analysis. We analyzed and predicted the active ingredients, targets and key pathways of SC-FL in male infertility treatment. Then, we designed animal experiments to verify the results. Thirty-six Sprague-Dawley rats were randomly divided into the normal control group (NC group), spermatogenic dysfunction group (SD group) and SC-FL treatment group (SCFL group). Glucosides of Tripterygium wilfordii Hook. F (GTW) (40 mg/kg/d) was administered for 4 weeks to generate a spermatogenic dysfunction model. The rats in the SCFL group were given the SC-FL suspension (6 g/kg/d) daily. After 4 weeks of treatment, we detected the sperm quality of each group of rats and observed the cell morphology. Western blotting and qRT-PCR were used to detect the expression of BTB-related proteins in testicular tissues. RESULTS: 213 chemical ingredients of SC and FL were retrieved from the TCMSP database, and 54 effective chemical ingredients were obtained. Mass spectrometry analysis showed the above results were credible. Then, we identified 44 potential targets for the treatment of male infertility, and we plotted a network diagram of the interaction network between the core targets and a diagram of herbal medicine-active ingredient-target-disease interactions. The target genes were enriched according to biological functions, and 22 biological processes, 49 cellular components, 1487 molecular functions, and 122 signaling pathways were obtained. The results of the animal experiments showed that the sperm concentration and motility of the SCFL group were significantly improved compared with those of the SD group. Compared with those in the SD group, the structure and morphology of the Sertoli cells and seminiferous tubules of rats in the SCFL group improved, and the number of spermatogenic cells increased significantly. Western blotting and qRT-PCR results showed that compared with that in the SD group, the expression of p38 MAPK decreased significantly, and the expression of c-Jun, Occludin, ZO-1 and connexin 43 increased significantly in the SCFL group. CONCLUSION: We predicted that the active ingredients of SC-FL can treat male infertility by interacting with the core targets JUN, IL6, MAPK1, TP53, MYC, CCND1, AR, EGF, FOS, and MAPK8, and the possible mechanism is related to the MAPK signaling pathway. SC-FL can regulate the MAPK pathway and affect the expression of Occludin, ZO-1 and connexin 43 to repair damaged BTB and improve spermatogenic dysfunction induced by GTW, which may be one of the possible mechanisms.
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Barreira Hematotesticular/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Infertilidade Masculina/tratamento farmacológico , Espermatogênese/efeitos dos fármacos , Testículo , Tripterygium/química , Animais , Caderinas/genética , Caderinas/metabolismo , Simulação por Computador , Conexina 43/genética , Conexina 43/metabolismo , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/uso terapêutico , Regulação da Expressão Gênica/efeitos dos fármacos , Genes jun/efeitos dos fármacos , Glucosídeos/toxicidade , Técnicas In Vitro , Infertilidade Masculina/induzido quimicamente , Masculino , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Ocludina/genética , Ocludina/metabolismo , Mapas de Interação de Proteínas/efeitos dos fármacos , Ratos Sprague-Dawley , Contagem de Espermatozoides , Motilidade dos Espermatozoides/efeitos dos fármacos , Testículo/efeitos dos fármacos , Testículo/metabolismo , Testículo/patologia , Testículo/ultraestrutura , Proteína da Zônula de Oclusão-1/genética , Proteína da Zônula de Oclusão-1/metabolismo , beta Catenina/genética , beta Catenina/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
Glycemic variability (GV) plays an important role in the pathogenesis of vascular complications associated with diabetes mellitus (DM). Paeoniflorin is an effective Chinese traditional medicine with anti-inflammatory and immune-regulatory effects. Previous studies implicated the beneficial effects of paeoniflorin in treatment for diabetic complications, such as type 2 diabetic nephropathy and diabetes with myocardial ischemic injury. Current evidence suggests that oxidative stress and platelet activation, as well as their interaction, are potentially associated with GV and involved in the pathogenesis of diabetes-associated vascular complications. This study aimed to explore the effects of paeoniflorin on oxidative stress and platelet activation, using human umbilical vein endothelial cells (HUVECs) cultured with different glucose concentrations, and streptozotocin-induced diabetic rats fed different glycemic index diets. Paeoniflorin treatment effectively improved the morphology and cell viability of HUVECs under glucose fluctuation. Moreover, the platelet aggregation rate, CD62p expression, and reactive oxygen species (ROS) concentration decreased, while glutathione peroxidase (GSH-px) levels increased in paeoniflorin-treated groups. In conclusion, our study found that paeoniflorin ameliorates oxidative stress and platelet activation induced by glycemic variability both in vivo and in vitro, suggesting a novel potential strategy for treatment of diabetic complications.
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ETHNOPHARMACOLOGICAL RELEVANCE: Semen Cuscutae is the seed of Cuscuta japonica Choisy, and Fructus Lycii is the mature fruit of Lycium barbarum L. (Solanaceae). Semen Cuscutae and Fructus Lycii (SC-FL) are well-known Chinese medicine which have been used to tonify the kidney and replenish the essence for thousands of years. Chinese physicians prefer to prescribe them for treating male infertility. Recent studies have found that SC-FL repair spermatogenic dysfunction, however, the therapeutic mechanism has yet to be clearly elucidated. AIM OF THE STUDY: This study aimed at evaluating the therapeutic effect of SC-FL in glucosides of Tripterygium wilfordii Hook. f (GTW)-induced dyszoospermia rats and elucidating the underlying molecular mechanism. MATERIALS AND METHODS: Seventy-eight Sprague-Dauley (SD) rats were randomly divided into five groups: normal control (treated with saline), GTW (treated with saline), GTW + levocarnitine (treated with levocarnitine), GTW + SCFL (treated with SC-FL), and LY (LY294002, the PI3K inhibitor) +SCFL (treated with SC-FL). GTW (40 mg/kg/d) was intragastrically administered for 4 weeks to establish dyszoospermia model. From the start of the study, LY was additionally injected into the tail vein of rats of the LY + SCFL group once a week. After 8 weeks, semen quality and organ coefficient were determined and sex hormone, inhibin B, and epididymal carnitine levels were measured. Testicular tissue and its ultrastructure were observed using H&E (hematoxylin-eosin) staining and electron microscopy. Immunohistochemistry, western blotting, and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were used to determine the protein and mRNA expression of SCF, c-kit, PI3K, p-Akt, Bad, Bcl-2, and Bax in rat testis. RESULTS: Compared with the GTW group, semen quality, the organ coefficient, follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), and epididymal carnitine levels were significantly improved in the GTW + SCFL group (P < 0.05 or P < 0.01). Histomorphology and testicular ultrastructural evaluation showed that in the GTW + SCFL group, the structure and arrangement of seminiferous tubules were better, the amount of spermatogenic cells increased significantly, the morphology of spermatogenic cells improved, and the mitochondria increased, compared to those in the GTW group. Immunohistochemistry, western blotting, and qRT-PCR results showed that compared with the GTW group, the expression of SCF, c-kit, PI3K, p-Akt, and Bcl-2 in the GTW + SCFL group was increased, while that of Bax and Bad was decreased. The expression of p-Akt and Bcl-2 decreased, while that of Bad and Bax increased in the LY + SCFL group compared with the SCFL group. CONCLUSION: SC-FL can effectively inhibit spermatogenic cell apoptosis and promote their proliferation, and the mechanism may be related to the regulation of the SCF/c-kit--PI3K--Bcl-2 pathway.
Assuntos
Cuscuta , Frutas , Glucosídeos , Lycium , Sementes , Espermatozoides/efeitos dos fármacos , Tripterygium , Animais , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Hormônios Esteroides Gonadais/sangue , Masculino , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-kit/genética , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Espermatogênese/efeitos dos fármacos , Fator de Células-Tronco/genética , Testículo/efeitos dos fármacos , Testículo/metabolismoRESUMO
BACKGROUND: Premature ejaculation (PE) is one of the most common male sexual dysfunctions, which can directly harm men's self-esteem and affect the stability of the relationship between husband and wife. To some extent, PE even affects the harmony and stability of society. So, men's health has gained more and more attention. As one of the long-acting selective serotonin reuptake inhibitors (SSRIs), fluoxetine has been proven to be effective in the treatment of PE by many trails. In this study, we aim to evaluate the effectiveness and safety of fluoxetine for PE to provide the newest evidence for clinical use. METHODS AND ANALYSIS: Literature research will be divided into 2 parts: electronic search and manual search. We will search PubMed, EMBASE, The Cochrane Library, the China National Knowledge Infrastructure (CNKI), China Biology Medicine disc (CBMdisc), the China Science and Technology Journal database (VIP), and the Wanfang database online. We will select the eligible studies published up to December 31, 2018. Manual searches mainly retrieve dissertations, ongoing trails, internal reports, and so on. We use intravaginal ejaculatory latency time (IELT) as the primary outcome of PE and we also care about the following indexes: PE Diagnostic Tool (PEDT); Arabic index of PE (AIPE); Index of PE (IPE). In addition, we will carefully observe the patient's adverse reactions during the medication. Two reviewers will read the articles, extract the data information, and assess the risk of bias independently. Data analysis will be used the software such as RevMan V.5.3.5; EndNote X7 and Stata 13.0. RESULTS: This study will provide a high-quality synthesis of current evidence of fluoxetine for PE from several aspects, including IELT, PEDT, AIPE, IPE, and adverse events. CONCLUSION: This systematic review will provide evidence to assess the effectiveness and safety of fluoxetine in the treatment of PE. TRIAL REGISTRATION NUMBER: PROSPERO CRD42018109722.
Assuntos
Fluoxetina/uso terapêutico , Ejaculação Precoce/tratamento farmacológico , Projetos de Pesquisa , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , China , Humanos , Masculino , Saúde do Homem , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Iron homeostasis is strictly regulated in mammals, and disordered iron metabolism is recognized as a risk factor for various diseases, including cardiovascular disease. The hepcidinferroportin axis is the key signaling mechanism that controls systemic iron homeostasis. Increased serum hepcidin is associated with multiple types of cancer and atherosclerosis (AS), and therapeutics that decrease hepcidin levels have been proposed to treat these diseases. However, the effects of abnormal circulating hepcidin on hyperlipidemia remain unexploited. The natural compound tetramethylpyrazine (TMP) has been reported to have therapeutic effects on cardiovascular diseases, whereas the mechanisms involved remain incompletely understood. Thus, the effects of TMP on the expression of hepcidin in hyperlipidemic mice were investigated and the mechanisms involved were explored. Hyperlipidemia increased serum hepcidin, which was inhibited by TMP intervention. The results also indicated that TMP may decrease hepcidin expression via inhibition of Stat3 signaling. These findings suggest a promising rationale to prevent and hyperlidemia by targeting hepcidin or its upstream regulators, and highlight the potential application of natural compounds in treating hepcidin disorderassociated diseases.
Assuntos
Hepcidinas/metabolismo , Homeostase , Hiperlipidemias/patologia , Pirazinas/farmacologia , Animais , Feminino , Hepcidinas/sangue , Homeostase/efeitos dos fármacos , Hiperlipidemias/sangue , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipídeos/sangue , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos Endogâmicos C57BL , Modelos Biológicos , Fosforilação/efeitos dos fármacos , Fator de Transcrição STAT3/metabolismoRESUMO
BACKGROUND: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common urinary system disease in the male population. Recent studies have shown that acupuncture can alleviate the pain caused by CP/CPPS to a certain extent and improve the quality of life of patients. This study used a network meta-analysis (NMA) to compare the effectiveness and safety of different forms of acupuncture on CP/CPPS. METHODS AND ANALYSIS: We will search for PubMed, Cochrane Library, AMED, EMbase, WorldSciNet; Nature, Science online and China Journal Full-text Database, China Biomedical Literature CD-ROM Database, and related randomized controlled trials (RCTs) included in the China Resources Database. The time is limited from the construction of the library to December 2018. The quality of the included RCTs will be evaluated with the risk of bias tool and evidence will be evaluated by grading of recommendations assessment, development, and evaluation. STATA 13.0 and WinBUGS 1.4.3 through the GeMTC package will be used to perform a NMA to synthesize direct and indirect evidence. RESULTS: The results of this NMA will be submitted to a peer-reviewed journal for publication. TRIAL REGISTRATION NUMBER: PROSPERO CRD42018111408.