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Basal-like breast cancer (BLBC) is the most malignant subtype of breast cancer because of its aggressive clinical behaviour and lack of effective targeted agents. Krüppel-like factor 5 (KLF5) is an oncogenic transcription factor that is highly expressed in BLBC. The deubiquitinase (DUB) BRCA1-associated protein 1 (BAP1) stabilizes KLF5 and promotes BLBC growth and metastasis. Therefore, pharmacological inhibition of the BAP1âKLF5 axis is an effective therapeutic strategy for BLBC. Here, through screening, we identified a series of tetrahydro-ß-carboline derivatives that effectively reduced the protein expression of KLF5 and exhibited strong antitumour activity. Among the investigated compounds, the lead compound LN-439A presented the strongest antitumour activity and inhibitory effect on KLF5 expression. LN-439A suppressed the proliferation and migration of BLBC cells, induced G2/M arrest, and induced apoptosis. Mechanistically, LN-439A functions as a small molecule catalytic inhibitor of BAP1 by binding to the catalytic pocket of BAP1, leading to the ubiquitination and degradation of KLF5. Consistent with this finding, the overexpression of KLF5 suppressed the antitumour effects of LN-439A. In summary, LN-439A is a promising therapeutic agent for BLBC that functions by targeting the BAP1âKLF5 axis.
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Many G-protein-coupled receptor (GPCR) agonists have been studied for transactivating epidermal growth factor receptor (EGFR) signaling through extracellular or intracellular pathways. Accumulated evidence has confirmed that GPCR transactivation participates in various diseases. However, the clinical application of GPCR transactivation has not been explored, and more translational studies are needed to develop therapies to target GPCR-mediated EGFR transactivation. In cancer patients treated with EGFR inhibitors (EGFRi), especially afatinib, a unique acneiform rash is frequently developed. In this study, we first established the connection between GPCR transactivation and EGFRi-induced skin disease. We examined the ability of three different GPCR agonists to reverse signaling inhibition and ameliorate rash induced by EGFRi. The activation of different agonists follows unique time and kinase patterns. Rats treated with EGFRi show a similar skin phenotype, with rash occurring in the clinic; correspondingly, treatment with GPCR agonists reduced keratinocyte apoptosis, growth retardation and infiltration of inflammatory cytokines by transactivation. This phenomenon demonstrates that EGFR inhibition in keratinocytes regulates key factors associated with rash. Our findings indicate that maintaining EGFR signaling by GPCR agonists might provide a possible therapy for EGFR inhibitor-induced skin toxicities. Our study provides the first example of the translational application of GPCR transactivation in treating diseases.
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Exantema , Dermatopatias , Afatinib , Animais , Receptores ErbB , Humanos , Inibidores de Proteínas Quinases , Ratos , Receptores Acoplados a Proteínas G/metabolismo , Ativação TranscricionalRESUMO
A mild and efficient method catalyzed by α-chymotrypsin was developed for the synthesis of bis(indolyl)methanes through a cascade process between indole and aromatic aldehydes. In the ethanol aqueous solution, a green medium, a wide range of aromatic aldehydes could react with indole to afford the desired products with moderate to good yields (from 68% to 95%) using a little α-chymotrypsin as catalyst.
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Biocatálise , Química Orgânica/métodos , Quimotripsina/metabolismo , Indóis/síntese química , Metano/síntese química , Animais , Bovinos , Etanol/química , Indóis/química , Metano/química , Sus scrofa , TemperaturaRESUMO
Objective: There are variabilities in the distance between the tibial tuberosity and the trochlear groove. The knee angle needs to be considered when talking about patellofemoral instability. Methods: This retrospective study analyses the MRI images of knee angles from 0 and 30 degrees in the patella dislocation group (20 cases) and in the control group (20 cases) from Dec 2017 to Dec 2019. Two experienced orthopedic physicians separately measure the study with a blind experiment method. Results: The TT-TG data of the patella dislocation group and control group are 17.88 ± 3.40 mm and 13.31 ± 3.01 mm when the knee angle is 0, which indicates a difference with statistical significance (P < 0.01). The TT-TG data of the patella dislocation group and control group are 11.51 ± 3.60 mm and 7.40 ± 1.93 mm when the knee angle is at 30 degrees, indicating a statistically significant difference (P < 0.01). Also, the TT-TG data of both the patella dislocation group and control group have statistically significant differences within different knee angles of the same group (P < 0.01). The differences of TT-TG are 6.36 ± 2.43 mm and 5.92 ± 1.65 mm when the knee angle changes from 0 to 30, which shows no statistically significant difference (P > 0.01). Conclusion: This research initially obtained the relevant MRI data of the TT-TG distance from different knee angles between the Chinese patella dislocation patient group and control group. The study received a new criterion to evaluate the TT-TG of patients with patella dislocations when the knee angle is below 30 degrees. The knee flexion angles need to be considered to measure the TT-TG distance when comprehensively evaluating patellofemoral instability. The TT-TG distance gradually increases when the knee changes from flexion to extension. The difference of the TT-TG distances shows no statistically significant difference.
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Background: Tumor immune microenvironment (TIM) plays a critical role in tumorigenesis and progression. Recently, therapies based on modulating TIM have made great breakthroughs in cancer treatment. Polo-like kinase 1 (PLK1) is a crucial regulatory factor of the cell cycle process and its dysregulations often cause various pathological processes including tumorigenesis. However, the detailed mechanisms surrounding the regulation of PLK1 on glioma immune microenvironment remain undefined. Methods: Public databases and online datasets were used to extract data of PLK1 expression, clinical features, genetic alterations, and biological functions. The EdU, flow cytometry, and macrophage infiltration assays as well as xenograft animal experiments were performed to determine the relationship between PLK1 and glioma immune microenvironment in vivo and in vitro. Results: PLK1 is always highly expressed in multiple cancers especially in glioma. Univariable and Multivariate proportional hazard Cox analysis showed that PLK1 was a prognostic biomarker for glioma. Simultaneously, highly expressed PLK1 is significantly related to prognosis, histological and genetic features in glioma by analyzing public databases. In addition, the enrichment analysis suggested that PLK1 might related to "immune response", "cell cycle", "DNA replication", and "mismatch repair" in glioma. Immune infiltration analysis demonstrated that highly expressed PLK1 inhibited M1 macrophages infiltration to glioblastoma immune microenvironment by Quantiseq and Xcell databases and negatively related to some chemokines and marker genes of M1 macrophages in glioblastoma. Subsequent experiments confirmed that PLK1 knockdown inhibited the proliferation of glioma cells but increased the M1 macrophages infiltration and polarization. Furthermore, in glioma xenograft mouse models, we showed that inhibiting PLK1 blocked tumor proliferation and increased the M1 macrophages infiltration. Finally, PLK1 methylation analysis and lncRNA-miRNA network revealed the potential mechanism of abnormal PLK1 expression in glioma. Conclusions: PLK1 inhibits M1 macrophages infiltration into glioma immune microenvironment and is a potential biomarker for glioma.
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Glioblastoma , Glioma , Humanos , Animais , Camundongos , Glioblastoma/patologia , Glioma/patologia , Macrófagos , Carcinogênese/metabolismo , Microambiente Tumoral , Quinase 1 Polo-LikeRESUMO
Bacillus amyloliquefaciens strain EA19 is an endophyte isolated from Erigeron annuus with antifungal activity against Blumeria graminis f. sp. tritici, Magnaporthe oryzae, and Fusarium graminearum. The genome sequence of this strain is 3.96 Mb and contains 3,421 coding sequences, which will facilitate an understanding of the mechanisms of biocontrol.
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BACKGROUND: Pseudomyxoma peritonei (PMP) is a clinical malignant syndrome mainly originating from the appendix, with an incidence of 2-4 per million people. As a rare disease, an early and accurate diagnosis of PMP is difficult. It was not until the 1980s that the systematic study of this disease was started. MAIN BODY: As a result of clinical and basic research progress over the last 4 decades, a comprehensive strategy based on cytoreductive surgery (CRS) + hyperthermic intraperitoneal chemotherapy (HIPEC) has been established and proved to be an effective treatment for PMP. Currently, CRS + HIPEC was recommended as the standard treatment for PMP worldwide. There are several consensuses on PMP management, playing an important role in the standardization of CRS + HIPEC. However, controversies exist among consensuses published worldwide. A systematic evaluation of PMP consensuses helps not only to standardize PMP treatment but also to identify existing controversies and point to possible solutions in the future. The controversy underlying the consensus and vice versa promotes the continuous refinement and updating of consensuses and continue to improve PMP management through a gradual and continuous process. In this traditional narrative review, we systemically evaluated the consensuses published by major national and international academic organizations, aiming to get a timely update on the treatment strategies of CRS + HIPEC on PMP. CONCLUSION: Currently, consensuses have been reached on the following aspects: pathological classification, terminology, preoperative evaluation, eligibility for surgical treatment, maximal tumor debulking, CRS technical details, and severe adverse event classification system. However, controversies still exist regarding the HIPEC regimen, systemic chemotherapy, and early postoperative intraperitoneal chemotherapy.
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Hipertermia Induzida , Neoplasias Peritoneais , Pseudomixoma Peritoneal , Consenso , Procedimentos Cirúrgicos de Citorredução , Humanos , Neoplasias Peritoneais/terapia , Pseudomixoma Peritoneal/diagnóstico , Pseudomixoma Peritoneal/cirurgiaRESUMO
Polarization is one of the inherent characteristics. Because the surface of the target structure, internal structure, and the angle of incident light are different, the earth's surface and any target in atmosphere under optical interaction process will have their own characteristic nature of polarization. Polarimetric characteristics of radiation energy from the targets are used in polarization remote sensing detection as detective information. Polarization remote sensing detection can get the seven-dimensional information of targets in complicated backgrounds, detect well-resolved outline of targets and low-reflectance region of objectives, and resolve the problems of atmospheric detection and identification camouflage detection which the traditional remote sensing detection can not solve, having good foreground in applications. This paper introduces the development of polarization information in the remote sensing detection from the following four aspects. The rationale of polarization remote sensing detection is the base of polarization remote sensing detection, so it is firstly introduced. Secondly, the present researches on equipments that are used in polarization remote sensing detection are particularly and completely expatiated. Thirdly, the present exploration of theoretical simulation of polarization remote sensing detection is well detailed. Finally, the authors present the applications research home and abroad of the polarization remote sensing detection technique in the fields of remote sensing, atmospheric sounding, sea surface and underwater detection, biology and medical diagnosis, astronomical observation and military, summing up the current problems in polarization remote sensing detection. The development trend of polarization remote sensing detection technology in the future is pointed out in order to provide a reference for similar studies.
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The rapid development of online social networks not only enables prompt and convenient dissemination of desirable information but also incurs fast and wide propagation of undesirable information. A common way to control the spread of pollutants is to block some nodes, but such a strategy may affect the service quality of a social network and leads to a high control cost if too many nodes are blocked. This paper considers the node selection problem as a biobjective optimization problem to find a subset of nodes to be blocked so that the effect of the control is maximized while the cost of the control is minimized. To solve this problem, we design an ant colony optimization algorithm with an adaptive dimension size selection under the multiobjective evolutionary algorithm framework based on decomposition (MOEA/D-ADACO). The proposed algorithm divides the biobjective problem into a set of single-objective subproblems and each ant takes charge of optimizing one subproblem. Moreover, two types of pheromone and heuristic information are incorporated into MOEA/D-ADACO, that is, pheromone and heuristic information of dimension size selection and that of node selection. While constructing solutions, the ants first determine the dimension size according to the former type of pheromone and heuristic information. Then, the ants select a specific number of nodes to build solutions according to the latter type of pheromone and heuristic information. Experiments conducted on a set of real-world online social networks confirm that the proposed biobjective optimization model and the developed MOEA/D-ADACO are promising for the pollutant spreading control.
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Disseminação de Informação , Modelos Biológicos , Rede Social , Algoritmos , Heurística Computacional , Poluentes Ambientais , Internet , Modelos Estatísticos , FeromôniosRESUMO
OBJECTIVE: Recent studies have shown that Chondroitin polymerizing factor (CHPF) is abnormally expressed in malignant tumors, however, the expression of CHPF in lung adenocarcinoma (LUAD) has not been reported. In this study, the relationship of CHPF and LUAD will be explored. METHODS: Differential genes present in LUAD were screened by bioinformatics analysis. The expression status of CHPF in LUAD tissues and cell lines were deteced by Western blotting or Real-time Quantitative Polymerase Chain Reaction Detecting System (qPCR), and the relationship between CHPF and prognosis of LUAD patients was analyzed. CHPF was effectively silenced in LUAD cell lines by lentivirus- mediated methods. The effect of CHPF on proliferation, cell cycle progression and apoptosis of cancer cells was assessed. We further determined the role of CHPF in tumor growth in vivo by using xenograft LUAD tumor models. Western blotting assay was performed to assess the expression changes of MAPK signaling pathway. RESULTS: We found that CHPF is highly expressed in LUAD tissues and cell lines. In vitro experiments, CHPF knockdown in LUAD cells can effectively inhibit proliferation and promote apoptosis of cancer cell. In vivo experiment, tumor growth was markedly inhibited by CHPF knockdown in the xenograft model of LUAD. Notably, CHPF also could promote tumor progression by regulating MAPK pathway. CONCLUSION: CHPF can promote the proliferation and antiapoptosis of LUAD cells, which is promising to become a potential target for LUAD treatment.
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Adenocarcinoma de Pulmão/patologia , Neoplasias Pulmonares/patologia , Sistema de Sinalização das MAP Quinases/fisiologia , N-Acetilgalactosaminiltransferases/metabolismo , Adenocarcinoma de Pulmão/metabolismo , Adenocarcinoma de Pulmão/mortalidade , Adulto , Idoso , Animais , Apoptose/fisiologia , Biomarcadores Tumorais/análise , Proliferação de Células/fisiologia , Feminino , Xenoenxertos , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidade , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , PrognósticoRESUMO
OBJECTIVE: The tripartite motif 66(TRIM66) is an important member of the TRIM protein superfamily, which can participate in the expression of multiple proteins, and is closely associated with the behaviors of non-small cell lung cancer (NSCLC). In this study, we aimed to explore the effect of TRIM66 in this process in vitro using NSCLC cell lines, and the role of TRIM66 in regulating epithelial-mesenchymal transition(EMT) in NSCLC. METHODS: Western blotting was used to detect the TRIM66 protein expression levels in NSCLC cell lines and normal lung epithelial cells BEAS-2B. We silenced its expression in A549 cells by transient siRNA transfection to ascertain the function of TRIM66 in NSCLC cells. Western blotting was used to detect the expression of EMT-related proteins. RESULTS: TRIM66 protein content was highest in NSCLC cell line A549, compared with BEAS-2B, it showed that the TRIM66-siRNA group lung cancer cell proliferation was significantly reduced after knockdown of TRIM66, and knockdown of TRIM66 also suppressed invasion, migration and clonogenic ability of A549 cells. Finally, we found that siRNA-mediated TRIM66 silencing suppressed EMT by downregulating expression of N-cadherin and vimentin and upregulating that of E-cadherin in NSCLC cells, which could effectively reduce the invasive, migratory, and proliferative capacities of lung cancer cells. CONCLUSION: Silence TRIM66 expression suppressed NSCLC cell proliferation, invasion, and migration. The siRNA-mediated TRIM66 silencing could block the occurrence of EMT. TRIM66 could be a promising novel target for future NSCLC treatments.
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Carcinoma Pulmonar de Células não Pequenas/patologia , Transição Epitelial-Mesenquimal/fisiologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Neoplasias Pulmonares/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Técnicas de Silenciamento de Genes , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genéticaRESUMO
Protease serine 8 (PRSS8), a serine peptidase, has a widespread expression in normal epidermal cells. Recently, many researchers demonstrated downregulation of PRSS8 in cancer tissues as well as its tumor suppressor role in cancer development. However, the biological functions of PRSS8 in glioma remain unclear. In the current study, we demonstrated a decreased expression of PRSS8 in glioma tissues and cell lines. PRSS8 upregulation inhibited glioma cell proliferation, migration, and invasion. In addition, xenograft experiments showed that PRSS8 overexpression suppressed glioma cell growth in vivo. We also found that upregulated PRSS8 reduced the protein expression levels of p-Akt and p-mTOR in glioma cells. Taken together, our study demonstrated that overexpression of PRSS8 inhibited glioma cell proliferation, migration, and invasion via suppressing the Akt/mTOR signaling pathway. Therefore, PRSS8 may act as a novel therapeutic target for glioma.
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Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Glioma/genética , Glioma/patologia , Serina Endopeptidases/genética , Animais , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação para Baixo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos Endogâmicos BALB C , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina Endopeptidases/metabolismo , Transdução de Sinais/genética , Serina-Treonina Quinases TOR/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Conidia of the obligate biotrophic fungal pathogen Blumeria graminis f. sp. tritici (Bgt) play a vital role in its survival and rapid dispersal. However, little is known about the genetic basis for its asexual reproduction. To uncover the primary metabolic and regulatory events during conidiation, we sequenced the transcriptome of Bgt epiphytic structures at 3 (vegetative hyphae growth), 4 (foot cells initiation), and 5 (conidiophore erection) days post-inoculation (dpi). RNA-seq analyses identified 556 and 404 (combined 685) differentially expressed genes (DEGs) at 4 and 5 dpi compared with their expression levels at 3 dpi, respectively. We found that several genes involved in the conversion from a variety of sugars to glucose, glycolysis, the tricarboxylic acid cycle (TAC), the electron transport chain (ETC), and unsaturated fatty acid oxidation were activated during conidiation, suggesting that more energy supply is required during this process. Moreover, we found that glucose was converted into glycogen, which was accumulated in developing conidiophores, indicating that it could be the primary energy storage molecule in Bgt conidia. Clustering for the expression profiles of 91 regulatory genes showed that calcium (Ca2+), H2O2, and phosphoinositide (PIP) signaling were involved in Bgt conidiation. Furthermore, a strong accumulation of H2O2 in developing conidiophores was detected. Application of EGTA, a Ca2+ chelator, and trifluoperazine dihydrochloride (TFP), a calmodulin (CaM) antagonist, markedly suppressed the generation of H2O2, affected foot cell and conidiophore development and reduced conidia production significantly. These results suggest that Ca2+ and H2O2 signaling play important roles in conidiogenesis and a crosslink between them is present. In addition to some conidiation-related orthologs known in other fungi, such as the velvet complex components, we identified several other novel B. graminis-specific genes that have not been previously found to be implicated in fungal conidiation, reflecting a unique molecular mechanism underlying asexual development of cereal powdery mildews.
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After searching for literature about the specificity of acupoints from China National Knowledge Infrastructure (CNKI) database (in Chinese) and MEDLINE (in English), published by Chinese scholars from June 2003 to June 2012, the authors made a systemic analysis on the retrieved papers. It was found that most Chinese scholars took a positive viewpoint about the specificity of acupoints in morphological structure, biophysical characters, pathological reactions, acupuncture stimulation-induced responses in different brain regions and therapeutic effects. However, the research methods and comprehensive analysis of abundant research results need being improved, and the conclusion should be validated extensively. Moreover, the research on the affecting factors of specificity of acupoints will be one of the major directions.
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Pontos de Acupuntura , Meridianos , Terapia por Acupuntura , China , HumanosRESUMO
The contents of 2011 Tokyo Declaration on Japanese Acupuncture and Moxibustion (Declaration for short) and its effect on development situation, current status, features, opportunities and challenges of Japanese acupuncture and moxibustion are introduced, some proposals brought up in the Declaration are analyzed as well. The Declaration summarizes six characteristics of Japanese acupuncture and moxibustion, including paying great attention to palpation techniques such as pulse and abdominal diagnosis, always selecting response point in the meridian during acupuncture treatment, etc. Also six proposals have been brought up to promote the development of Japanese acupuncture and moxibustion, such as being devoted to spread the latest knowledge of acupuncture and moxibustion to medical professionals and the public in order to get correct understanding and proper evaluation, etc. What's more, the Declaration makes a prospection of improving international academic exchange and promoting the globalization of acupuncture and moxibustion and so on. The Declaration is served as a link between past and future in the history and developing process of Japanese acupuncture and moxibustion, which has a great meaning to the development of Japanese acupuncture and moxibustion. We should have a clear understanding of weakness and strength in the development of acupuncture and moxibustion, seize the opportunity and develop science of acupuncture and moxibustion with our own characteristics, which makes more contribution to development of international acupuncture and moxibustion.
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Terapia por Acupuntura/tendências , Moxibustão/tendências , Humanos , Japão , TóquioRESUMO
Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin (PRL) levels were examined during consecutive reproductive states in Mongolian gerbils. The results indicate that FSH, LH, and PRL levels peak at proestrus, estrus, and diestrus, respectively. During early gestation in primiparous gerbils, gonadotropin levels were the lowest on day 6. This was followed by an increase in FSH and LH levels until days 18 and 15, respectively, with levels remaining constant until day 21. However, in multiparous gerbils, gonadotropin levels were the lowest on day 12 of gestation and were relatively stable between days 15 to 21. In both primiparous and multiparous gerbils, gonadotropin levels increased rapidly from day 21 of gestation to day 3 of lactation, and kept stable between 6-24 days of lactation. PRL peaked during early gestation on days 9 and 6 in the primiparous and multiparous gerbils, respectively, followed by a decline. PRL levels subsequently peaked again on day 21 before parturition. During lactation, PRL levels peaked on days 6 and 9 in primiparous and multiparous gerbils, respectively, followed by a decline until lactation ended. These findings suggest that variations in gonadotropin during the estrous cycle, gestation, and lactation in Mongolian gerbils are similar to those observed in rats, whereas prolactin levels differ. Changes in gonadotropin and prolactin levels during different reproductive states were found to be similar in primiparous and multiparous gerbils, and were correlated with the reproductive stages of Mongolian gerbils.
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Ciclo Estral/sangue , Hormônio Foliculoestimulante/sangue , Gerbillinae/fisiologia , Lactação/sangue , Hormônio Luteinizante/sangue , Prenhez/sangue , Prolactina/sangue , Animais , Feminino , Gerbillinae/sangue , Camundongos , Paridade , Gravidez , RatosRESUMO
The contraceptive effects of quinestrol in Mongolian gerbils were examined. The results showed that body weight significantly increased after quinestrol treatment, except in the group that received the highest dose. The gonadosomatic index of ovaries decreased, whereas that of uteri increased, and uterine edema appeared after quinestrol treatment. Histological examination revealed that the ovaries had a lack of mature follicles and corpora lutea and that the myometrium and endometrium of the uteri became thin after quinestrol treatment. Persistent estrous appeared after quinestrol treatment, and time to persistent estrous shortened with increasing doses of quinestrol. Serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels decreased, whereas estradiol (E2) and progesterone (P4) levels increased after quinestrol treatment, and the effects were dose-dependent. During gestation, the serum E2 levels in the different treatment groups were not significantly different. During gestation in the control groups, the serum P4 levels from days 0 to 15 were higher than in the quinestrol-treated groups; however, they did not show significant differences from days 18 to 24. Doses of 0.1 to 2.7 µg/g quinestrol over 6 days completely inhibited fertility. Birth time was prolonged with increasing doses of quinestrol. The findings suggest that quinestrol has marked estrogenic effects in Mongolian gerbils and may inhibit follicle maturation and ovulation through lowered gonadotropin levels. Uterine edema and abnormal E2 and P4 levels during gestation are important causes of pregnancy failure in quinestrol-treated Mongolian gerbils. Quinestrol causes prolonged inhibition of fertility in Mongolian gerbils.
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Anticoncepcionais Orais Hormonais , Estrogênios/farmacologia , Quinestrol/farmacologia , Animais , Relação Dose-Resposta a Droga , Estradiol/sangue , Estro/efeitos dos fármacos , Feminino , Fertilidade/efeitos dos fármacos , Hormônio Foliculoestimulante/sangue , Gerbillinae , Hormônio Luteinizante/sangue , Folículo Ovariano/efeitos dos fármacos , Ovário/efeitos dos fármacos , Gravidez , Progesterona/sangue , Útero/efeitos dos fármacos , Útero/patologiaRESUMO
The effects of levonorgestrel (LNG) on serum levels of reproductive hormones and their receptor mRNA expression in the ovary and uterus of Mongolian gerbils were examined. The results show that serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) increased, whereas serum estradiol (E2) and progesterone (P4) decreased profoundly after LNG treatment. LNG down-regulated the mRNA expression of follicle-stimulating hormone receptor (FSHR), luteinizing hormone receptor (LHR), estrogen receptor (ER) ß and progesterone receptor (PR) in the ovary, and ERα and PR in the uterus of Mongolian gerbils. The down-regulated effects were time-dependent and dose-dependent. LNG had no obvious effects on ERα mRNA expression in the ovary. The findings suggest that LNG impairs reproductive hormone receptor expression at the molecular level in Mongolian gerbils. Also, the two ER subtypes may play different roles in the ovary, and ERß may not be the predominant ER subtype in the uterus of Mongolian gerbils. The ovary and uterus may be the important sites of action of LNG through its direct progesterone-like effects in Mongolian gerbils.
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Anticoncepcionais Femininos/farmacologia , Gerbillinae/fisiologia , Hormônios Gonadais/sangue , Levanogestrel/farmacologia , Ovário/efeitos dos fármacos , Útero/efeitos dos fármacos , Animais , Relação Dose-Resposta a Droga , Regulação para Baixo , Feminino , Gonadotropinas/sangue , Ovário/fisiologia , Reação em Cadeia da Polimerase , RNA Mensageiro/metabolismo , Receptores da Gonadotropina/metabolismo , Receptores de Esteroides/metabolismo , Fatores de Tempo , Útero/fisiologiaRESUMO
Serum estradiol (E2) and progesterone (P4) levels were measured by chemiluminescence immunoassay (CLIA) during consecutive reproductive states in Mongolian gerbils. The results show that E2 and P4 levels throughout the estrous cycle in Mongolian gerbils peaked at proestrus and estrus, respectively. During gestation in primiparous and multiparous gerbils, E2 levels reached a small peak on day 6 and a maximum peak on day 21, followed by a slight decline until parturition. Thereafter, they dropped sharply during the first 3 days of lactation and remained stable until lactation ended. P4 levels reached a peak on day 12 during gestation in primiparous gerbils, while they peaked on day 6 in multiparous gerbils. The levels of P4 then decreased until parturition. During lactation, P4 levels peaked on day 9 in primiparous gerbils, while they peaked on day 6 in multiparous gerbils, and then the levels declined gradually until lactation ended. The findings suggest that the variations of E2 levels during the estrous cycle, gestation and lactation in Mongolian gerbils are similar to those observed in rats and mice. Changes in E2 levels during different reproductive states were the same in the primiparous and multiparous gerbils, but the variations in P4 levels did not display this tendency. Changing patterns of E2 and P4 levels are suitable for the reproductive stages of Mongolian gerbils.
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Estradiol/sangue , Ciclo Estral/sangue , Gerbillinae/fisiologia , Lactação/sangue , Prenhez/sangue , Progesterona/sangue , Animais , Feminino , Masculino , Camundongos , Gravidez , Ratos , Especificidade da EspécieRESUMO
OBJECTIVE: To investigate the effect of lemon peel extracts (LPE) on the activity of lactate dehydrogenase and sucrase of Streptococcus mutans (Sm). METHODS: After serial dilution with trypticase soy broth (TSB) medium containing 2% glucose, LPE was used as the experimental group, and TSB without LPE as the control group. Sm was added to each group, which was then cultured for 6, 18, 24 and 48 hours in the anaerobic tank. The activity of lactate dehydrogenase(LDH) was measured with the method of oxidation of reduction coenzymeIand the pH value of the culture solution was also detected. The activity of the sucrose was determined with the method of coloration of 3,5-dinitrosalicylic acid. RESULTS: The activity of LDH, sucrase and the changes of solution pH were decreased with the increase of the concentration of LPE (P < 0.01). The activity of LDH were declined from (0.8025 ± 0.0913) × 10(3) U/L to (0.2099 ± 0.0283) × 10(3) U/L; the activity of sucrase were declined from (-0.0107 ± 0.0003) × 10(3) U/L to (-0.0078 ± 0.0002) × 10(3) U/L; the ΔpH were declined from (2.8067 ± 0.0404) to (2.5033 ± 0.0416) (24 h results). The differences were significant between experimental groups and the control group (P < 0.01), and there were also significant differences among experimental groups with different LPE concentration (P < 0.01). The inhibitory effect of acid generation and lactate dehydrogenas' activity of Sm were positively correlated (P < 0.01). CONCLUSIONS: LPE can inhibit the activity of lactate dehydrogenase, sucrase and the acid production capacity of the Sm in a dose dependent manner. The inhibitory effects in logarithmic phase is stronger than that in other phases of growth cycle.