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1.
Biol Pharm Bull ; 45(5): 561-568, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35185080

RESUMO

Ovarian cancer has long been considered the second-highest cancer threat to women's reproductive system with high mortality. This is ascribed to the absence of highly efficient therapy and cancer metastasis. Accordingly, there is an urgent need for the development of new agents. Recently, Traditional Chinese medicine has gained extensive interest because of its safe use, validity, and distinct pharmacological effects. Polyphyllin E (PPE), as a major constituent in Rhizoma Paridis, is a promising cancer-fighting agent. However, the effect of PPE on ovarian cancers as well as associated latent mechanisms is still not completely understood. In this study, PPE was found to prohibit the proliferation of SK-OV-3 and OVCAR-3 ovarian cancer cells, causing marked cell death. Additionally, low-dose PPE could also inhibit motility and invasion of ovarian cancer cells. The mechanistic assessment revealed PPE-mediated matrix metalloproteinases, i.e., MMP2 and MMP9, inhibition via the AKT-nuclear factor kappa B (AKT/NF-κB) signaling pathway. Rescue experiments with transfection of AKT lentiviral particles remarkably reversed PPE inhibitory effects against ovarian cancer cells. In conclusion, PPE could inhibit proliferation of ovarian cancer cell migration and invasion by down-regulating the AKT/NF-κB pathway. Moreover, it has the potential to act as a novel agent for ovarian cancer treatment.


Assuntos
Neoplasias Ovarianas , Proteínas Proto-Oncogênicas c-akt , Apoptose , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Humanos , NF-kappa B/metabolismo , Neoplasias Ovarianas/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo
2.
J Obstet Gynaecol ; 42(6): 1759-1768, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35260025

RESUMO

The aim of this study was to identify the effect of hyperglycaemia on placentas of gestational diabetes mellitus (GDM) women with macrosomia and normal pre-pregnancy body mass index (BMI), and uncover the molecular mechanism of hyperglycaemia on trophoblast cells in vitro. GDM women with normal pre-pregnancy BMI were divided into GM group (macrosomia, n = 30) and GN group (normal birth weight, n = 35). The study showed GM group had more adverse pregnancy outcomes and higher levels of gestational weight gain, blood glucose and triglyceride. After adjustment for confounding factors, just the fasting plasma glucose level and HbA1c percentage were related to the incidence of GDM-induced macrosomia with normal pre-pregnancy BMI. Meanwhile, the fasting blood glucose was closely related to the placental weight and placental PCNA expression. Furthermore, the in vitro model for placenta showed that hyperglycaemia significantly promoted trophoblast cell proliferation and activated ERK1/2 phosphorylation. ERK1/2 inhibitor markedly suppressed hyperglycaemia-induced trophoblastic proliferation. The fasting plasma glucose and placenta are closely related with the development of GDM-induced macrosomia with normal pre-pregnancy BMI. The mechanism may be hyperglycaemia promotes trophoblast cell proliferation via ERK1/2 signalling. It provides scientific evidence for optimising outcomes of GDM women with normal pre-pregnancy BMI.IMPACT STATEMENTWhat is already known on this subject? Gestational diabetes mellitus (GDM) is one of the strongest risk factors correlated with macrosomia. The hyperglycaemic intrauterine environment affects not only the foetus but also the placental development and function in humans and experimental rodents. However, placental abnormalities associated with maternal diabetes have been inconsistently reported, possibly because of population differences in pre-pregnancy weight, diabetes types, glycemic control or pregnancy complication, and the molecular mechanism of hyperglycaemia on trophoblast cells in vitro was not clearly stated.What do the results of this study add? This is the first study to identify the effect of hyperglycaemia on placentas of gestational diabetes mellitus (GDM) women with macrosomia and normal pre-pregnancy body mass index (BMI), and uncover the molecular mechanism of hyperglycaemia on trophoblast cells in vitro.What are the implications of these findings for clinical practice and/or further research? Understanding placental changes in the environment of abnormal glucose metabolism which can establish the maternal-placental-foetal interface dysfunction as a potential source of adverse pregnancy outcomes is very necessary. Our study found the fasting plasma glucose and placenta are closely related with the development of GDM-induced macrosomia with normal pre-pregnancy BMI. The mechanism may be hyperglycaemia promotes trophoblast cell proliferation via ERK1/2 signalling. It provides scientific evidence for optimising outcomes of GDM women with normal pre-pregnancy BMI, and could be used for the following studies of relationship between placenta and childhood complications.


Assuntos
Diabetes Gestacional , Hiperglicemia , Peso ao Nascer , Glicemia/metabolismo , Índice de Massa Corporal , Proliferação de Células , Criança , Feminino , Macrossomia Fetal/epidemiologia , Glucose/metabolismo , Hemoglobinas Glicadas/metabolismo , Humanos , Hiperglicemia/complicações , Placenta/metabolismo , Gravidez , Antígeno Nuclear de Célula em Proliferação/metabolismo , Triglicerídeos , Trofoblastos , Aumento de Peso
3.
J Pharmacol Sci ; 136(2): 66-72, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29428295

RESUMO

In recent years, plant-derived extracts are increasing interest from researchers worldwide due to good efficacy and lower side effects. Among the different plant extracts, Dracorhodin perchlorate (DP) is originated from Dragon's blood which has long been used as a natural medicine with various pharmacological activities. In the present study, we have explored the potential regulation of DP on fibroblast proliferation which promotes wound healing both in vitro and in vivo. DP at treatment of 12-24 h significantly induced fibroblast proliferation which is associated with increasing level of phosphorylated-extracellular signal-regulated kinase (ERK). Moreover, if ERK is halted with siRNA, DP cannot induce fibroblast proliferation. In vivo, DP ointment treatment at low- (2.5 µg/mL), medium- (5 µg/mL) and high-(10 µg/mL) doses, rat wounds healed more rapidly compared with the control group. After DP treatment for 7 days, Serpin family H member 1 (SERPINH1) staining confirmed enhanced fibroblast proliferation in the wound tissue. Finally, phosphorylated-ERK in the wound tissue remarkably increased with DP ointment treatment. Therefore, DP may be developed into a potential lead compounds for the treatment of wounds in clinical trials in the near future.


Assuntos
Benzopiranos/farmacologia , Proliferação de Células/efeitos dos fármacos , Fibroblastos/fisiologia , Fitoterapia , Cicatrização/efeitos dos fármacos , Cicatrização/fisiologia , Ferimentos e Lesões/tratamento farmacológico , Animais , Benzopiranos/isolamento & purificação , Células Cultivadas , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Masculino , Fosforilação , Extratos Vegetais/química , Ratos Wistar , Fatores de Tempo , Ferimentos e Lesões/enzimologia , Ferimentos e Lesões/fisiopatologia
4.
Front Vet Sci ; 11: 1368579, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38764851

RESUMO

Introduction: The increasing resistance of R. anatipestifer has posed a significant threat to the poultry industry in recent years. The tet gene is the primary determinant of tetracycline resistance in numerous bacteria, and the enzyme modification gene tet(X) is predominantly detected in tetracycline-resistant R. anatipestifer strains. Methods: In this study, we evaluated the susceptibility of both the standard strain and clinical isolates of R. anatipestifer to doxycycline. And the expression levels of tet(X), tet(A), and tet(O) genes were detected. To assess drug susceptibility, shuttle plasmids were constructed to transfer the tet(X) gene into the standard strain of R. anatipestifer followed by treatment with chlorogenic acid. Results and discussion: The results revealed that the minimum inhibitory concentration of doxycycline for the standard strain was 0.25µg/mL, whereas it exceeded 8µg/mL for the clinical isolates. Furthermore, there was a significant upregulation observed in expression levels of tet(X), tet(A), and tet(O) genes among induced strains. Interestingly, when transferring the tet(X) gene into the standard strain, its sensitivity to doxycycline decreased; however, MIC values for chlorogenic acid remained consistent between both standard and drug-resistant strains of R. anatipestifer. Moreover, we made a surprising discovery that screening passage with chlorogenic acid resulted in increased sensitivity of R. anatipestifer to doxycycline. Further analysis demonstrated a reversal in expression trends among three differentially expressed genes within induced drug resistance group after intervention with chlorogenic acid. The main objective behind this study is to investigate both killing effect exerted by chlorogenic acid on drug-resistant R. anatipestifer as well as its regulatory impact on drug resistance genes. This will provide novel insights and theoretical basis towards development of chlorogenic acid as a promising drug for treatment and control of drug resistance in R. anatipestifer.

5.
Int Immunopharmacol ; 135: 112283, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38772299

RESUMO

Toll-like receptors (TLRs) play a crucial role in mediating immune responses by recognizing pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs), as well as facilitating apoptotic cell (ACs) clearance (efferocytosis), thus contributing significantly to maintaining homeostasis and promoting tissue resolution. In this study, we investigate the impact of TLR agonists on macrophage efferocytosis. Our findings demonstrate that pretreatment with the TLR agonist lipopolysaccharide (LPS) significantly enhances macrophage phagocytic ability, thereby promoting efferocytosis both in vitro and in vivo. Moreover, LPS pretreatment confers tissue protection against damage by augmenting macrophage efferocytic capacity in murine models. Further examination reveals that LPS modulates efferocytosis by upregulating the expression of Tim4.These results underscore the pivotal role of TLR agonists in regulating the efferocytosis process and suggest potential therapeutic avenues for addressing inflammatory diseases. Overall, our study highlights the intricate interplay between LPS pretreatment and efferocytosis in maintaining tissue homeostasis and resolving inflammation.


Assuntos
Lipopolissacarídeos , Macrófagos , Camundongos Endogâmicos C57BL , Fagocitose , Animais , Fagocitose/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos , Receptores Toll-Like/metabolismo , Receptores Toll-Like/agonistas , Inflamação/tratamento farmacológico , Inflamação/imunologia , Masculino , Humanos , Apoptose/efeitos dos fármacos , Células RAW 264.7 , Proteínas de Membrana/metabolismo , Eferocitose
6.
Clin Transl Oncol ; 25(10): 2901-2910, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37000289

RESUMO

BACKGROUND: Hsa_circ_0001535 is involved in biological processes in various tumors. However, the biological effects and related mechanism of hsa_circ_0001535 in ovarian cancer (OC) is unclear. This work is aimed to probe the biological function and underlying mechanism of hsa_circ_0001535 in OC, especially sponged with mi-RNA, require further elucidation. METHODS: Hsa_circ_0001535 expression in OC tissues and cell lines were examined by qRT-PCR. Hsa_circ_0001535 overexpression model was constructed by lentivirus-mediated transfection in two OC cell lines, and the biological functions of hsa_circ_0001535 were evaluated by CCK-8, transwell assay and Western blot. Dual luciferase reporter gene assay was respectively used to explore the relationship between hsa_circ_0001535 and miR-593-3p, as well as miR-593-3p and PTEN. The expression of miR-593-3p and PTEN were detected by qRT-PCR in two OC cell lines and OC tissues. RESULTS: Hsa_circ_0001535 was down-regulated in OC tissues and cell lines. Hsa_circ_0001535 overexpression inhibited proliferation, migration and EMT marker expression in OC cells. Of interest, hsa_circ_0001535 targeted miR-593-3p and reduced its RNA level in OC cells. PTEN was a target gene of miR-593-3p, which was up-regulated by inhibiting miR-593-3p in OC cells. Furthermore, miR-593-3p mimic treatment reversed the up-regulation of PTEN by hsa_circ_0001535 overexpression in OC cells. CONCLUSIONS: The above results showed that hsa_circ_0001535 acted as a molecular sponge for miR-593-3p to repress miR-593-3p expression, and promoted the expression of PTEN, thus inhibited proliferation and migration of OC cells. Our research provides a potential therapeutic target for ovarian cancer patients.


Assuntos
MicroRNAs , Neoplasias Ovarianas , Feminino , Humanos , Western Blotting , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Genes Reporter , MicroRNAs/genética , Neoplasias Ovarianas/genética , PTEN Fosfo-Hidrolase/genética , RNA Circular/genética
7.
Acta Biochim Pol ; 69(4): 745-751, 2022 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-36272152

RESUMO

MicroRNA-650 (miR-650) has been shown to regulate the development of human cancers. The present study investigated the role of miR-650 in ovarian cancer by targeting Krüppel-like factor 12 (KLF12). The results showed a down-regulation of miR-650 in tissues and cell lines. Overexpression of miR-650 caused a substaining decrease in the viability of CAOV3 cells by promoting apoptotic cell death. In silico analysis and dual luciferase assay revealed KLF12 as a potential target of miR-650. Unlike miR-650, KLF12 showed a substantial up-regulation in ovarian cancer tissues and cell lines. However, miR-650 overexpression suppressed KLF12 expression posttranscriptionally. Intrestingly, KLF12 knockdown inhibited the viability of CAOV3 cells by promoting apoptotic cell death. However, the expression of KLF12 eliminated the tumor suppressing effects of miR-650 in CAOV3 cells. Additionally, KLF12 knockdown or miR-650 overexpression suppressed CAOV3 cell migration and invasion. However, KLF12 overexpression eliminated the inhibitory effects of miR-650 on the migration and invasion of CAOV3 cells. Taken together, these results suggest that miR-650/KLF12 axis regulates the viability, migration, and invasion of CAOV3 cells an0d may prove to be an important therapeutic taregt.


Assuntos
MicroRNAs , Neoplasias Ovarianas , Humanos , Feminino , Neoplasias Ovarianas/genética , Fatores de Transcrição Kruppel-Like/genética , Fatores de Transcrição Kruppel-Like/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Movimento Celular/genética , Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica
8.
Aging (Albany NY) ; 14(11): 4699-4713, 2022 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-35687899

RESUMO

PURPOSE: This article researched circ_0063804 effects on ovarian cancer (OC) development and resistance to cisplatin, aiming to provide a new target for OC therapy. METHODS: A total of 108 OC patients participated in this study. The circle structure of circ_0063804 was investigated using RNase R. Circ_0063804 expression in OC cells were up-regulated or down-regulated by transfection. Cell proliferation was assessed by cell counting kit-8 assay and colony formation assay. Flow cytometry was used to detect apoptosis. OC cells resistance to cisplatin was explored through MTT assay. Luciferase reporter assay was performed. qRT-PCR and Western blot was applied to research genes expression. Xenograft tumor experiment was conducted using nude mice. Ki67 expression in xenograft tumor was detected by immunohistochemistry. RESULTS: Circ_0063804 expression was up-regulated in OC patients and indicated poor prognosis (P < 0.05). Circ_0063804 had a stable circle structure. Circ_0063804 enhanced proliferation, resistance to cisplatin and reduced apoptosis of OC cells (P < 0.01). miR-1276 was down-regulated in OC patients and sponged by circ_0063804. CLU was directly inhibited by miR-1276 and up-regulated in OC patients. Circ_0063804 exacerbated malignant phenotype and resistance to cisplatin of OC cells in vitro by enhancing CLU expression via sponging miR-1276 (P < 0.01). Circ_0063804 silencing inhibited OC cells growth, resistance to cisplatin and Ki67 expression in vivo (P < 0.01). CONCLUSION: Circ_0063804 promoted OC cells proliferation and resistance to cisplatin by enhancing CLU expression via sponging miR-1276.


Assuntos
MicroRNAs , Neoplasias Ovarianas , Animais , Proliferação de Células/genética , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Clusterina , Feminino , Humanos , Antígeno Ki-67 , Camundongos , Camundongos Nus , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , RNA Circular/genética
9.
Onco Targets Ther ; 14: 2711-2726, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33907415

RESUMO

OBJECTIVE: Cisplatin resistance is one of the main reasons for treatment failure in ovarian cancer (OC). Here, the effects of LINC00184 on cisplatin-resistant OC were studied. PATIENTS AND METHODS: LINC00184, miR-1305 and CNTN1 expression in tissues from 70 OC patients was determined by qRT-PCR, in situ hybridization and Western blot. OC cell lines and OC cisplatin-resistant cell lines were cultured. Cells were transfected using Lipofectamine 2000 and treated with 100 nM cisplatin. Cell proliferation and apoptosis were researched by the CCK-8 assay and flow cytometry. A dual-luciferase reporter gene assay and RNA pull-down were performed to explore the relationship between two genes. LINC00184, miR-1305 and CNTN1 expression in cells was detected by qRT-PCR and Western blot. An in vivo experiment was conducted using nude mice. Ki67 and CNTN1 expression and apoptosis of xenograft tumors were investigated using immunohistochemistry and a TUNEL assay. RESULTS: LINC00184 was up-regulated in OC clinical tissues and OC cells, especially in cisplatin-resistant OC patients and cells (p<0.01 or p<0.0001). LINC00184 overexpression significantly enhanced OC cell proliferation and cisplatin resistance, and inhibited OC cell apoptosis (p<0.05 or p<0.01). LINC00184 elevated CNTN1 expression via sponging miR-1305. LINC00184 overexpression markedly exacerbated the malignant phenotype of OC cells and cisplatin-resistant OC cells via the miR-1305/CNTN1 axis (p<0.01). Silencing of LINC00184 significantly suppressed OC cell growth and cisplatin resistance in vivo (p<0.01). LINC00184 silencing inhibited Ki67 and CNTN1 expression and promoted apoptosis of xenograft tumors. CNTN1 overexpression promoted proliferation and cisplatin resistance, and reduced apoptosis of OC cells (p<0.05 or p<0.01). CONCLUSION: LINC00184 promoted OC cell proliferation and cisplatin resistance by elevating CNTN1 expression via sponging miR-1305.

10.
Artigo em Inglês | MEDLINE | ID: mdl-29333188

RESUMO

Dracorhodin perchlorate (DP) is extracted from Dragon's blood, which is widely used in traditional Chinese medicine, especially in wound healing. The aim of this paper is to investigate the influence of DP ointment, which contained DP dissolved in DMSO and mixed with Vaseline, on cutaneous wound healing in Wistar rats. Forty Wistar rats were divided into two groups: control and DP groups. The skin on the back of each rat was punched with two full-thickness wounds and then treated with the corresponding drug. After 3, 7, 10, 14, and 21 days, four rats were sacrificed for immunological, biochemical, and histological analyses. Compared with the control treatment, DP could significantly promote wound closure. Histological and biochemical analyses of the skin biopsies also showed that DP regulated the expression of inflammatory responses by TNF-α and IL-ß and by supporting wound tissue growth and collagen deposition. Western blot revealed that DP could also facilitate the expression of EGF and VEGF proteins. In conclusion, DP promotes wound healing.

11.
Endocrine ; 54(3): 691-699, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27481362

RESUMO

A great quantity of gestational diabetes mellitus with normal prepregnancy body mass index have emerged with the new criteria of gestational diabetes mellitus in China based on the International Diabetes in Pregnancy Consensus group criteria, and understanding placental changes and how they affect outcomes are necessary in order to develop effective management approach. The aim of this study was to prospectively explore the effect of active management starting from the late second trimester in gestational diabetes mellitus women with normal prepregnancy body mass index on pregnancy outcomes and placental ultrastructures, and to provide scientific evidences for optimizing the management of gestational diabetes mellitus in China. Gestational diabetes mellitus women with normal prepregnancy body mass index in the same period of this prospective cohort study were divided into intervention group (n = 51) and control group (n = 55). The intervention group was managed rigorously, while the control group received conventional prenatal cares. The glucose profile, gestational weight gain and pregnancy outcomes were followed up and placental ultrastructures were observed and recorded by transmission electron microscopy. The blood glucose level and gestational weight gain in intervention group were significantly better controlled than those in control group (P < 0.01). The incidences of fetal distress, cesarean section and large for gestational age were significantly lower in intervention group than in control group (P < 0.05). There was a significant reduction in the incidence of abnormal placental ultrastructure in the intervention group (P < 0.01). After adjustment for confounding factors, the undesirable glycemic control and conventional management were related to abnormal placental ultrastructure (P < 0.05). Meanwhile, the undesirable glycemic control, abnormal placental ultrastructure and conventional management made sense in the incidence of fetal distress (P < 0.05), and the target glycemic control, recommend weight gain and active management were associated with reductions in the prevalence of cesarean delivery and large for gestational age (P < 0.05). The active management of gestational diabetes mellitus women with normal prepregnancy body mass index can improve pregnancy outcomes and placental ultrastructures, and the abnormal placental ultrastructure might be closely associated with the undesirable glycemic control and adverse pregnancy outcomes.


Assuntos
Diabetes Gestacional/terapia , Placenta/ultraestrutura , Resultado da Gravidez , Adulto , Índice de Massa Corporal , Feminino , Humanos , Modelos Logísticos , Gravidez , Segundo Trimestre da Gravidez , Estudos Prospectivos
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