RESUMO
The present study aimed to explore the involved lncRNA-miRNA-mRNA network in the cell cycle and proliferation after conventional treatments in Luminal A breast cancer patients.The candidate miRNAs (miRs), lncRNAs, and mRNAs were first taken from the Gene Expression Omnibus and TCGA databases. The lncRNA-miR-mRNA network was then constructed using the high-throughput sequencing data. The expression levels of selected targets were measured in the breast cancer and healthy samples by the Real-Time PCR technique and compared with the clinical outcomes by the Kaplan-Meier method.Our analysis revealed a group of differentially expressed 3 lncRNAs, 9 miRs, and 14 mRNAs in breast cancer patients. A significant expression decrease of the selected tumor suppressor lncRNAs, miRs, and genes and a substantial expression increase of the selected onco-lncRNAs, oncomiRs, and oncogenes were obtained in the patients compared to the healthy group. The plasma levels of the lncRNAs, miRs, and mRNAs were more significant after the operation, chemotherapy, and radiotherapy than the pre-treatment. The Kaplan-Meier analysis indicated that the patients with a high expression of miR-21, miR-20b, IGF1R, and E2F2 and a low expression of miR-125a, PDCD4, and PTEN had exhibited a shorter overall survival rate.Our results suggested that the underlying mechanisms of the lncRNA, miRs, and mRNAs and relevant signaling pathways may be considered predictive and therapeutic targets for breast cancer.
Assuntos
Neoplasias da Mama , MicroRNAs , RNA Longo não Codificante , Proteínas Reguladoras de Apoptose/genética , Neoplasias da Mama/genética , Ciclo Celular/genética , Proliferação de Células/genética , Feminino , Redes Reguladoras de Genes , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas de Ligação a RNA/genéticaRESUMO
Althaea officinalis (AO) is reported to have the ability to activate fibroblasts as well as anti-inflammatory and antioxidative properties. Herein, we investigated the effects of this herbal medicine on wound healing in rat models by using stereological methods. In this experiment, 48 male Wistar rats were divided into four groups randomly (n = 12): the control group with no treatment, the gel-base treated group, 5% and 10% AO-gel treated groups. The treatments were administered every 24 hours. Wound closure rate, volume densities of collagen bundles, hair follicles, and vessels, vessel's length density and mean diameter, and fibroblast populations were estimated. Fibroblast populations, hair follicles, and mean diameter of vessels in the dermis of AO-treated groups were noticeably higher than those of control and base groups. Also, collagen bundles synthesis was significantly higher in the AO10%-treated group compared to the control and base groups. According to our research and previous studies, AO has the potential to be considered as an alternative medicine in wound healing treatment; however, further clinical investigations are suggested.
Assuntos
Althaea/efeitos adversos , Vasos Sanguíneos/efeitos dos fármacos , Colágeno/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Folículo Piloso/efeitos dos fármacos , Medicina Herbária/métodos , Cicatrização/efeitos dos fármacos , Althaea/química , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Estudos de Casos e Controles , Modelos Animais de Doenças , Masculino , Ratos , Ratos WistarRESUMO
BACKGROUND: Wound healing is a complex process leading to regeneration of damaged skin tissue. Arnebia euchroma (AE) have many effective activities such as anti-inflammatory, antimicrobial, antioxidative, and anti-tumoral effects. The extract of AE has positive effects on burn wounds. This study is designed to investigate the healing effects of AE on excisional wounds in rats. MATERIALS AND METHODS: Thirty six rats with the age of 8 weeks divided into three groups. One group (E1) was treated with AE gel at a concentration of 10%. Control group (C1) received normal saline and the vehicle group (C2) was treated with carboxymethyl cellulose gel as the vehicle for 14 days. Stereological analysis was done to investigate the collagen bundle and hair follicale synthesis, vascularization, fibroblast proliferation. Pathological evaluation was also conducted. RESULTS: In this study, pathological evaluation showed severe acute inflammation in C2 group, chronic and acute inflammation in C1 and also more wound contraction in E1 in comparison with other groups. There was a meaningful difference between E1 and C1 regarding fibroblast proliferation (P < 0.05). CONCLUSION: Results of this study revealed the healing effect of AE on excisional wounds and recommend its administration after further clinical investigations.
RESUMO
AIMS: Our previous studies showed that alpha-solanine can inhibit tumor growth in cell culture and animal models of breast cancer. However, solanine is insoluble in common solvents; therefore, we developed a special nanoparticle with high-capacity solubility. The present study is aimed to deliberate the therapeutic effects of dendrosomal solanine (DNS) on a metastatic breast tumor in vitro and in vivo. MAIN METHODS: After DNS preparation and dosing procedures, forty-five mice were equally divided into five groups to investigate the anti-metastatic effects of DNS on mammary tumor-bearing mice. KEY FINDINGS: Compared to solanine, DNS significantly suppressed the proliferation of 4 T1 cells in a dose- and time-dependent manner. DNS showed a remarkable safety rate of up to 10mg/kg. A significant decrease in white blood-cell count was seen at 20mg/kg DNS in comparison with control animals. Mice treated with DNS had smaller tumor volume (mm(3)) in comparison with control and solanine groups. Moreover, the incidence of the breast tumor metastases was about 67% in the control animals, where as solanine and DNS 1mg/kg were about 22% and 0%, respectively. Furthermore, the number of metastases per mouse varied from one to three. The tissues of tumor, brain, liver, spleen, and lung showed higher expression levels of Bcl-2 but lower expression levels of Bax, MMP-2, MMP-9, mTOR, and Akt in DNS-treated mice than control and solanine groups. SIGNIFICANCE: The findings suggest that DNS has a more impactful therapeutic effect than solanine on 4 T1-induced breast tumorigenesis via influencing the tissue microenvironment.
Assuntos
Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Portadores de Fármacos/administração & dosagem , Nanopartículas/administração & dosagem , Solanina/administração & dosagem , Animais , Linhagem Celular Tumoral , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Resultado do TratamentoRESUMO
BACKGROUND: Recent studies have mainly focused on the roles of serum calcium and phosphorus product in the development of valvular heart failure. We determined the association of calcium-phosphorus product with the severity of heart valve failure in patients under chronic hemodialysis (being under hemodialysis for 6 months or more) in Boo-Ali Hospital in 2012 and 2013. METHODS: It was a cross-sectional, descriptive, comparative study. Thirty-three patients undergoing chronic hemodialysis were recruited to the study. All the patients were hospitalized at Boo-Ali Hospital. The study was done in a 2 years long time frame and the association of calcium-phosphorus product and severity of heart valve failure was evaluated among them. RESULTS: The results demonstrated that there was no significant association between age, gender, renal failure cause and hemodialysis duration (P > 0.05). Our results showed a negative correlation between the severity of cardiac valves failure and CA × P level. It was not a meaningful correlation though (P > 0.05). CONCLUSIONS: Based on the obtained results, it is concluded that there is not any association between calcium-phosphorus product and the severity of heart valve failure in patients under chronic hemodialysis.
RESUMO
Delayed wound healing process is one of the most important concerns in diabetes. Healing of wounds has four phases, namely, hemostasis, inflammation, proliferation, and remodeling. For a successful repair, all four factors must occur properly. Hence, we aimed to evaluate the healing effects of Hypericum perforatum (HP) on full-thickness diabetic skin wounds by using stereological methods. Forty-eight female diabetic rats were randomly divided into four groups (n = 12): gel base treated group, HP 5% gel treated group, HP 10% gel treated group, and the control group which received no treatment. A circular 1 cm(2) full-thickness wound was created on the animal's neck and wound area was measured every three days. After sacrificing the animals, skin samples were fixed and prepared for stereological evaluations. Based on the results, HP treated group showed faster wound closure rate in comparison with control and vehicle groups (P < 0.05). In addition, numerical density of fibroblasts, volume density of collagen bundles, and mean diameter and volume densities of the vessels in HP group were significantly higher than control and vehicle groups. The results of this study showed that HP has the ability to improve tissue regeneration by enhancing fibroblast proliferation, collagen bundle synthesis, and revascularization.
RESUMO
Alpha-solanine, a naturally steroidal glycoalkaloid, is found in leaves and fruits of plants as a defensive agent against fungi, bacteria and insects. Herein, we investigated solanine toxicity in vitro and in vivo, and assessed its protective and the therapeutic effects on a typical animal model of breast cancer. The study conducted in three series of experiments to obtain (i) solanine effects on cell viability of mammary carcinoma cells, (ii) in vivo toxicity of solanine, and (iv) the protective and therapeutic effects of solanine on animal model of breast cancer. Alpha-solanine significantly suppressed proliferation of mouse mammary carcinoma cells both in vitro and in vivo (P<0.05). Under the dosing procedure, 5 mg/kg solanine has been chosen for assessing its protective and therapeutic effects in mice breast cancer. Tumor take rate in the solanine-treated group was zero compared with a 75% rate in its respective control group (P<0.05). The average tumor size and weight were significantly lower in solanine-treated animals than its respective control ones (P<0.05). Proapoptotic Bax protein expression increased in breast tumor by solanine compared with its respective control group (P<0.05). Antiapoptotic Bcl-2 protein expression found to be lower in solanine-treated animals (P<0.05). Proliferative and angiogenic parameters greatly decreased in solanine-treated mice (P<0.05). Data provide evidence that solanine exerts a significant chemoprotective and chemotherapeutic effects on an animal model of breast cancer through apoptosis induction, cell proliferation and angiogenesis inhibition. These findings reveal a new therapeutic potential for solanine in cancer.
Assuntos
Antineoplásicos/farmacologia , Neoplasias Mamárias Experimentais/tratamento farmacológico , Neoplasias Mamárias Experimentais/prevenção & controle , Solanina/farmacologia , Animais , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Humanos , Neoplasias Mamárias Experimentais/irrigação sanguínea , Neoplasias Mamárias Experimentais/patologia , Camundongos , Metástase Neoplásica , Neovascularização Patológica/tratamento farmacológico , Solanina/uso terapêuticoRESUMO
The current study examines the protective effect of oxytocin (OT) on cardiomyocyte apoptosis modulated by mitochondrial ATP-dependent potassium (mitoKATP) channel and permeability transition pore (mPTP) in the preconditioned myocardium of anesthetized rats. Eighty rats were equally divided into eight groups. The hearts of all animals except for the sham group were subjected to 25 min ischemia and 120 min reperfusion. Oxytocin, 5-hydroxydeconoate (5-HD), a specific inhibitor of the mitoKATP channel, and atractyloside (ATRC), an mPTP opener, were used prior to ischemia. Hemodynamic parameters were recorded throughout the experiment. Evaluations were made by infarct size, plasma lactate dehydrogenase level (LDH), transmission electron microscopy (TEM) and immunohistochemistry studies. OT prevented mean arterial pressure drop during early phase of ischemia and reperfusion. Treatment with OT before IR induction normalizes cardiomyocytes both in light microscopy and TEM observations. In addition, OT significantly reduced TUNEL- and increased Bcl-2-labeled positive cell number relative to IR (p<0.05). However, 5HD or ATRC inhibited the protective effects of OT on cardiomyocytes damaged by IR (p<0.05). Ultrastructural changes including extensive myofibril loss, sarcolemmal disruption and mitochondrial swelling due to amorphous dens bodies indicate necrosis induction in 5HD and ATRC as well as in IR groups. Restoration of immunohistochemistry parameters and protection against IR-induced ultrastructural changes confirm OT cardioprotective effects via mitoKATP channel and mPTP modulation in apoptosis induced by ischemia-reperfusion.