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1.
Pathol Res Pract ; 260: 155440, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38964119

RESUMO

A cancer mass is composed of a heterogeneous group of cells, a small part of which constitutes the cancer stem cells since they are less differentiated and have a high capacity to develop cancer. Versican is an extracellular matrix protein located in many human tissues. The mRNA of versican has been shown to have "splicing patterns" as detected by RT-PCR, northern blot analysis, and cDNA sequencing. Based on this knowledge this study aims to reveal the splice variants of versican molecules, which are thought to be involved in the pathogenesis of the DU-145 human prostatic carcinoma cell line and prostatic cancer stem cells isolated from this cell line. In this study, RWPE-1 normal prostatic and DU-145 human prostate cancer cell lines have been used. Prostatic cancer stem cells and the remaining group of non-prostatic-cancer stem cells (bulk population) were isolated according to their CD133+/CD44+. RNA was isolated in all groups, and sequence analysis was accomplished for splicing variants by Illumina NextSeq 500 sequencing system. The results were analyzed by bioinformatic evaluation. As five isoforms of the versican gene in the differential transcript expression are analyzed, it was observed that a significant change was only found in the isoforms Versican 0 and Versican 1. In this study, we explored the function of this molecule which we think to be effective in cancer progression, and suggested that more valuable results can be obtained after the accomplishment of in vivo experiments.

2.
J Cancer ; 15(3): 590-602, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38213726

RESUMO

Increased LDH-A activity promotes tumor growth, migration, invasion, and metastasis. This study aimed to investigate the effects of the combination of LDH-A inhibitor and Docetaxel on apoptosis and epithelial-mesenchymal transition (EMT) in the murine prostate cancer (PCa) model. The prostate cancer murine model was developed subcutaneously in 50 male B57CL/6 mice using the Tramp-C2 prostate cancer cell line. From the tumor tissue samples, apoptosis analysis was performed using TUNEL staining, and EMT was investigated using western blot and qPCR. Hematoxylin-eosin staining (HE) and Periodic acid-Schiff staining were used to histopathologically examine liver and kidney tissues. Lactate levels revealed that the Warburg effect was reversed with the LDH-A inhibitor. Both serum and tumor tissue apoptosis increased, and tumor sizes reduced in PCa+LDH-A inhibitor + Docetaxel treatment groups (p<0.05). The combination of LDH-A inhibitor and Docetaxel inhibited EMT mechanism by causing a decrease in Snail, Slug, Twist, and HIF-1α expressions as well as a decrease in N-cadherin and an increase in E-cadherin levels. Reprogramming glucose metabolism with an LDH-A inhibitor can increase the effectiveness of Docetaxel on apoptosis and metastasis mechanisms in PCa.

3.
Medeni Med J ; 38(1): 8-15, 2023 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-36974384

RESUMO

Objective: In this study, the antioxidant properties of Arum maculatum plant were evaluated. This study reported for the first time the wound healing activity of the methanol extract of A. maculatum fruits. This study aimed to assess and determine the possible pharmacological activities of A. maculatum and evaluate its potential to act as a wound care plant. Methods: The antioxidant and antimicrobial activities of A. maculatum were investigated using excisional in vivo and in vitro wound healing mouse models. A total of 32 Balb-c mice were used, which were equally, divided into four groups: saline control group, control group, A. maculatum group, and Centella asiatica extract group. Treatment applications were performed topically once per day. Wound area narrowing, wound healing percentage, and epithelialization time were analyzed. Results: A. maculatum application supported the healing process in in vivo and in vitro wound models. A. maculatum contributed to the healing process by promoting granulation tissue formation, epidermal regeneration, and angiogenesis. Conclusions: Wound healing is a complex and well-organized process that requires communication between cells. The antioxidant and antimicrobial activities of A. maculatum extract have been determined by current studies. A. maculatum extract may provide significant benefits in promoting the wound healing process.

4.
J Obstet Gynaecol ; 42(3): 467-471, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34165007

RESUMO

The purpose of this study was to investigate the impact of endometrioma on oocyte morphology and fertility outcome in intracytoplasmic sperm injection (ICSI)cycles. The study material was obtained from 114 ICSI cycles of infertile women aged between 20 and 38 years with ovarian endometriomas and unexplained infertility. In total, 644 mature oocytes were included in the analysis. The rates of specific oocyte morphological abnormalities were similar between the two groups however the central granulation rate was significantly higher in the group with endometrioma (p < .05). Fertilisation rate were not significantly different between the groups (p ≥ .05) however the numbers of metaphase 2 (MII) oocytes and embryos were lower in the endometrioma group (p ≤ .05). Endometrioma was associated with a higher rate of oocytes with granular cytoplasm, despite the fertilisation rate the numbers of the MII oocytes and embryo were affected.IMPACT STATEMENTWhat is already known on this subject? The association between endometrioma and infertility is a well-known condition, but the possible mechanisms of the effects of endometrioma on women's fertility is still debated and controversial. There is limited data on the effect of endometrioma on oocyte morphology. Low oocyte quality and lower fertilisation rates might be the main cause of adverse pregnancy outcomes during in vitro fertilisation/intracytoplasmic sperm injection cycles.What do the results of this study add? Endometrioma was associated with a higher rate of oocytes with granular cytoplasm, and lower metaphase 2 oocytes and embryos.What are the implications of these findings for clinical practice and/or further research? Future studies using further oocyte quality assessment methods and prospective observational studies including live-birth rate should be designed to better understand how endometrioma affects fertility outcomes.


Assuntos
Endometriose , Infertilidade Feminina , Citoplasma , Endometriose/complicações , Feminino , Fertilização in vitro/métodos , Humanos , Infertilidade Feminina/complicações , Infertilidade Feminina/terapia , Oócitos , Gravidez , Taxa de Gravidez , Estudos Retrospectivos , Injeções de Esperma Intracitoplásmicas/métodos
5.
Parkinsons Dis ; 2021: 5553480, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34512945

RESUMO

Parkinson's disease (PD) is the second most common neurodegenerative disorder, and the main cause of PD is still not known. Until now, no cure for Parkinson's disease is yet in sight. Caffeic acid phenethyl ester (CAPE) is a polyphenolic component of the propolis, which can be derived from honeybee hive propolis. We aimed to determine the effect of intrastriatal CAPE administration as a neuroprotective agent on 6-hydroxydopamine (6-OHDA)-induced PD model. Adult male Wistar rats weighing 280-320 g were used. The PD model was induced with unilateral intrastriatal 6-OHDA injection. Treatment groups received 20 µmol/5 µL/4 day and 80 µmol/5 µL/4 day CAPE 24 h after 6-OHDA injection. Eight days after 6-OHDA application, behavioral studies (adhesive tape removal test, open-field test, cylinder test, and apomorphine-induced asymmetric rotational behavior) were performed once more to compare the effects of CAPE on behavior tests. Striatal histological verifications, immunohistochemistry, and stereological quantitation were performed. Our results for the first time showed that, besides improving the motor performance, CAPE treatment also prevents 6-OHDA-induced loss of TH-positive neurons. From our results, CAPE may be a promising clinical agent in the treatment of PD.

6.
Pharm Dev Technol ; 26(4): 431-443, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33567946

RESUMO

This study aimed to present an effective formulation targeting oral ulcers that will remain in the application site for a longer period, reducing the frequency of administration. As a candidate formulation, usnic acid (UA) was loaded into the optimum nanogels. The characterization studies included physical, rheological, and bioadhesive properties as well as in vitro release and ex vivo studies. The rheological results revealed that the nanogels present pseudoplastic flow behavior. In vitro drug release showed a prolonged pattern. In further, the chosen UA nanogels showed very low percentages of penetration and permeation. F13, which showed the highest release, suitable bioadhesive properties (0.475 ± 0.033 N/cm2) and eligible particle size (250.22 ± 4.11 nm), PDI (0.089 ± 0.052), and zeta potential (20.56 ± 0.330 mV) values were chosen for in vivo experiments. The selected UA nanogels showed effective antimicrobial activity against Bacillus Cereus and great in vivo wound healing properties. The results indicated that suitable UA nanogels with desired properties could be prepared. The therapeutic potential of the nanogels for oral ulcers was assessed using an animal model and the histopathological findings suggested that the optimized formulation is a good choice for oral ulcer treatment. Nonetheless, further research is recommended to support its efficacy by applying pharmacodynamic and pharmacokinetic studies in human individuals.


Assuntos
Benzofuranos/administração & dosagem , Nanogéis , Úlceras Orais/tratamento farmacológico , Cicatrização/efeitos dos fármacos , Adesividade , Animais , Anti-Infecciosos/administração & dosagem , Anti-Infecciosos/farmacologia , Bacillus cereus/efeitos dos fármacos , Benzofuranos/farmacologia , Preparações de Ação Retardada , Modelos Animais de Doenças , Liberação Controlada de Fármacos , Masculino , Úlceras Orais/patologia , Tamanho da Partícula , Coelhos , Reologia
7.
Crit Rev Oncog ; 26(4): 37-53, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35381146

RESUMO

Physiology of the mammalian body has been adapted to diurnal cycles of around 24 h, an evolutionary situation that affects a wide spectrum of biological events including sleep-to-wake transitions, feeding/fasting, body temperature, and hormonal regulations. The patterns of the diurnal cycle occur due to rhythmic oscillations that arise from the suprachiasmatic nucleus of hypothalamus, which also can be defined as the pacemaker of the system. The clock can be defined as a molecular machinery driven by the core clock genes that encode clock proteins in a rhythmic oscillatory fashion maintained by the light/dark cycles of the environment. Although the well-established knowledge refers to the function of the circadian rhythm as maintenance of the normal physiology, growing evidence shows that disruptions in the system usually caused by genetic and/or epigenetic misregulations may have a direct effect to lead major pathological conditions, such as carcinogenesis. This review outlines the main molecular aspects of circadian physiology, and reveals the reasons for and results of the circadian disruptions at different levels. In spite of the fact that more proof is needed for a direct correlation between circadian disruptions and oncogenesis and other pathological events, data obtained from current research supports the role of circadian rhythms in malfunctioning of the normal cellular metabolism.


Assuntos
Relógios Circadianos , Animais , Relógios Circadianos/genética , Ritmo Circadiano/genética , Humanos , Mamíferos/genética , Sono , Núcleo Supraquiasmático/metabolismo
8.
J Ethnopharmacol ; 266: 113408, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32979409

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The preparations of Phlomis aerial parts are used traditionally in Anatolia for wound healing and in inflammatory disorders. METHODS: For the identification of the active fraction, the air dried aerial parts of Phlomis rigida Labill. were extracted by methanol and fractionated successively by n-hexane, dichloromethane and ethyl acetate, respectively. The phenolic constituents were characterized by the Folin-Ciocaltheu method; the antioxidant activity was performed by ABTS and DPPH radical scavenging assays. In vitro anti-inflammatory activity was evaluated by LOX enzyme inhibition, spectrophotometrically as well as cell cultures. The wound healing properties of P. rigida extract gels were studied via in vitro cell culture methods and in vivo by excisional wound model using Balb-c mice. The P. rigida extract was analyzed and characterized by GC-FID, GC-MS, and LC-MS. RESULTS: The P. rigida methanol extract showed moderate LOX inhibitory at IC50 = 19.5 ± 2.8 µg/mL whereas the antioxidant activity was by DPPH• IC50 = 0.89 mg/mL, and by ABTS• IC50 = 0.99 mg/mL, respectively. In addition, a remarkable P. rigida extracts anti-inflammatory activity was observed in the cell culture assay, which was then confirmed by the in vitro wound healing activity applied at 0.125-0.5 mg/mL concentrations, resulting in a dose-dependent increase in wound closure at the final stage. The P. rigida gel formulation was prepared to evaluate the extract in vivo, whereas the experimental results of the new gel formulation supported the findings of the in vitro wound healing activity. CONCLUSION: The findings of this in vitro and in vivo study suggest that the wound healing and anti-inflammatory properties provide a scientific evidence of the ethnopharmacological application of Phlomis species.


Assuntos
Analgésicos/farmacologia , Anti-Inflamatórios/farmacologia , Phlomis/química , Extratos Vegetais/farmacologia , Analgésicos/administração & dosagem , Analgésicos/isolamento & purificação , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/isolamento & purificação , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Sequestradores de Radicais Livres/administração & dosagem , Sequestradores de Radicais Livres/isolamento & purificação , Sequestradores de Radicais Livres/farmacologia , Inflamação/tratamento farmacológico , Inflamação/patologia , Concentração Inibidora 50 , Camundongos , Camundongos Endogâmicos BALB C , Extratos Vegetais/administração & dosagem , Células RAW 264.7 , Cicatrização/efeitos dos fármacos
9.
J Oncol ; 2020: 1360431, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32670370

RESUMO

Expression of N-glycolyl GM3 (NeuGcGM3) ganglioside was detected in the tumor specimens of patients who were on Racotumomab anti-idiotype vaccine maintenance treatment, and prognostic significance as a biomarker was investigated. No statistically significant association was observed in the multivariate analysis between overall survival and tissue NeuGcGM3 IHC levels. Although numerically there was a difference favoring less intense IHC for better prognosis, this did not reach statistical power. However, there was a strong correlation between Racotumomab doses and overall survival (OS). Mean OS of the patient with more than 10 Racotumomab application was significantly longer than the patient who had less than 10 injections (70.7 months vs. 31.1 months, p < 0.001). We propose that, regardless of staining intensity, the presence of NeuGcGM3 in patient tissues might be an indicator of benefit in Racotumomab treatment.

10.
Molecules ; 25(11)2020 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-32531998

RESUMO

The air-dried aerial parts of Phlomis russeliana (Sims) Lag. Ex Benth. was extracted by methanol and fractionated by n-hexane, dichloromethane, and ethyl acetate, respectively. The wound healing properties of P. russeliana extract gel was evaluated using the in vivo excisional wound model using Balb-c mice. Initially, the P. russeliana methanol extract showed LOX inhibitory activity at IC50 = 23.2 µg/mL, whereas the DPPH• assay showed IC50 = 0.89 mg/mL, and the ABTS• assay showed IC50 = 0.99 mg/mL, respectively. In addition, a remarkable anti-inflammatory activity was observed in the cell culture assay. Thereafter, activity-guided fractionation was performed by LOX enzyme inhibition assays, and the structures of the two most active fractions were revealed by both GC-FID and GC/MS analyses, simultaneously. Phytol and 1-heptadecanoic acid were characterized as the active constituents. Moreover, the P. russeliana extract gel formulation was applied for in vivo tests, where the new gel formulation supported the in vitro anti-inflammatory activity findings. As a conclusion, this experimental results support the wound healing evidence based on the ethnobotanical application of Phlomis species with further potential.


Assuntos
Anti-Inflamatórios/farmacologia , Inflamação/tratamento farmacológico , Phlomis/química , Fitoterapia , Extratos Vegetais/farmacologia , Dermatopatias/tratamento farmacológico , Cicatrização/efeitos dos fármacos , Animais , Antibacterianos/farmacologia , Antioxidantes/farmacologia , Bactérias/efeitos dos fármacos , Composição de Medicamentos , Géis , Inflamação/etiologia , Inflamação/patologia , Camundongos , Camundongos Endogâmicos BALB C , Dermatopatias/etiologia , Dermatopatias/patologia
11.
Biol Pharm Bull ; 43(5): 831-838, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32378560

RESUMO

This study aims to determine the potential renal protective effects of Opuntia ficus-indica (L.) Miller (OFI) fruits against cisplatin-induced nephrotoxicity in mice. The antioxidant activity of OFI methanol extract was calculated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis-3-ethylbenzthiazoline-6-sulfonic acid (ABTS) free radical scavenging assays. Furthermore, the LC-mass spectroscopy (MS) analysis of the OFI fruit extract was carried out. Mice were treated with OFI extract (250 mg/kg) for 10 d and injected with a single dose of cisplatin (20 mg/kg) on the 7th day. The blood samples were collected to measure blood urea nitrogen (BUN) and serum creatinine level on the 10th day. Their kidneys were removed for histopathological examination. The renal morphological alterations were assessed through the mesangial matrix index and transmission electron microscopy (TEM). The OFI fruit extract showed significant in vitro antioxidant activity. In further, it was revealed that the cisplatin-induced nephrotoxicity in mice was ameliorated; this outcome was supported by both histological examination results and the depicted reduced levels of BUN and serum creatinine. The potent antioxidant compounds which were detected in the extract of OFI fruits such as myricetin, quercetin, luteolin might be responsible for the observed renoprotective effect. The results clarified that the OFI fruit extract could ameliorate cisplatin-induced renal toxicity in mice via including antioxidant and renoprotective compounds.


Assuntos
Antineoplásicos/toxicidade , Antioxidantes/uso terapêutico , Cisplatino/toxicidade , Nefropatias/tratamento farmacológico , Opuntia , Extratos Vegetais/uso terapêutico , Animais , Antioxidantes/química , Benzotiazóis/química , Compostos de Bifenilo/química , Flavonoides/análise , Flavonoides/uso terapêutico , Frutas , Rim/efeitos dos fármacos , Rim/patologia , Nefropatias/induzido quimicamente , Nefropatias/patologia , Camundongos Endogâmicos BALB C , Fenóis/análise , Fenóis/uso terapêutico , Picratos/química , Extratos Vegetais/química , Ácidos Sulfônicos/química
12.
Saudi Pharm J ; 28(3): 338-348, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32194336

RESUMO

The objective of the present research was to examine the possible usage of microemulsion based gel for fusidic acid (FA) dermal application as burn wound treatment. During the preparation of microemulsion, ethyl oleate as oil phase, tween 80 as a surfactant, ethanol as co-surfactant, water as aqueous phase were used. The prepared microemulsions were evaluated for clarity, pH, viscosity and FA content. Moreover, stability, sterility, antibacterial activity, in vitro release of the formulations were also evaluated. The results showed that the FA loaded microemulsion and microemulsion based gel formation and characteristics were related to many parameters of the components. The performed optimized microemulsion-based gel showed good stability over a period of 3 months. The antibacterial activity of microemulsion-based gel was found to be comparable with marketed cream. RAW 264.7 macrophages were used to determine cell viability (MTT assay) and nitric oxide production. MBG and FA-MBG significantly inhibit the production of the inflammatory mediator NO in LPS-stimulated RAW 264.7 cells in a concentration-dependent manner. The wound healing property was evaluated by histopathological examination and by measuring the wound contraction. The % of wound area in rats treated with FA (2%) loaded microemulsion based gel ranged from 69.30% to 41.39% in the period from 3 to 10 days. In conclusion, FA loaded microemulsion based gel could be offered as encouraging strategy as dermal systems for the burn wound treatment.

13.
Medeni Med J ; 35(4): 315-323, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33717624

RESUMO

OBJECTIVE: In this study, we examined the effects of Polypodium vulgare L. (Polypodiaceae) as a candidate to be used for wound healing scarred area. We investigated the antibacterial, and antioxidant activity of P. Vulgare on both in vivo, and in vitro wound healing using an excisional wound model in mice. METHOD: We used 32 Balb-c mice equally divided into four groups: Group 1 control, Group 2 vehicle, Group 3 Polypodium vulgare, and Group 4 Centella asiatica extract (CAE). All treatments were applied topically once in a day. The scar area, percentage wound closure and epithelization time were measured. PDGF, VEGF, and collagen immunohistochemical staining were used for evaluation. RESULTS: CAE and P. vulgare extract groups were observed to be more effective than the control and vehicle groups in terms of new vascular, epidermal and granulation tissue organization. PDGF, VEGF, and collagen immunohistochemical staining was stronger in the P.vulgare extract and CAE groups compared to the control and vehicle groups. In the P. vulgare and CAE groups, PDGF staining intensity was stronger than the control and vehicle groups, but VEGF and collagen staining in P. vulgare group was not different from the control group. CONCLUSION: P. vulgare had an effect on the injured area by regenerating the epidermis and increasing vascularization. P. vulgare extract with known antioxidant, and antimicrobial activities may be helpful as a supportive treatment in wound healing.

14.
Crit Rev Oncog ; 24(1): 27-34, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31679217

RESUMO

Tumors are composed of a variety of cancer cells, all of which contribute to tumor heterogeneity. Among these populations of cells, cancer stem cells (CSCs) have an important role in the initiation and progression of cancer. CSCs are maintained extrinsically within the tumor microenvironment, which contains both cellular and physical factors. As a barrier to metastases, cells normally undergo apoptosis (cell death process) after they lose contact with their extracellular matrix or neighboring cells. This cell death process has been termed "anoikis". The tumor cells that acquire malignant potential develop mechanisms to resist anoikis. The tumor microenvironment has been acknowledged to contribute to anoikis resistance of bystander cancer cells via modulation of the matrix stiffness, enhancement of oxidative stress, production of pro-survival soluble factors, trigger of epithelial-mesenchymal transition (EMT), and self-renewal ability, thus leading to metabolic deregulations of cancer cells. In this article, we review the significance of perivascular cells, extracellular matrix, tumor stiffness, and hypoxia in the regulation of CSC plasticity and anoikis resistance. With a better understanding of the CSC interaction with its niche and anoikis resistance, it is possible to identify potential therapeutic targets for the development of more effective treatments against cancer.


Assuntos
Anoikis , Neoplasias/etiologia , Neoplasias/metabolismo , Células-Tronco Neoplásicas/metabolismo , Microambiente Tumoral , Animais , Biomarcadores , Transformação Celular Neoplásica , Metabolismo Energético , Matriz Extracelular/metabolismo , Humanos , Hipóxia , Neoplasias/patologia , Células-Tronco Neoplásicas/patologia , Neovascularização Patológica/genética , Neovascularização Patológica/metabolismo , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia
15.
Saudi Pharm J ; 27(5): 738-752, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31297030

RESUMO

In this study, novel adhesive films were prepared for Mupirocin dermal delivery. Natural polymers as chitosan, sodium alginate and carbopol were used for films development to evaluate possible interactions and drug release properties. Solvent evaporation method was used for films preparation. Preliminary studies involved FT-IR spectroscopy and Scanning Electron Microscopy to specify interactions and morphology. Thickness, tensile strength and water uptake in phosphate buffer saline were evaluated whereas in vitro release studies were also performed. In vitro drug release studies demonstrated that mupirocin release was improved. Ex vivo bioadhesion and permeation studies using Balb-c mice were performed to check the suitability of the films. Antimicrobial ability was evaluated by agar well diffusion tests. Finally, excisional wound model applied to test the wound healing effect and evaluated macroscopic and histopathologically. One formulation was found more effective compared to the market product for wound healing at Balb-c mice.

16.
Turk J Biol ; 43(3): 179-188, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31320816

RESUMO

The clinical use of cisplatin, which is a first-line anticancer agent, is highly restricted due to its adverse effects on kidneys that lead to nephrotoxicity. Therefore, some potential reno-protective substances have been used in combination with cisplatin to cope with nephrotoxicity. Due to its high antitumor activity and oxygen-carrying capacity, we investigated the molecular effects of squalene against cisplatin-induced oxidative stress and kidney damage in mice. Single dose of cisplatin (7 mg/kg) was given to male Balb/c mice. Squalene (100 mg/kg/day) was administered orogastrically to mice for 10 days. Following sacrification, molecular alterations were investigated as analysis of the levels of oxidative stress index (OSI), inflammatory cytokines and cell survival-related proteins in addition to histopathological examinations in mice kidney tissue. The level OSI and Interferon-gamma (IFN-γ) decreased in the cisplatin and squalene cotreated mice compared to cisplatin-treated mice. Squalene treatment also increased the activation of protein kinase B (AKT). Furthermore, cisplatin-induced inactivation of mammalian target of rapamycin (mTOR) and histopathological damages were reversed by squalene. It may be suggested that squalene ameliorated the cisplatin-induced histopathological damages in the kidney through activation of AKT/mTOR signaling pathway by regulating the balance of the redox system due to its antioxidative effect.

17.
Medeni Med J ; 34(3): 297-304, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-32821452

RESUMO

OBJECTIVE: Blackthorn (Prunus spinosa L. (Rosaceae) is a shrup whose fruits are consumed as food in Turkey. This study was aimed to evaluate antioxidant activity of methanol extract of P. spinosa and its cytotoxic effects on cancer cell lines. METHOD: Methanol extract of P. spinosa fruit was evaluated for its in vitro cytotoxic activity on multiform (GBM) brain cancer (LN229, U87 and T98G) and pancreas cancer (PANC-1 and AsPC-1) cell lines. Cell viability assays were performed by calculating the percentage of viable cells using a luminescence system, and spectrophotometrically. measuring its antioxidant ABTS and DPPH radical scavenging activities. Differences were considered as statistically significant at p*<0.001 and p**<0.0005 according to unpaired student t-test. RESULTS: Methanol extract of P. spinosa fruit showed 2548±18 mg GAE/100 g correspon-ding to the total phenolic content, and moderate antioxidant activity (0.1896±0.1143 and 0.0729±0.0348) by ABTS� and DPPH� assays. CONCLUSION: To the best of our knowledge, after evaluating the results of brain and pancreas cancer cell lines, significant cytotoxic activities with 50-63% cell viability of GBM brain cancer cells were determined while no cytotoxicity was observed on pancreas cancer cell lines, PANC-1; and AsPC-1. The results of this study showed that the methanol extract of P. spinosa fruit has significant antioxidant capacity and leads to statistically significant decreased viability on glioblastoma brain cancer cells.

18.
Acta Histochem ; 121(1): 43-49, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30482507

RESUMO

Purpose Radiotherapy, chemotherapy, various tumors and invasive surgery can result in ejaculatory dysfunction and testicular insufficiency. Sperm cryopreservation is the only method which can provide a baby for couples. Cryopreservation freezes tissues and cells, allowing them to be stored for future use by stopping all biological activities. Cryopreservation can cause some harmful changes in the structure and function of the sperm. Leptin molecule plays many roles in most biological processes including the satiety and cell renewal, proliferation, angiogenesis, modulation of energy expenditure and regulation of the neuroendocrine system. Leptin was also reported to be associated with spermatogenesis in several studies. Methods This study aims to use leptin molecule as a parameter for sperm motility and DNA fragmentation before and after the cryopreservation. In this study, semen samples were taken from 30 normospermic male volunteers. Each semen sample was examined for the same parameters before and after the cryopreservation. Samples were analyzed before and after cryopreservation in terms of sperm motility by morphological sperm analysis with spermac stain dye, DNA fragmentation by TUNEL assay, ultrastructural analysis with transmission electron microscopy (TEM), seminal leptin levels by ELISA method and reactive oxygen species (ROS) levels by colorimetric method. Results Decreased sperm motility, distribution of sperm morphology and increased DNA fragmentation were determined after cryopreservation. Similarly, seminal ROS and leptin levels were also increased significantly. There was a negative correlation between seminal leptin and sperm motility. Additionally, there was a positive correlation between seminal leptin and DNA fragmentation. Conclusion According to these results, leptin molecule can be used as a marker for sperm motility and DNA fragmentation before and after cryopreservation. We think that the results of this study can contribute to further studies in the clinical aspect.


Assuntos
Criopreservação , Leptina , Preservação do Sêmen , Espermatozoides/efeitos dos fármacos , Apoptose , Fragmentação do DNA , Ensaio de Imunoadsorção Enzimática , Humanos , Leptina/farmacologia , Masculino , Espécies Reativas de Oxigênio
19.
Braz. J. Pharm. Sci. (Online) ; 55: e18295, 2019. tab, graf, ilus
Artigo em Inglês | LILACS | ID: biblio-1011644

RESUMO

Inorganic and carbon based nanomaterials are widely used against several diseases, such as cancer, autoimmune diseases as well as fungi and bacteria colonization. In this work, Santa Barbara Amorphous mesoporous silica (SBA), Halloysite Nanotubes (HNTs) and Multiwalled Carbon Nanotubes (CNTs) were loaded with fluoroquinolone Levofloxacin (LVF) to be applied as antimicrobial agents. The prepared via adsorption nanocarriers were characterized by Fourier-Transformed Spectroscopy, Scanning Electron Microscopy as well as High Pressure liquid Chromatography. In vitro release studies were carried out using Simulated Body Fluid at 37oC and data analyzed by various kinetic models showing slow dissolution over 12-24 hours. Antimicrobial studies showed improved antibacterial activity against Escherichia coli, Enterococcus faecalis, Listeria monocytogenes, Staphylococcus aureus, and Staphylococcus epidermidis compared to neat nanomaterials. CNTs were found to be the most promising candidates for LVF delivery and they were chosen to be further studied for their acute oral toxicity and histopathological examination using C57/Black mice. Histological examination depicted that drug loading did not affect mice organs morphology as well as hepatocyte degeneration, central vein degeneration and parenchymal necrosis scores. To conclude, the prepared nanomaterials present significant characteristics and can act as antimicrobial drug carriers; CNTs found to be safe candidates when orally fed to mice.


Assuntos
Nanotubos/efeitos adversos , Nanoestruturas/análise , Projetos , Toxicidade , Levofloxacino/agonistas , Técnicas In Vitro/classificação , Anti-Infecciosos
20.
J Pharm Pharmacol ; 70(10): 1401-1413, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29984824

RESUMO

OBJECTIVES: The objective of this study was to investigate the wound healing activity of Capparis ovata var. palaestina fruit extract in mice. For this aim, wound healing, in vitro antimicrobial and antioxidant activities, HPLC, phenolic and flavonoid compounds analyses were performed. METHODS: The wound healing effect was tested by excisional wound model. Wound closure was measured for 14 days and at 14th day wound healing was assessed by levels of TGF-ß, VEGF, COL1A1 and angiogenesis, granulation tissue thickness, epidermal and dermal regeneration. The antioxidant activity was calculated by DPPH and ABTS free radical scavenging assays. Antimicrobial ability was evaluated by minimum inhibitory concentration and agar well diffusion tests. KEY FINDINGS: The extract indicated significant antioxidant activity while it also exhibited antimicrobial activity. Rutin was found in the extract according to HPLC study. Moreover, the extract was found to have rich phenolic and flavonoid contents. Histological evaluation showed that extract group induced significant (P < 0.001) wound healing activity compared to control group. Furthermore, extract group increased wound healing rates by promoting granulation tissue, epidermal regeneration, angiogenesis, collagen, TGF-ß and VEGF. CONCLUSIONS: The results clarified that the extract possesses antioxidant, antimicrobial activity and thus could provide a valuable contribution to the wound healing.


Assuntos
Capparis/química , Extratos Vegetais/farmacologia , Cicatrização/efeitos dos fármacos , Indutores da Angiogênese/farmacologia , Animais , Anti-Infecciosos/farmacologia , Antioxidantes/farmacologia , Colágeno Tipo I/metabolismo , Cadeia alfa 1 do Colágeno Tipo I , Frutas/química , Masculino , Camundongos , Testes de Sensibilidade Microbiana , Extratos Vegetais/química , Pele/efeitos dos fármacos , Pele/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
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