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1.
Neurobiol Learn Mem ; 180: 107410, 2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33610772

RESUMO

Repetitive Transcranial Magnetic Stimulation (rTMS) is a non-invasive neuromodulation technique which is increasingly used for cognitive impairment in Alzheimer's Disease (AD). Although rTMS has been shown to modify Brain-Derived Neurotrophic Factor (BDNF) and oxidative stress levels in many neurological and psychiatric diseases, there is still no study evaluating the relationship between memory performance, BDNF, oxidative stress, and resting brain connectivity following rTMS in Alzheimer's patients. Furthermore, there are increasing clinical data showing that the stimulation of strategic brain regions may lead to more robust improvements in memory functions compared to conventional rTMS. In this study, we aimed to evaluate the possible disease-modifying effects of rTMS on the lateral parietal cortex in AD patients who have the highest connectivity with the hippocampus. To fill the mentioned research gaps, we have evaluated the relationships between resting-state Functional Magnetic Resonance Imaging (fMRI), cognitive scores, blood BDNF levels, and total oxidative/antioxidant status to explain the therapeutic and potential disease-modifying effects of rTMS which has been applied at 20 Hz frequencies for two weeks. Our results showed significantly increased visual recognition memory functions and clock drawing test scores which were associated with elevated peripheral BDNF levels, and decreased oxidant status after two weeks of left lateral parietal TMS stimulation. Clinically our findings suggest that the left parietal region targeted rTMS application leads to significant improvement in familiarity-based cognition associated with the network connections between the left parietal region and the hippocampus.

2.
Pharm Dev Technol ; : 1-11, 2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33583320

RESUMO

Conventional formulations can not achieve wound healing efficiently and fail to accelerate wound regeneration. To overcome these problems, it was planned to develop nanoformulations that perform a positive effect on the wound healing duration and are suitable for topical use. In this study, liposomal film formulations that encapsulated d-panthenyl triacetate (PTA) and coenzyme Q10 (CoQ10) were optimized by using response surface methodology (RSM) and were analyzed for their wound healing efficacy and cytotoxicity on fibroblast (CCD1079 Sk) and keratinocyte (HEKa) cells. Swelling index, puncture strength, and puncture deformation values, which were choosen as dependent variables for the liposomal film formulation were found as 556.9% ± 21.3, 3.98 ± 0.98 N/mm2, and 6.57% ± 1.12, respectively. Cumulative release of 65.32% for PTA and 12.23% for CoQ10 was obtained after 24 hours of in vitro release study in sink conditions. The in vitro cytotoxicity and wound healing assay results suggested that optimum formulation could be used safely on fibroblast and keratinocyte cells and provided wound closure entirely after 24 h. Consequently, the optimum liposomal film containing PTA and CoQ10 formulations could be proposed as an innovative approach in wound healing treatment, considering their release, mechanical properties, stability, and effectiveness.

3.
Dermatol Ther ; 34(1): e14733, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33389789

RESUMO

There is a growing body of evidence linking rosacea to various systemic disorders, even though data regarding the association between rosacea and cardiovascular diseases are presently controversial. We sought to investigate the potential association of rosacea with subclinical atherosclerosis and serum proinflammatory/proatherogenic markers. This study included 44 patients with rosacea and 44 age-matched and sex-matched healthy control subjects. Patients with traditional cardiovascular risk factors or a history of cardiovascular events were excluded. Demographic, clinical, and laboratory data, including serum interleukin-1 beta (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and high-sensitivity C-reactive protein (hs-CRP) levels were assessed. Carotid intima-media thickness (CIMT) and carotid plaques were measured by carotid ultrasonography. Serum IL-1ß (P < .001), IL-6 (P < .001), TNF-α (P < .001), and hs-CRP (P < .001) levels were significantly higher in the patient group compared with the control group. Mean CIMT values did not differ significantly between the patient group and control group (P > .05). Patients with moderate to severe rosacea had a significantly greater CIMT than those with mild rosacea (P = .047). Rosacea patients with eye involvement had a significantly greater CIMT than those without eye involvement (P = .008). There was no significant correlation between CIMT values and inflammation parameters. As conclusion, in the absence of other traditional cardiovascular risk factors, rosacea does not seem to affect mean CIMT value. However, specific subgroups such as patients with moderate to severe disease or with eye involvement are associated with increased subclinical atherosclerosis and may require additional attention for cardiovascular disease prevention.

4.
Clin Exp Hypertens ; : 1-6, 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33172302

RESUMO

Objective: Hypertension is a multi-factorial process prevalent in developed as well as in developing countries. Urotensin-II, different antioxidants, free radicals, and inflammatory biomarkers play an essential role in the cardiovascular system. The aim of this study is to investigate Urotensin-II, oxidative stress, and inflammation markers in normotensive, hypertensive, and resistant hypertensive patients. Methods: Fifty resistance hypertensive (rHT) patients, 50 hypertensive patients, and 50 age gender matched normotensive controls (NT-control) were enrolled. Urotensin-II (UII), total oxidant status (TOS), total antioxidant status (TAS), native thiol (NT), total thiol (TT), disulfide (DIS), interleukin 1 beta (IL1ß), interleukin 6 (IL6), tumor necrosis factor-alpha (TNFα), high sensitive c reactive protein (hsCRP), high-density lipoprotein (HDL) low-density lipoprotein (LDL), and total cholesterol (TC) were evaluated. Results: Serum levels of UII, IL1ß, IL6, TNFα, DIS, TOS, and OSI were found higher in rHT and HT as compared to NT-control (p < .001). On the contrary, serum levels of TT, TAS, and NT were lower in rHT and HT as compared to NT-control (p < .001). While TC, hsCRP, TOS, OSI, UII, IL1ß, IL6, and TNFα levels increase from HT to rHT group (p < .001); TAS and NT levels decrease from HT to rHT group (p < .001). Conclusions: UII levels, oxidative stress, and inflammation are higher in rHT and HT, while antioxidants and thiol levels are lower than the NT-control. Our study clearly showed that rHT and HT are more susceptible to impaired states of antioxidants, oxidative stress, and free radicals.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33052461

RESUMO

PURPOSE: Reactive oxygen radicals play an important role in tumor formation, progression, and invasion. In this study, the aim was to investigate the relationship between the oxidative stress values of tumor core, edge, and healthy thyroid tissue in thyroid tumors. METHODS: A total of 51 patients with thyroid tumor, 24-malignant, and 27-benign, were included in this study. Samples, measuring 5 × 5 × 5 mm, were taken from the tumor core, edge, and healthy thyroid tissue of the participants. Total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) values were examined. The oxidative stress values of core, edge, and healthy thyroid tissue of all tumors (n = 51) were compared according to the localization. The participants were divided into two groups as malignant (Group 1: Differentiated thyroid cancers) and benign (Group 2: Multinodular goiter). The groups were compared according to tissue localizations. RESULTS: The TOS value of tumor edge was significantly higher than the values of tumor core and healthy thyroid tissue. The OSI value of tumor edge was significantly higher than the values of tumor core and healthy thyroid tissue. There was no significant difference between Group 1 and Group 2 in terms of TAS, TOS, and OSI values of tumor core. The OSI values in tumor edge and healthy thyroid tissue were significantly higher in Group 1 than in Group 2. There was no significant difference between the groups in terms of TAS and TOS values of tumor edge and healthy thyroid tissue. CONCLUSION: The oxidative stress values of tumor edge were significantly higher than the tumor core and healthy thyroid tissue values. The oxidative stress values of tumor edge and healthy thyroid tissue were significantly higher in malignant thyroid tumors compared to benign thyroid tumors.

6.
Sleep Breath ; 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-33083922

RESUMO

BACKGROUND: Restless legs syndrome [RLS] is known as a disease of iron and dopaminergic dysregulation but inflammatory processes might also have a role in the pathogenesis. In this study, we compared the circulating levels of hsCRP, IL-1ß, IL-6, and TNF-α in patients with primary restless legs syndrome [RLS] and healthy control subjects. METHODS: We prospectively included 29 patients with primary RLS and 65 healthy controls [HC], all age-sex matched. The diagnosis of RLS was established using international guidelines. IRLSSG Severity Scale was used to evaluate the severity of RLS. Plasma levels of hsCRP, IL-1ß, IL-6, and TNF-α were measured in all participants. RESULTS: The mean age of patients was 37.8 ± 11.3 and 52% of RLS group were women. Serum IL-1ß, IL-6, and TNF-α levels of the patient group were statistically significantly higher compared to HC [p < 0.001 for all variables]. Plasma levels of hsCRP did not differ between groups. There were 8 patients with mild RLS [28%], 13 patients with moderate RLS [45%], and 8 patients with severe RLS [28%]. Only IL-6 values were significantly different between the groups. In the severe group, the value of IL-6 was significantly higher than in the other groups [p: 0.03]. CONCLUSION: These results showing higher circulating levels of inflammatory cytokines in patients with RLS support the notion that inflammation may be involved in the pathogenesis of primary RLS. However, it is necessary to perform further studies to determine if this finding is a cause or an effect.

7.
World J Diabetes ; 11(7): 309-321, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32843933

RESUMO

BACKGROUND: Diabetic polyneuropathy is a very common complication of diabetes. Numerous studies are available in terms of pathogenesis. But examination methods with low reliability are still not standardized and generally time consuming. High-sensitive, easy-to-access methods are expected. Biochemical markers are one of the subjects of research. We aimed to discover a potential biomarker that can be used for this purpose in patients with diabetes who have not yet developed symptoms of neuropathy. AIM: To determine the place and availability of visfatin and thiol-disulfide homeostasis in this disorder. METHODS: A total of 392 patients with type 2 diabetes mellitus were included in the study. The polyneuropathy clinical signs were evaluated with the Subjective Peripheral Neuropathy Screen Questionnaire and Michigan Neuropathy Screening Instrument questionnaire and examination. The biochemical parameters, oxidative stress markers, visfatin, and thiol-disulfide homeostasis were analyzed and correlated with each other and clinical signs. RESULTS: Subjective Peripheral Neuropathy Screen Questionnaire and Michigan Neuropathy Screening Instrument questionnaire with examination scores were correlated with each other and diabetes duration (P < 0.005). Neuropathy related symptoms were present in 20.7% of the patients, but neuropathy related findings were observed in 43.9% of the patients. Serum glucose, glycated hemoglobin, and visfatin were positively correlated with each other. Also, these parameters were positively correlated with the total oxidative stress index. Total and native thiol was positively correlated with total antioxidant status and negatively with oxidant status. Inversely thiol-disulfide positively correlated with higher glucose and oxidant status and negatively with total antioxidant status (P < 0.005). There was no correlation between visfatin and thiol-disulphide (P = 0.092, r = 0.086). However, a significant negative correlation was observed between visfatin and total with native thiol (P < 0.005, r = -0.338), (P < 0.005, r = -0.448). CONCLUSION: Diagnosis of neuropathy is one of the issues studied in patients with diabetes. Visfatin and thiol-disulfide balance were analyzed for the first time in this study with inspiring results.

8.
Curr HIV Res ; 18(5): 354-361, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32652911

RESUMO

BACKGROUND: Serum cytokine levels over the course of HIV infection usually increase with immunosuppression and decrease after antiretroviral treatment (ART). OBJECTIVES: The aim of the study is to compare cytokine levels between HIV-infected patients (HIP) and controls and investigate the relationship between CD4+T cell count, HIV-RNA levels, and cytokine levels. METHODS: The study subjects comprised ART-naive HIP (n=30) with no comorbidities and age-and sex-matched healthy controls. We measured levels of IL-6, IL-1ß, TNF-α, and IFN-γ in serum samples of HIP at the beginning and at month 6 of ART and in controls. RESULTS: The mean age of the study subjects was 38.7 ±10.3 years, with men making up 86.7% of the study subjects (n=26). IL-6, IL-1ß, and TNF-α levels were significantly higher in both ART-naive (p<0.001, p=0.002, p=0.001) and ART-experienced HIP (p<0.001) than controls. The IFN-γ level was lower in both ART-naive and ART-experienced HIP compared to controls (p=0.082 and p=0.002). There was a positive correlation between the CD4+T cell count and serum concentration of IFN- γ(r=0.320, p<0.05). While the serum IFN-γ concentration showed a negative correlation with the HIVRNA level(r=-0.412, p<0.001), the serum IL-1ß, IL-6, and TNF-α concentrations showed a positive correlation with the HIV-RNA level (r=0.349, p<0.001; r:0.54, p<0.001; r:0.438, p<0.00). CONCLUSION: Although serum concentrations of IL-6, IL-1ß and TNF-α showed a significant decrease after ART, they were still significantly higher than the controls. IFN-γ responded differently to ART compared to the other cytokines, indicating that it may play a distinct and important role in the pathogenesis of HIV infection.

9.
Molecules ; 25(14)2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32709059

RESUMO

The concept of hormesis includes a biphasic cellular dose-response to a xenobiotic stimulus defined by low dose beneficial and high dose inhibitory or toxic effects. In the present study, an attempt has been made to help elucidate the beneficial and detrimental effects of thymol on different cell types by evaluating and comparing the impact of various thymol doses on cancerous (AGS) and healthy (WS-1) cells. Cytotoxic, genotoxic, and apoptotic effects, as well as levels of reactive oxygen species and glutathione were studied in both cell lines exposed to thymol (0-600 µM) for 24 h. The results showed significant differences in cell viability of AGS compared to WS-1 cells exposed to thymol. The differences observed were statistically significant at all doses applied (P ≤ 0.001) and revealed hormetic thymol effects on WS-1 cells, whereas toxic effects on AGS cells were detectable at all thymol concentrations. Thymol at low concentrations provides antioxidative protection to WS-1 cells in vitro while already inducing toxic effects in AGS cells. In that sense, the findings of the present study suggest that thymol exerts a dose-dependent hormetic impact on different cell types, thereby providing crucial information for future in vivo studies investigating the therapeutic potential of thymol.

10.
Gastroenterol Res Pract ; 2020: 7386285, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32565785

RESUMO

Objective: This study was designed to investigate the impact of using suture material impregnated with platelet-rich plasma (PRP) in different platelet concentrations on colonic anastomotic wound healing in rats. Methods: A total of 24 Sprague Dawley female rats were separated into 3 groups (n = 8 for each) including the control group (CON; standard vicryl suture repair), the low platelet concentrate PRP group (L-PRP; suture material impregnated with PRP containing average 2.7-fold (range, 2.0 to 3.1) higher amount of platelets vs. control), and the high platelet concentrate PRP group (H-PRP; suture material impregnated with PRP containing average 5.1-fold (range, 4.8 to 5.4) higher amount of platelets vs. control). Rats were sacrificed on the postoperative 7th day for analysis of colonic anastomosis region including macroscopic observation, measurement of anastomotic bursting pressure (ABP), and the hydroxyproline levels and histopathological findings in colon tissue samples. Results: Total injury scores were significantly lower in the L-PRP and H-PRP groups than those in the control group (median (range) 13.00 (7.00) and 11.50 (6.00) vs. 15.50 (4.00), p < 0.05 and p < 0.01, respectively). ABP values (180.00 (49.00) vs. 124.00 (62.00) and 121.00 (57.00) mmHg, p < 0.001 for each) and tissue hydroxyproline levels (0.56 (0.37) vs. 0.25 (0.17) and 0.39 (0.10) µg/mg tissue, p < 0.001 and p < 0.05, respectively) were significantly higher in the L-PRP group as compared with those in the control and H-PRP groups. Conclusion: In conclusion, our findings revealed PRP application to colonic anastomosis sutures to promote the anastomotic healing process. The platelet concentration of PRP seems to have a significant impact on the outcome with superior efficacy of L-PRP over H-PRP in terms of bursting pressures and collagen concentration at the anastomotic site.

11.
Br J Neurosurg ; 34(6): 604-610, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31317782

RESUMO

Background: There is lack of data on the effect of stereotactic radiosurgery in modulation of the immune system for cancer patients with metastatic brain tumours. Therefore, we investigated the change in levels of immunoregulatory molecules after Gamma Knife radiosurgery (GKR) and whole brain radiation therapy (WBRT) in patients with brain metastases.Methods: Peripheral blood samples were collected from 15 patients who received GKR, nine patients who received WBRT for brain metastases and 10 healthy controls. Samples were obtained at three time points such as before, 1h after and 1 week after the index procedure for patients treated with GKR or WBRT. All patients' demographic data and radiosurgical parameters were retrospectively reviewed. We analyzed the change in the levels of T-lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death ligand-1 (PD-L1), and cytokines such as IL-2, IL-10, IFN-γ, TNF-α after GKR and WBRT using Enzyme-linked immunosorbent assays (ELISA).Results: Baseline level of IFN-γ was found to be lower and that of PD-L1 was higher in the GKR group compared to WBRT group and healthy controls (p < 0.05 and p < 0.01, respectively). Levels of IFN-γ and IL-2 were increased (p < 0.01 and p < 0.01, respectively), while CTLA-4 and PD-L1 were decreased (p = 0.05 and p = 0.01, respectively) after GKR compared to pre-GKR levels, while there was no change after WBRT.Conclusion: GKR regulates immunoregulatory molecules towards enhancing the immune system, while WBRT did not exert any effect. These findings suggested that treatment of metastatic brain lesion with GKR might stimulate a systemic immune response against the tumour.

12.
Neurosurg Rev ; 43(6): 1595-1603, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31707576

RESUMO

Neuroinflammation plays an important role in neuronal injury after aneurysmal subarachnoid hemorrhage (aSAH). Sulfonylurea receptor 1 (SUR1) and transient receptor potential cation channel subfamily M member 4 (TRPM4) receptors play an important role in the pathogenesis of several neural injuries, such as neural edema, spinal cord damage, stroke, and neuronal damage in aSAH. This study aimed to investigate the relationship of serum SUR1 and TRPM4 levels with the neurological status within the first 15 days after aSAH. In this prospective study, blood samples were collected from 44 consecutive patients on the 1st, 4th, and 14th days after aSAH. Serum SUR1 and TRPM4 levels were measured using an enzyme-linked immunosorbent assay kit. Glasgow coma scale and World Federation of Neurosurgical Societies (WFNS) scores upon presentation and Glasgow outcome scale (GOS) score on the 14th day were recorded. Serum SUR1 and TRPM4 levels on the 1st, 4th, and 14th days were significantly higher in patients with aSAH than in normal individuals. This increase in the levels varied among the 1st, 4th, and 14th days. On the first day, a correlation was observed between serum SUR1, but not TRPM4, levels and the WFNS score. Moreover, on the 14th day, an association of serum SUR1 and TRPM4 levels with the GOS score was noted. Serum SUR1 and TRPM4 levels were significantly upregulated in the peripheral blood samples. Further study is warranted to establish the utility of SUR1 and TRPM4 as biomarkers in patients with aSAH.

13.
Postepy Dermatol Alergol ; 36(5): 616-619, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31839780

RESUMO

Introduction: Periostin has some effects on the pathogenesis of atopic dermatitis (AD) via release of pro-inflammatory cytokines and chemokines from activated keratinocytes and it is related to chronicity of skin lesions. Aim: To evaluate the relationship between plasma periostin levels and severity and chronicity of AD in children. Material and methods: The study population consisted of 29 children with atopic dermatitis without concomitant allergic disease such as asthma or allergic rhinitis and 31 healthy controls. Data of demographic features, serum eosinophil, total IgE and skin prick test results were collected through the patient's medical records. The severity of the disease was assessed by the SCORAD index. Serum periostin levels were measured with a human periostin ELISA kit. Results: The mean ages of the AD patients and the control group participants were 80.7 ±52.8 and 90.3 ±41.6 months, respectively. Mean plasma periostin levels were 63.0 ±19.0 ng/ml in AD patients, and 23.6 ±7.3 in healthy controls, and there was a statistically significant difference between the two groups (p = 0.001). Plasma periostin level did not vary according to total IgE or serum eosinophil count (p > 0.05). Age of onset and duration of symptoms also were not correlated with plasma periostin levels. Although there was a positive relationship between plasma periostin level and the SCORAD index of patients, it was not statistically significant (r = 0.19, p > 0.05). Conclusions: This study showed that plasma periostin levels were increased in children with atopic dermatitis. Periostin may have a partial role in the pathogenesis of atopic dermatitis, but it is not associated with severity or chronicity in children with atopic dermatitis.

14.
Integr Cancer Ther ; 18: 1534735419876334, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31556752

RESUMO

Many studies have shown that honey with high phenolic contents prevents cancer formation. Furthermore, recent studies have demonstrated that honey can be used for the treatment of cancer as well as cancer prevention. Antineoplastic effects of honey are often associated with their antioxidant phenolic contents. However, very few studies have dealt with the association of phenolic contents of honeys in terms of antiproliferative effects. The aim of this study was, therefore, to elucidate the cytotoxic, genotoxic, apoptotic, and reactive oxygen species (ROS) generating effects of honey samples on the basis of their phenolic and flavonoid contents. Fourteen different honey varieties were collected from various parts of Turkey, and their characteristics regarding total phenols, flavonoids, and antioxidant contents were determined to test their effects on gastric cancer cells (AGS). For convenience, 2 honey varieties were selected, namely, Ida Mountains Quercus pyrenaica honeydew honey (QPHH-IM) having the highest phenolic and antioxidant content and Canakkale multifloral honey (MFH-C) with the lowest phenolic and antioxidant content. Levels of 11 different phenolic compounds in QPHH-IM and MFH-C samples were determined by LC-MS/MS. AGS cells were incubated with different concentrations of QPHH-IM and MFH-C for 24 hours, then the cell viability, DNA damage, apoptosis, and generation of ROS were determined. We found that QPHH-IM had more cytotoxic, genotoxic, and apoptotic effects than that of MFH-C. We think that these effects are probably related to pro-oxidant activities due to the high phenolic contents present. Therefore, further research on high-phenolic honey may contribute to the future development of cancer therapeutics.


Assuntos
Adenocarcinoma/tratamento farmacológico , Apoptose/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Fenóis/farmacologia , Quercus/química , Espécies Reativas de Oxigênio/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/metabolismo , Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Produtos Biológicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Líquida/métodos , Flavonoides/farmacologia , Mel , Humanos , Neoplasias Gástricas/metabolismo , Espectrometria de Massas em Tandem/métodos
15.
World Neurosurg ; 128: e570-e581, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31054338

RESUMO

BACKGROUND: Patients with brain metastasis from melanoma have a dismal prognosis with poor survival time. Gamma Knife (GK) is an effective treatment to control brain metastasis from melanoma. Thymoquinone (TQ) has emerged as a potential therapeutic option due to its antiproliferative effects on various cancers. The purpose of the study was to assess the effect of GK on B16-F10 melanoma cells in vitro and intracerebral melanoma in vivo, and its synergistic effect in combination with TQ. METHODS: The effects of GK and combination treatment of GK and TQ were studied on B16-F10 melanoma cells by evaluating cytotoxicity with an adenosine triphosphate assay, apoptosis by acridine orange staining, and genotoxicity by comet assay. Western blot analysis was performed to investigate the expression of STAT3, p-STAT3 (Tyr705), JAK2, p-JAK2, caspase-3, Bax, Bcl-2, survivin, and ß-actin. Expression of inflammatory cytokines was assessed by enzyme-linked immunosorbent assay. GK alone and in combination with TQ was assessed in an established intracerebral melanoma tumor in mice. RESULTS: The effects of GK on cytotoxicity, genotoxicity, and apoptosis were enhanced by TQ in B16-F10 melanoma cells. GK induced apoptosis through inhibition of p-STAT3 expression, which in turn regulated pro- and antiapoptotic proteins such as caspase-3, Bax, Bcl-2, and survivin. Adding TQ to GK irradiation further enhanced this apoptotic effect of GK irradiation. GK was shown to reduce the levels of tumor-related inflammatory cytokines in B16-F10 melanoma cells. This effect was more pronounced when TQ was added to GK irradiation. GK with 15 Gy increased the survival of mice with intracerebral melanoma compared with untreated mice. However, despite the additive effect of TQ in addition to GK irradiation on B16-F10 melanoma cells in vitro, TQ did not add any significant survival benefit to GK treatment in mice with intracerebral melanoma. CONCLUSIONS: Our findings suggest that TQ would be a potential therapeutic agent in addition to GK to enhance the antitumor effect of irradiation. Further studies are required to support our findings.


Assuntos
Apoptose/efeitos dos fármacos , Benzoquinonas/farmacologia , Neoplasias Encefálicas/terapia , Dano ao DNA/efeitos dos fármacos , Melanoma Experimental/terapia , Radiocirurgia/métodos , Fator de Transcrição STAT3/efeitos dos fármacos , Actinas/efeitos dos fármacos , Actinas/metabolismo , Actinas/efeitos da radiação , Animais , Apoptose/efeitos da radiação , Western Blotting , Neoplasias Encefálicas/secundário , Caspase 3/efeitos dos fármacos , Caspase 3/metabolismo , Caspase 3/efeitos da radiação , Linhagem Celular Tumoral , Terapia Combinada , Dano ao DNA/efeitos da radiação , Técnicas In Vitro , Janus Quinase 2/efeitos dos fármacos , Janus Quinase 2/metabolismo , Janus Quinase 2/efeitos da radiação , Melanoma Experimental/secundário , Camundongos , Fosfoproteínas/efeitos dos fármacos , Fosfoproteínas/metabolismo , Fosfoproteínas/efeitos da radiação , Proteínas Proto-Oncogênicas c-bcl-2/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/efeitos da radiação , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/efeitos da radiação , Survivina/efeitos dos fármacos , Survivina/metabolismo , Survivina/efeitos da radiação , Proteína X Associada a bcl-2/efeitos dos fármacos , Proteína X Associada a bcl-2/metabolismo , Proteína X Associada a bcl-2/efeitos da radiação
16.
Cell Mol Biol (Noisy-le-grand) ; 65(3): 101-108, 2019 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-30942162

RESUMO

Glioblastoma is a malignant tumor of the brain. The treatment of this tumor is still a challenge. Curcumin has been shown to have therapeutic effects when used to treat malignant diseases. However, the molecular mechanisms of its action are not fully elucidated. We hypothesized that reactive oxygen species (ROS) have a key role in curcumin-induced DNA damage, apoptosis, and cell death. To test our hypothesis, cytotoxic, genotoxic, apoptotic, and ROS-generating effects, as well as mitochondrial membrane potentials of curcumin on rat glioma cells (C-6) and normal fibroblastic cells (L-929) were investigated. We examined concentration-dependent cytotoxic, genotoxic, apoptotic, and ROS generating effects of curcumin at C-6 cells and L-929 cells. The cells were incubated with different doses of curcumin (10-100 µM) for 24 hours. Higher doses of curcumin resulted in greater cellular death of cancer than of normal cells at higher concentrations. Curcumin also induced ROS generation in cancer than normal cells in a concentration-dependent manner. Our results showed that curcumin-induced DNA damage in a dose-dependent manner (p < 0.001). At high curcumin concentration such as 80 µM, the proportions of live cells in cancer and normal cell lines were 11.5 and 44.3, respectively. The higher doses of curcumin resulted in greater apoptosis in cancer than normal cells.This in vitro study provided clear evidence that curcumin induced DNA damage and apoptosis. Cytotoxicity may be due to its pro-oxidant activity in a dose-dependent manner in cancer and normal cells. These activities were higher in cancer cells.


Assuntos
Apoptose/efeitos dos fármacos , Neoplasias Encefálicas/patologia , Curcumina/farmacologia , Dano ao DNA , Glioma/patologia , Animais , Anexina A5/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Fluoresceína-5-Isotiocianato , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Ratos , Espécies Reativas de Oxigênio/metabolismo
17.
Andrologia ; 51(8): e13299, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31012132

RESUMO

Oxidative stress causes infertility in men by affecting especially sperm morphology. The aim of the study was to examine the frequencies of paraoxonase-1 (PON1) phenotypes and the serum PON1, arylesterase, total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index, catalase and thiol levels in teratozoospermic infertile men and normospermic fertile men. The study included 184 teratozoospermic infertile men and 72 normospermic fertile men. The double substrate method was employed to determine the phenotype distribution of PON1. The evaluation of sperm morphology was made in accordance with the Kruger's criteria. TAS, catalase and thiol levels were determined to be significantly lower in teratozoospermic infertile men compared to normospermic fertile men. A significant change was not observed in the levels of TOS, PON1 and arylesterase. There was a positive correlation between catalase and thiol levels and sperm morphology. While there were significantly more teratozoospermic men with AA phenotypes compared to normospermic men, there were significantly more persons with AB and BB phenotypes in normospermic men than in teratozoospermic men. As far as we know, such a study was conducted for the first time and suggests that PON1 phenotypic distribution may play a significant role in sterile males because of impaired sperm morphology.


Assuntos
Arildialquilfosfatase/genética , Espermatozoides/patologia , Teratozoospermia/genética , Adulto , Arildialquilfosfatase/sangue , Arildialquilfosfatase/metabolismo , Estudos de Casos e Controles , Voluntários Saudáveis , Humanos , Masculino , Oxidantes/sangue , Estresse Oxidativo , Polimorfismo Genético , Análise do Sêmen , Teratozoospermia/sangue , Teratozoospermia/patologia
18.
Toxicon ; 161: 4-11, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30825463

RESUMO

The aim of this study was to assess anti-inflammatory, anti-oxidant, anti-genotoxic and immunomodulatory effects of honey bee venom (HBV) on adjuvant-induced arthritis in rats. Thirty-five rats were equally divided into a negative control (NC), a positive control (PC) and low, moderate and high doses (2, 4 and 20 mg/kg, respectively) of HBV treatment groups. Freund's Complete Adjuvant (FCA) was given to the rats to form arthritis. The treatment groups were treated with HBV for 3 consecutive weeks. After the treatment, plasma IL-1ß, IL-6, TNF-α, IFN-γ and TGF-ß1, total oxidant status (TOS), total antioxidant status (TAS) and myeloperoxidase (MPO) activities and mononuclear leukocyte (MNL) DNA damage levels were measured. Oxidative stress index (OSI) was calculated. IL-1ß, IL-6, TNF-α, TGF-ß1, IFN-γ, TOS, OSI, DNA damage levels and MPO activities were significantly higher and TAS levels were lower in the PC group than the NC. After low-doses of HBV treatment IL-1ß, IL-6, TNF-α, TGF-ß1, TOS, OSI, MPO and MNL-DNA damage levels significantly decreased according to the PC, while IFN-γ and TAS levels increased. The differences in moderate and high-dose HBV treatment groups were not as significant as low HBV doses. Low-doses of HBV has been shown to treat RA with anti-inflammatory and antioxidant effects, by preventing DNA damage. However, these effects have not been observed as strong at higher doses of HBV. In summary, HBV may be an effective option to ameliorate RA, but the optimization of the therapeutic dose has a crucial role.


Assuntos
Anti-Inflamatórios/farmacologia , Artrite Experimental/tratamento farmacológico , Venenos de Abelha/farmacologia , Animais , Artrite Experimental/induzido quimicamente , Artrite Experimental/metabolismo , Biomarcadores/sangue , Peso Corporal/efeitos dos fármacos , Citocinas/metabolismo , Dano ao DNA , Edema/induzido quimicamente , Adjuvante de Freund , Radical Hidroxila/metabolismo , Leucócitos Mononucleares/efeitos dos fármacos , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar
19.
Cutan Ocul Toxicol ; 38(2): 125-130, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30360657

RESUMO

OBJECTIVE: To compare the possible toxic effects of three light sources used in vitreoretinal endoillumination systems; halogen, xenon, and light-emitting diode (LED) on retinal pigment epithelium (RPE) cell cultures, after two different exposure times. MATERIAL AND METHODS: ARPE-19 human RPE cell cultures were exposed to halogen, xenon, and LED light sources at a distance of 1.5 cm for 30 and 60 min with equal lumen output levels. Cells in the control group were not exposed. RPE cell cultures were compared in terms of cell viability, DNA damage, apoptosis rate, and IL-1ß, IL-6, and TNF- α levels. RESULTS: The halogen light group showed significantly more DNA damage, higher TNF-α, IL-1ß, and IL-6 levels, and lower viable cell count at 30 min compared to the control group. The rates of early and late apoptosis were also significantly higher at 60 min. There were no statistically significant differences in any of the parameters between the xenon and LED light sources and the control group at 30 or 60 min. CONCLUSION: New generation lights, xenon, and LED, seem to be safe in terms of RPE cells. Halogen light may cause toxic effects on RPE cells when used for a long time with maximal power output.


Assuntos
Halogênios/efeitos adversos , Luz/efeitos adversos , Xenônio/efeitos adversos , Apoptose/efeitos da radiação , Linhagem Celular , Citocinas/metabolismo , Dano ao DNA , Células Epiteliais/metabolismo , Células Epiteliais/efeitos da radiação , Humanos , Retina , Pigmentos da Retina
20.
Altern Ther Health Med ; 25(2): 12-21, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29477139

RESUMO

Context: Alternative and complementary medicine has gained importance in anticancer treatment, reflecting a movement toward an integrated approach to treating various diseases. Natural products originating from plants can contain biologically active substances. Thymol is a major component of many plants from the family Lamiaceae that are often used for medicinal and culinary purposes in Mediterranean countries. Objective: The purpose of the present study was to investigate thymol's cytotoxic, genotoxic, apoptotic effects on gastric adenocarcinoma (AGS) cells, including measurement of reactive oxygen species (ROS) and glutathione (GSH) levels at the same time. Design: The research team studied thymol's anticancer potential in vitro. Setting: The research was conducted at the Laboratory of Biochemistry of the Faculty of Medicine at Bezmialem Vakif University (Istanbul, Turkey). Intervention: Caucasian human AGS cells were exposed to 7 concentrations of thymol-10, 20, 30, 50, 100, 200, and 400 µM-prepared from a stock solution of 600 µM of thymol in dimethyl sulfoxide (DMSO), and after 24 h of incubation, the results were analyzed. The thymol was obtained commercially. The study used a negative control prepared in a concentration of 1:1000 from the stock solution of DMSO. Outcome Measures: Cytotoxicity was determined using (1) the adenosine 5'-triphosphate cell viability assay; (2) the dichloro-dihydro-fluorescein diacetate assay to evaluate the generation of ROS; (3) the luminescence-based, total GSH assay to determine the GSH levels; and (4) the comet assay to study genotoxicity. Apoptotic induction of thymol was detected (5) by acridine orange/ethidium bromide staining and (6) by Western blotting using a value below the half maximal inhibitory concentration (IC50). Results: Thymol showed significant cytotoxic, genotoxic, apoptotic, ROS-generating, and GSH-reducing effects, in a dose-dependent manner (P ≤ .001). A close negative relationship existed between cell viability and the ROS level. Conclusions: After researchers have confirmed thymol's anticarcinogenic effects in vitro on healthy cell lines and in vivo, it may be found to be a novel and strong therapeutic agent against gastric cancer. The study's results suggest that thymol may have therapeutic power when developed from natural components of the diet for treatment of the disease.


Assuntos
Adenocarcinoma/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Timol/farmacologia , Adenocarcinoma/patologia , Apoptose , Linhagem Celular Tumoral , Ensaio Cometa , Humanos , Neoplasias Gástricas/patologia , Turquia
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