RESUMO
Although several studies have investigated the cytotoxic effects of different Fabaceae species, limited researches have been conducted on the cytotoxic effect of Dorycnium pentaphyllum. The aim of this study was to evaluate the phenolic characterization and the cytotoxic effect of D. pentaphyllum on human cervix (HeLa) and colon (WiDr) cancer cells and the possible mechanisms involved. Total phenolic content (TPC) and phenolic characterization of the extract were investigated using the Folin-Cioceltau method and RP-HPLC, respectively. The cytotoxic effect of the extract was evaluated using the MTT assay. The mechanism involved in the extract's cytotoxic effect was then evaluated in terms of apoptosis and the cell cycle using flow cytometry, while mitochondrial membrane potential (MMP) was investigated using the fluorometric method. The TPC value of the extract was 141.2 ± 0.8 mg gallic acid equivalent per g sample, and quercetin was detected as major phenolics. D. pentaphyllum extract exhibited a selective cytotoxic effect on HeLa and WiDr cells compared to normal fibroblast and colon cells, respectively. The extract induced cell cycle arrest at the S phase and apoptosis via reduced MMP in these cells. Further studies may be useful in developing a natural product based new generation pharmacological agent.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/patologia , Fabaceae/química , Extratos Vegetais/farmacologia , Neoplasias do Colo do Útero/patologia , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Cromatografia Líquida de Alta Pressão , Feminino , Ácido Gálico/metabolismo , Células HeLa , Humanos , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Fenóis/química , Quercetina/químicaRESUMO
Although several studies have investigated the cytotoxic effects of different Dianthus species, there has been only limited research into the cytotoxic effect of Dianthus carmelitarum. The purpose of this research was to evaluate the phenolic characterization and the cytotoxic effect of D. carmelitarum on human colon cancer (WiDr) cells and the possible mechanisms involved. Total polyphenolic contents (TPC) and phenolic characterization of the extract were evaluated using the Folin-Cioceltau method and reversed-phase high performance liquid chromatography (RP-HPLC), respectively. The cytotoxic activity of the extract was determined using the methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay. The mechanism involved in the extract's cytotoxic effect was then evaluated in terms of apoptosis and the cell cycle using flow cytometry, while mitochondrial membrane potential (MMP) was investigated using the fluorometric method. The TPC value of the extract was 784.8 ± 40.3 mg gallic acid equivalent per 100 g sample, and sinapic acid and benzoic acid were detected as major phenolics in the extract. D. carmelitarum extract exhibited a selective cytotoxic effect (3.6-fold) on WiDr cells compared to normal colon cells. The extract induced cell cycle arrest at the S phase and apoptosis via reduced MMP in WiDr cells. Phytomedical and nutraceutical applications of D. carmelitarum may represent promising approaches in the treatment of cancer.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Dianthus/química , Extratos Vegetais/farmacologia , Pontos de Checagem da Fase S do Ciclo Celular/efeitos dos fármacos , Antineoplásicos Fitogênicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/patologia , Dimetil Sulfóxido/química , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Extratos Vegetais/química , Polifenóis/análiseRESUMO
OBJECTIVE: To compare the effects of alitretionin and isotretionin on endometrial peritoneal implants and serum vascular endothelial growth factor (VEGF) levels. STUDY DESIGN: Forty-eight female Sprague Dawley rats were used. Initially surgical rat endometriosis model was done. The endometrial implant volume was measured and rats were randomly divided into four groups. Group 1: Control group (rats did not get any drug but having endometriotic implants), group 2: rats receiving po isotretionin 10 mg/kg per day for 10 d, group 3: rats receiving po isotretionin 20 mg/kg per day for 10 d and group 4: rats receiving po alitretionin 80 mg/kg per day for 10 d. After 1-week medication, rats were sacrificed and size, histopathology of endometriotic implant and levels of VEGF were evaluated. RESULTS: Volumes of peritoneal endometrial implants were significantly decreased in Group 2 and Group 3 compared with initial values. However, there were no significant changes in histopathological scores and serum VEGF levels in all groups. CONCLUSIONS: This study finding may suggest the possible medical treatment modality of isotretionin on endometriosis. However, alitretionin (potent retinoid) does not have potent regressive effect on endometriotic implants as in isotretionin.
Assuntos
Alitretinoína/uso terapêutico , Endometriose/tratamento farmacológico , Isotretinoína/uso terapêutico , Fator A de Crescimento do Endotélio Vascular/sangue , Alitretinoína/farmacologia , Animais , Avaliação Pré-Clínica de Medicamentos , Feminino , Isotretinoína/farmacologia , Ratos Sprague-DawleyRESUMO
OBJECTIVES: Delayed healing and non-union of fractures have a significant effect upon patient morbidity. Studies have therefore largely concentrated on accelerating fracture healing. This study was intended to compare the effect of "mad honey" and propolis on fracture healing using radiological and histopathological analysis. SUBJECTS AND METHODS: Femur fracture was surgically performed on 48 rats, followed by fixation. Animals were then divided into 8 groups: 2 control groups (15- and 30-day) and 6 treatment groups (15- and 30-day normal honey, 15- and 30-day "mad honey," and 15- and 30-day propolis). Rats were sacrificed at the end of these periods, and radiological and histological examinations were performed. RESULTS: Radiological healing in the propolis group after 15-day therapy was statistically better than in the control (p = 0.004) and normal honey (p = 0.006) groups. After 30-day therapy, healing in the propolis group (p = 0.005) and grayanotoxin-containing "mad honey" group (p = 0.007) were significantly better than in the control group. Histologically, there was a statistically significant difference between the 15-day propolis group and the other groups (control, honey, mad honey: p = 0.003, p = 0.003, and p = 0.002, respectively). We also found a statistically significant difference when the 30-day propolis group (p = 0.005) and "mad honey" group (p = 0.007) were compared to the control group. CONCLUSIONS: This study shows that grayanotoxin-containing "mad honey" and propolis can accelerate fracture healing.
Assuntos
Diterpenos/administração & dosagem , Fraturas do Fêmur/tratamento farmacológico , Consolidação da Fratura/efeitos dos fármacos , Mel , Própole/administração & dosagem , Animais , Modelos Animais de Doenças , Eutanásia Animal , Feminino , Fraturas do Fêmur/diagnóstico por imagem , Fraturas do Fêmur/patologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Ratos , Ratos Sprague-Dawley , Fatores de Tempo , Resultado do TratamentoRESUMO
Many studies have reported cytotoxic effects of different Morus species, but there have been only limited studies on the cytotoxic effect of Morus rubra. The aims of this study were to evaluate the cytotoxic effect of dimethyl sulfoxide extract of M. rubra and to investigate, for the first time, its probable cytotoxic activity in human colon cancer (WiDr) cells, together with the mechanism involved. The cytotoxic activity of extract was determined using MTT assay. The mechanism involved in the cytotoxic effect of extract was then evaluated in terms of apoptosis, and the cell cycle using flow cytometry, mitochondrial membrane potential (MMP) was investigated using the fluorometric method, and expression levels of telomerase and C/EBP homologous protein (CHOP) were investigated using reverse-transcription PCR (RT-PCR). M. rubra extract exhibited moderate selective cytotoxicity on colon cancer cells compared with fibroblast cells. Extract induced cell cycle arrest at the G1 phase and apoptosis via reduced MMP in WiDr cells. Additionally, M. rubra extract significantly repressed telomerase and induced CHOP expressions in WiDr cells. Our results demonstrate that targeting telomerase and endoplasmic reticulum stress represents a promising strategy in colon cancer therapy, and M. rubra may have considerable potential for development as a novel natural product-based anticancer agent.
Assuntos
Neoplasias do Colo/tratamento farmacológico , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Morus/química , Extratos Vegetais/farmacologia , Telomerase/genética , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Cisplatino/farmacologia , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Concentração Inibidora 50 , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Fator de Transcrição CHOP/genéticaRESUMO
Background: Morus nigra L. belongs to the family Moraceae and is frequently used in traditional medicine. Numerous studies have investigated the antiproliferative effects of various extracts of different Morus species, but studies involving the in vitro cytotoxic effect of M. nigra extract are very limited. The purpose of this study was to evaluate the phenolic composition and antioxidant activity of dimethyl sulfoxide extract of M. nigra (DEM) and to investigate, for the first time, the probable cytotoxic effect in human prostate adenocarcinoma (PC-3) cells together with the mechanism involved. Methods: Total polyphenolic contents (TPC), ferric reducing antioxidant power (FRAP) and phenolic compounds of DEM were evaluated using spectrophotometric procedures and HPLC. The cytotoxic effect of DEM on PC-3 cells was revealed using the MTT assay. Mechanisms involved in the cytotoxic effect of DEM on PC-3 cells were then investigated in terms of apoptosis, mitochondrial membrane potential and cell cycle using flow cytometry, while caspase activity was investigated using luminometric analysis. Results: TPC and FRAP values were 20.7 ± 0.3 mg gallic acid equivalents and 48.8 ± 1.6 mg trolox equivalents per g sample, respectively. Ascorbic acid and chlorogenic acid were the major phenolic compounds detected at HPLC analysis. DEM arrested the cell cycle of PC-3 cells at the G1 phase, induced apoptosis via increased caspase activity and reduced mitochondrial membrane potential. Conclusions: Our results indicate that M. nigra may be a novel candidate for the development of new natural product based therapeutic agents against prostate cancer.
RESUMO
BACKGROUND AND OBJECTIVES: Signal peptide-CUB-EGF domain-containing protein 1 (SCUBE1) has been shown to increase in parallel with platelet activation in acute ischaemic and thrombotic diseases. There has been no study evaluating SCUBE1 levels in patients with overt hyperthyroidism (OHyper) and subclinical hyperthyroidism (SHyper), conditions which are known to show impairment of both endothelial and platelet function. This study sought to evaluate SCUBE1 concentrations in patients with SHyper and OHyper, and assessed the effects of antithyroid drug (ATD) therapy on circulating SCUBE1 levels. DESIGN AND METHODS: Forty-five untreated patients with OHyper, 20 untreated patients with SHyper and 30 age- and sex-matched healthy controls were prospectively included in the study. Biochemical and hormonal parameters were evaluated in all patients before and after treatment. RESULTS: Compared with the control subjects, SCUBE1 levels were significantly increased in patients with SHyper and OHyper (P < 0·0001 and P = 0·002, respectively). SCUBE1 levels were not significantly different in patients with OHyper compared with patients with SHyper. There was no significant correlation between serum thyroid hormones and SCUBE1 levels. Plasma SCUBE1 levels decreased significantly in both OHyper and SHyper after ATD treatment (P < 0·05). CONCLUSIONS: Increased SCUBE1 levels in both SHyper and OHyper patients may reflect increased platelet activation and possible endothelial dysfunction, which might augment the risk for atherosclerotic and atherothrombotic complications. SCUBE1 may be used as a reliable marker of endothelial damage in hyperthyroidism, especially in the subclinical period.
Assuntos
Hipertireoidismo/sangue , Proteínas de Membrana/sangue , Adulto , Idoso , Antitireóideos/farmacologia , Antitireóideos/uso terapêutico , Biomarcadores/sangue , Proteínas de Ligação ao Cálcio , Estudos de Casos e Controles , Endotélio Vascular/lesões , Endotélio Vascular/fisiopatologia , Feminino , Humanos , Hipertireoidismo/tratamento farmacológico , Hipertireoidismo/fisiopatologia , Masculino , Proteínas de Membrana/efeitos dos fármacos , Pessoa de Meia-Idade , Ativação Plaquetária , Hormônios Tireóideos/sangueRESUMO
Cancer is a heterogeneous disease, two of whose characteristic features are uncontrollable cell proliferation and insufficient apoptosis. Various studies have investigated the antiproliferative effects of propolis, a natural bee product, from different countries, and its cytotoxic effects have been attributed to its polyphenol contents. The purpose of this study was to show the cytotoxic effects, and possible mechanisms involved, of ethanolic extract of Turkish propolis (EEP) on the human lung cancer (A549) cell line. Cytotoxic activity of EEP on A549 cells was revealed using the MTT assay. Mechanisms involved in the cytotoxic action of EEP on A549 cells were then investigated in terms of apoptosis, mitochondrial membrane potential and cell cycle using flow cytometry, endoplasmic reticulum stress using RT-PCR, and caspase activity using luminometric analysis. EEP exhibited selective toxicity against A549 cells compared to normal fibroblast cells. We determined that EEP arrested the cell cycle of A549 cells at the G1 phase, induced endoplasmic reticulum stress, caspase activity, and apoptosis and reduced mitochondrial membrane potential. These results indicate that Turkish propolis is capable of reducing cancer cell proliferation and may have a promising role to play in the development of new anticancer drugs in the future.
Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias Pulmonares/tratamento farmacológico , Própole/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologiaRESUMO
BACKGROUND AND OBJECTIVES: The main objective of this study was to evaluate the levels of ischemia-modified albumin (IMA) and malondialdehyde (MDA) in patients with subclinical (SHypo) and overt hypothyroidism (OHypo), and to assess the effects of levothyroxine (LT4) therapy on the oxidative stress (OS) parameters. We also investigated the relationships among serum thyroid hormones, lipid parameters, and IMA and MDA in these patients. DESIGN AND METHODS: Thirty untreated patients with OHypo, 25 untreated patients with Shypo, and 30 age- and sex-matched healthy controls were prospectively included in the study. Biochemical and hormonal parameters including IMA and MDA were evaluated in all patients just before and one month after the maintenance of euthyroidism. RESULTS: Compared with the control subjects, the levels of MDA and triglycerides (TG) significantly increased in patients with SHypo (p < 0.001 and p < 0.05, respectively), whereas high density lipoprotein cholesterol (HDL-C) levels significantly decreased (p = 0.01). Patients with OHypo showed significantly high MDA, total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), and TG levels (p = 0.001, p < 0.01, p = 0.01, and p < 0.01, respectively), and significantly low HDL-C levels compared with the controls (p < 0.05). MDA levels and lipid profile were not significantly different in the patients with OHypo when compared with the patients with SHypo. Serum IMA levels did not significantly change in patients with OHypo and SHypo compared with the controls. In the pre-treatment period, MDA levels were inversely correlated with HDL-C levels in patients with OHypo (r: -0.471, p = 0.009). Plasma MDA and LDL-C levels significantly decreased and HDL-C levels significantly increased in the groups of OHypo and SHypo after LT4 treatment. Serum IMA levels did not significantly change with the therapy in all patient groups. CONCLUSIONS: Increased MDA levels in both patient groups represent increased lipid peroxidation which might play an important role in the pathogenesis of the atherosclerosis seen in these patients. Increased OS in patients with SHypo and OHypo could be improved by LT4 treatment. Also, MDA can be used as a reliable marker of OS and oxidative damage, while IMA is considered to be inappropriate.
Assuntos
Terapia de Reposição Hormonal/métodos , Hipotireoidismo , Malondialdeído/sangue , Albumina Sérica , Tiroxina/farmacologia , Adulto , Biomarcadores/sangue , Feminino , Humanos , Hipotireoidismo/sangue , Hipotireoidismo/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/fisiologia , Albumina Sérica/efeitos dos fármacos , Albumina Sérica Humana , Tiroxina/administração & dosagem , Resultado do TratamentoRESUMO
The main purpose of this study was to evaluate the levels of ischemia-modified albumin (IMA) and malondialdehyde (MDA) in patients with OHyper and SHyper, to assess the effects of antithyroid drug (ATD) therapy on the oxidative stress (OS) parameters. Forty-five untreated patients with overt hyperthyroidism (OHyper), 20 untreated patients with subclinical hyperthyroidism (SHyper) and 30 age-and sex-matched healthy controls were prospectively included in the study. Biochemical and hormonal parameters were evaluated in all patients before and after treatment. Compared with the control subjects, the levels of MDA, glucose and TG were significantly increased in patients with SHyper (p<0.05), whereas LDL-C levels were significantly decreased (p<0.01). Patients with OHyper showed significantly elevated MDA and glucose levels (p<0.001) and significantly decreased LDL-C and HDL-C levels compared with the controls (p<0.01). In patients with Graves' disease, serum TSH levels were inversely correlated with plasma MDA levels (r: -0.42, p<0.05). Plasma MDA levels significantly decreased and levels of TC, LDL-C and HDL-C significantly increased in the groups of OHyper and SHyper after treatment. Serum IMA levels did not significantly change at baseline and with the therapy in all subjects. In conclusion, increased MDA levels in both patient groups represent increased lipid peroxidation which might play an important role in the pathogenesis of the atherosclerosis in these patients. Increased oxidative stress in patients with SHyper and OHyper could be improved by ATD therapy. Also, MDA can be used as a reliable marker of OS and oxidative damage, while IMA is considered to be inappropriate.
Assuntos
Antitireóideos/uso terapêutico , Aterosclerose/prevenção & controle , Hipertireoidismo/tratamento farmacológico , Peroxidação de Lipídeos/efeitos dos fármacos , Malondialdeído/sangue , Estresse Oxidativo/efeitos dos fármacos , Adulto , Idoso , Antitireóideos/efeitos adversos , Doenças Assintomáticas/terapia , Aterosclerose/epidemiologia , Aterosclerose/etiologia , Biomarcadores/sangue , Glicemia/análise , Colesterol/sangue , Feminino , Doença de Graves/sangue , Doença de Graves/tratamento farmacológico , Doença de Graves/fisiopatologia , Humanos , Hipertireoidismo/sangue , Hipertireoidismo/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Risco , Albumina Sérica , Albumina Sérica Humana , Tireotropina/sangue , Triglicerídeos/sangue , Turquia/epidemiologiaRESUMO
BACKGROUND: A nationwide multicenter study was organized to establish reference intervals (RIs) in the Turkish population for 25 commonly tested biochemical analytes and to explore sources of variation in reference values, including regionality. METHODS: Blood samples were collected nationwide in 28 laboratories from the seven regions (≥400 samples/region, 3066 in all). The sera were collectively analyzed in Uludag University in Bursa using Abbott reagents and analyzer. Reference materials were used for standardization of test results. After secondary exclusion using the latent abnormal values exclusion method, RIs were derived by a parametric method employing the modified Box-Cox formula and compared with the RIs by the non-parametric method. Three-level nested ANOVA was used to evaluate variations among sexes, ages and regions. Associations between test results and age, body mass index (BMI) and region were determined by multiple regression analysis (MRA). RESULTS: By ANOVA, differences of reference values among seven regions were significant in none of the 25 analytes. Significant sex-related and age-related differences were observed for 10 and seven analytes, respectively. MRA revealed BMI-related changes in results for uric acid, glucose, triglycerides, high-density lipoprotein (HDL)-cholesterol, alanine aminotransferase, and γ-glutamyltransferase. Their RIs were thus derived by applying stricter criteria excluding individuals with BMI >28 kg/m2. Ranges of RIs by non-parametric method were wider than those by parametric method especially for those analytes affected by BMI. CONCLUSIONS: With the lack of regional differences and the well-standardized status of test results, the RIs derived from this nationwide study can be used for the entire Turkish population.
Assuntos
Proteínas Sanguíneas/análise , Testes de Química Clínica , Compostos Inorgânicos/sangue , Lipídeos/sangue , Compostos Orgânicos/sangue , Adulto , Fatores Etários , Idoso , Análise de Variância , Proteínas Sanguíneas/normas , Índice de Massa Corporal , Testes de Química Clínica/normas , Feminino , Humanos , Compostos Inorgânicos/normas , Lipídeos/normas , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Compostos Orgânicos/normas , Valores de Referência , TurquiaRESUMO
OBJECTIVES: The aim of the study was to assess seasonal prevalence of vitamin D deficiency according to sex and to determine the relations between serum levels of 25-hydroxyvitamin D [25(OH)D] and parathyroid hormone (PTH) and sociodemographic characteristics in otherwise healthy schoolchildren during spring and autumn. METHODS: In a cross-sectional study, 746 healthy students aged between 11 and 18 years were recruited during spring (n = 375) and autumn (n = 371). Sociodemographic data were collected by a questionnaire. Serum 25(OH)D, PTH, calcium, phosphate, and alkaline phosphatase were measured. Serum 25(OH)D levels were categorized as <50 nmol/L (vitamin D deficiency) and <25 nmol/L (severe deficiency). RESULTS: Mean ± standard deviation 25(OH)D levels were 22.3 ± 10.5 nmol/L in girls and 28.5 ± 17.0 nmol/L in boys during spring (P < 0.001) and 36.5 ± 20.3 nmol/L in girls and 45.0 ± 18.5 nmol/L in boys during autumn (P < 0.001). The prevalence of vitamin D deficiency was 93% during spring and 71% during autumn. There was a negative correlation between 25(OH)D and PTH levels (P < 0.01). We determined a cutoff point of serum 25(OH)D in which the mean serum PTH concentration began to increase as 35.8 nmol/L (P < 0.0001). The age, sex, and calcium level were found to be independent predictors for vitamin D deficiency. CONCLUSIONS: Vitamin D deficiency is prevalent among healthy schoolchildren. It is noteworthy that 25(OH)D levels were significantly lower in girls and during autumn. We recommend vitamin D supplementation for children in addition to more time spent for outdoor activities for sensible sunlight exposure.
Assuntos
Hormônio Paratireóideo/sangue , Estações do Ano , Deficiência de Vitamina D/epidemiologia , Vitamina D/análogos & derivados , Adolescente , Criança , Estudos Transversais , Suplementos Nutricionais , Exercício Físico , Feminino , Humanos , Masculino , Fatores Sexuais , Luz Solar , Inquéritos e Questionários , Vitamina D/administração & dosagem , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/prevenção & controleRESUMO
Atherosclerosis is one of the most important causes of cardiovascular diseases. A disintegrin and metalloprotease (ADAM)10 and ADAM17 have been identified as important regulators of inflammation in recent years. Our study investigated the effect of inhibiting these enzymes with selective inhibitor and propolis on atherosclerosis. In our study, C57BL/6J mice (n = 16) were used in the control and sham groups. In contrast, ApoE-/- mice (n = 48) were used in the case, water extract of propolis (WEP), ethanolic extract of propolis (EEP), GW280264X (GW-synthetic inhibitor), and solvent (DMSO and ethanol) groups. The control group was fed a control diet, and all other groups were fed a high-cholesterol diet for 16 weeks. WEP (400 mg/kg/day), EEP (200 mg/kg/day), and GW (100 µg/kg/day) were administered intraperitoneally for the last four weeks. Animals were sacrificed, and blood, liver, aortic arch, and aortic root tissues were collected. In serum, total cholesterol (TC), triglycerides (TGs), and glucose (Glu) were measured by enzymatic colorimetric method, while interleukin-1ß (IL-1ß), paraoxonase-1 (PON-1), and lipoprotein-associated phospholipase-A2 (Lp-PLA2) were measured by ELISA. Tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), myeloperoxidase (MPO), interleukin-6 (IL-6), interleukin-10 (IL-10), and interleukin-12 (IL-12) levels were measured in aortic arch by ELISA and ADAM10/17 activities were measured fluorometrically. In addition, aortic root and liver tissues were examined histopathologically and immunohistochemically (ADAM10 and sortilin primary antibody). In the WEP, EEP, and GW groups compared to the case group, TC, TG, TNF-α, IL-1ß, IL-6, IL-12, PLA2, MPO, ADAM10/17 activities, plaque burden, lipid accumulation, ADAM10, and sortilin levels decreased, while IL-10 and PON-1 levels increased (p < 0.003). Our study results show that propolis can effectively reduce atherosclerosis-related inflammation and dyslipidemia through ADAM10/17 inhibition.
Assuntos
Proteína ADAM10 , Secretases da Proteína Precursora do Amiloide , Dislipidemias , Inflamação , Camundongos Endogâmicos C57BL , Própole , Animais , Proteína ADAM10/metabolismo , Própole/farmacologia , Inflamação/prevenção & controle , Dislipidemias/tratamento farmacológico , Dislipidemias/etiologia , Camundongos , Masculino , Secretases da Proteína Precursora do Amiloide/metabolismo , Aterosclerose/prevenção & controle , Aterosclerose/etiologia , Colesterol na Dieta/efeitos adversos , Dieta Hiperlipídica/efeitos adversos , Proteínas de Membrana/metabolismo , Modelos Animais de DoençasRESUMO
BACKGROUND: Cervical cancer has been ranked as the fourth most common cancer in women. The role of HPV, the DNA virus identified in the 1980s, in almost all cervical cancers is undisputed. In patients scanned with smear and HPV, a cervical biopsy is performed accompanied by colposcopic examination, and the lesion is defined. The concentration of mucoproteins varies in the structure of the cervical mucus with neoplasms. The major aim of this study was to investigate the changes in the levels of cervical mucoprotein in patients at the early stages of cervical cancer and evaluate if these levels can be used in the early diagnosis of this cancer type. METHODS: The study was designed as a prospective cohort study. Samples from cervical mucus were taken and stored before colposcopy examination of human papillomavirus (HPV) positive patients (N.=100). According to the pathology results, while 36 cases constituted the precancerous group, no suspicion of cancer was found in 64 cases. To ensure standardization, colposcopy was performed immediately after the menstrual cycle and at least 0.5 mL of the cervical mucus sample was taken from all individual patients used in this study. Cervical mucus samples of the patients were analyzed for mucoproteins MUC1, MUC2, MUC5AC and MUC5B. RESULTS: All mucoprotein levels were found to be higher in patients with cervical intraepithelial neoplasia (CIN) than those of subjects with normal pathology for cervical neoplasia. CONCLUSIONS: Significant relationship was obtained between cervical intraepithelial neoplasms and the levels of mucoproteins in cervical mucus. The results showed that diagnosis of neoplasia with HPV may be easily performed by utilizing any mucoprotein test.
Assuntos
Infecções por Papillomavirus , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/patologia , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/diagnóstico , Estudos Prospectivos , Colo do Útero/patologia , Displasia do Colo do Útero/diagnóstico , Displasia do Colo do Útero/patologiaRESUMO
Heparin induces apoptosis on peripheral neutrophils, mononuclear cells of the healthy controls, and on lymphoblasts of the patients with acute lymphoblastic leukemia, in vitro. We studied the caspase-9 activity and cytochrome C level as the indicators of the apoptotic effect of heparin on lymphoblasts by the intrinsic pathway of apoptosis. Twenty samples of the patients with acute lymphoblastic leukemia were included in the study. Cytochrome C level and caspase-9 activity were concomitantly determined with the percentage of apoptotic lymphoblasts when incubated in 0, 10, and 20 U/mL heparin concentrations at 0, 1, and 2 hours. The percentages of apoptosis of lymphoblasts at the first hour were higher than those at 0 and 2 hours in 10 and 20 U/mL heparin concentrations, separately (P<0.05). The mean percentage of apoptosis of lymphoblasts in 20 U/mL heparin levels was significantly higher than those in 0 and 10 U/mL heparin levels at 1 and 2 hours (P<0.05). The highest apoptotic effect of heparin on lymphoblasts was determined at the first hour in 20 U/mL heparin concentration. The mean caspase-9 activitity at the first hour was significantly higher than the values at 0 and 2 hours in 10 and 20 U/mL heparin levels, separately (P<0.05). The mean caspase-9 activity in 20 U/mL heparin concentration was significantly higher than values in 0 and 10 U/mL heparin concentrations at 1 and 2 hours (P<0.05). The highest caspase-9 activity was determined in 20 U/mL heparin levels at the first hour. The mean cytochrome C level at the first hour was significantly higher than those at 0 and 2 hours in 10 and 20 U/mL heparin concentrations, separately (P<0.05). The highest cytochrome C level was determined in 20 U/mL heparin concentration at the first hour. We claimed that heparin induces the apoptosis of lymphoblasts by the activation of the intrinsic pathway.
Assuntos
Apoptose/efeitos dos fármacos , Caspase 9/metabolismo , Citocromos c/análise , DNA/análise , Citometria de Fluxo/métodos , Heparina/farmacologia , Linfócitos/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ativação Enzimática/efeitos dos fármacos , Humanos , Linfócitos/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologiaRESUMO
There is some evidence that an immune response with an increased production of proinflammatory cytokines frequently accompanies major depression. The aim of this study was to determine the serum levels of interleukines (IL-1ß, IL-6, IL-8, IL-10), tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ) and immonuglobulines (IgG, IgA and IgM) levels and to examine the relationships between all above parameters and lipid parameters. The study group included 30 patients and 30 healthy volunteers. Although total cholesterol, HDL-cholesterol, and IgM levels were increased significantly (p < 0.05) in patients and compared to those of the controls, no statistically significant differences (p > 0.05) were observed with other parameters. IFN-γ were positively correlated with total cholesterol (r = 0.425; P = 0.019) and LDL-cholesterol (r = 0.391; P = 0.032) levels in patients. Other cytokines and immunoglobulins did not show any correlation with lipid parameters. It was concluded that although no differences was observed in cytokines and immunoglobulin levels in the present study, the dysregulation of the lipids and immune system including the cytokine network is associated with the etiology and pathophysiology of major depressive disorders.
Assuntos
Citocinas/metabolismo , Transtorno Depressivo Maior/metabolismo , Metabolismo dos Lipídeos/fisiologia , Adulto , Fatores Etários , Glicemia/metabolismo , Colesterol/sangue , Feminino , Humanos , Imunoglobulina A/metabolismo , Imunoglobulina G/metabolismo , Imunoglobulina M/metabolismo , Interferon gama/metabolismo , Interleucina-10/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , Triglicerídeos/sangue , Fator de Necrose Tumoral alfa/metabolismoRESUMO
OBJECTIVE: The objectives of this study were to determine the prevalence of diagnosed and undiagnosed diabetes mellitus (DM) and prediabetes, and to evaluate the associated risk factors in a sample of adult Turkish population. METHODS: A total of 4000 eligible study subjects, aged 20 years or older, chosen by multistage sampling on a field were considered. Of those 3721 subjects (2139 women and 1582 men) participated in the study. RESULTS: The prevalence of prediabetes and DM were found to be as 6.4% and 10.4% (3.6% being newly diagnosed by this study), respectively. In multivariate logistic regression analysis, advanced age (OR:26.7, p < 0.0005 in the group 70 years and over), marriage (OR:2.05, p = 0.047), housewives (OR:1.34, p = 0.003), family history of diabetes (OR:2.84, p < 0.0005), overweight (OR:1.61, p = 0.026), obesity (OR:2.25, p < 0.0005), hypertension (OR:1.42, p = 0.007) and dyslipidemia (OR:1.38, p = 0.028) were independent risk factors for being diabetic. CONCLUSIONS: DM is an important health problem in the adult population of Trabzon city. Newly diagnosed diabetic patients who were unaware of their status are at high risk. To control DM and associated risk factors, effective public health education and taking urgent steps are needed.
Assuntos
Diabetes Mellitus , Hipertensão , Estado Pré-Diabético , Adulto , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Masculino , Estado Pré-Diabético/diagnóstico , Estado Pré-Diabético/epidemiologia , Prevalência , Fatores de RiscoRESUMO
BACKGROUND: Propolis is a natural, resinous hive product that has several pharmacological activities. Its composition varies depending on the vegetation, climate, season and environmental conditions of the area from where it was collected. Surface enhanced laser desorption ionization time of flight mass spectrometry (SELDI-TOF MS) is a proteomic approach which has been used in cancer proteomics studies. Prostate cancer is one of the most commonly diagnosed cancers in men. It has shown that nutritional supplements rich in polyphenolic compounds such as propolis play a significant role in prostate cancer chemoprevention. The aim of this study is to evaluate if protein expression profile in PC-3 prostate cancer cell lines could be differentiated when incubated with dimethyl sulfoxide and water extracts of Turkish propolis. RESULTS: The antioxidant potentials of dimethyl sulfoxide and water extracts of propolis were found in correlation with the amount of total phenolic compounds of them. Dimethyl sulfoxide and water extracts of propolis of 20 µg/mL reduced the cell viability to 24.5% and 17.7%, respectively. Statistically significant discriminatory peaks between control PC-3 cells and dimethyl sulfoxide extract of propolis-treated PC-3 cells were found to be the proteomic features at m/z 5143, 8703, 12661, 20184 and 32794, detected by CM10 ProteinChip, and the peak at m/z 3772, detected by Q10 ProteinChip. Between control PC-3 cells and water extract of propolis-treated PC-3 cells, statistically significant discriminatory peaks were found to be the proteomic features at m/z 15846, 16052 and 24658, detected by CM10 ProteinChip and the peaks at m/z 10348, 10899 and 11603, detected by Q10 ProteinChip. CONCLUSIONS: It was concluded that dimethyl sulfoxide and water extracts of Turkish propolis may have anti-proliferative activity through differentiating protein expression profile in PC-3 prostate cancer cell lines along with their antioxidant capacity.
RESUMO
Antiepileptic drugs (AED) had an effect on bone metabolism in children. This study was conducted in order to determine the relationships between serum leptin levels, bone mineral density (BMD) and bone turnover markers in epileptic children. Fifty-three patients were treated with valproic acid (VPA) and 23 with carbamazepine (CBZ) monotherapy; 50 healthy children were included in the study as controls. Serum alkaline phosphatase (ALP) and cross-linked C-telopeptide (CTx) levels were statistically significantly higher in the CBZ group than in the VPA group and the control group (p < 0.0001, p < 0.010, respectively). Serum osteocalcin and ALP levels were significantly lower in the VPA group than in the control group (P < 0.012, P < 0.030, respectively). Although we found slightly higher serum leptin levels in both the CBZ and VPA groups, they were not significantly different from the control group (P > 0.05). We demonstrated that the markers of bone formation and resorption increased with CBZ and decreased with VPA treatment without affecting BMD and vitamin D levels in prepubertal epileptic children.
Assuntos
Anticonvulsivantes/uso terapêutico , Remodelação Óssea/efeitos dos fármacos , Epilepsia/tratamento farmacológico , Epilepsia/metabolismo , Leptina/sangue , Ácido Valproico/uso terapêutico , Biomarcadores/sangue , Densidade Óssea/efeitos dos fármacos , Carbamazepina/uso terapêutico , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , MasculinoRESUMO
AIM: To date, various molecules have been investigated to reduce the effect of renal ischemia/reperfusion (I/R) injury. However, none have yet led to clinical use. The present study aimed to investigate the protective effect of cordycepin (C) on renal I/R injury in an experimental rat model. MATERIALS AND METHODS: Twenty-four mature Sprague Dawley female rat was randomly divided into three groups: Sham, I/R, I/R+C. All animals underwent abdominal exploration. To induce I/R injury, an atraumatic vascular bulldog clamp was applied to the right renal pedicle for 60 minutes (ischemia) and later clamp was removed to allow reperfusion in all rats, except for the sham group. In the I/R + C group, 10 mg/kg C was administered intraperitoneally, immediately after reperfusion. After 4 hours of reperfusion, the experiment was terminated with right nephrectomy. Histological studies and biochemical analyses were performed on the right nephrectomy specimens. EGTI (endothelial, glomerular, tubulointerstitial) histopathology scoring and semi-quantitative analysis of renal cortical necrosis were used for histological analyses and superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), total oxidant status (TOS) for biochemical analyses. RESULTS: Histopathological examination of the tissue damage revealed that all kidneys in the sham group were normal. The I/R group had higher histopathological scores than the I/R + C group. In the biochemical analysis of the tissues, SOD, MDA, TOS values were found to be statistically different in the I/R group compared to the I/R + C group (p: 0.004, 0.004, 0.001 respectively). CONCLUSIONS: Intraperitoneal cordycepin injection following ischemia preserve renal tissue against oxidative stress in a rat model of renal I/R injury.