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1.
J Appl Clin Med Phys ; 24(2): e13879, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36546569

RESUMO

Nanoscopic lesions (complex damages), are the most lethal lesions for the cells. As nanoparticles have become increasingly popular in radiation therapy and the importance of analyzing nanoscopic dose enhancement has increased, a reliable tool for nanodosimetry has become indispensable. In this regard, the DNA plasmid is a widely used tool as a nanodosimetry probe in radiobiology and nano-radiosensitization studies. This approach is helpful for unraveling the radiosensitization role of nanoparticles in terms of physical and physicochemical effects and for quantifying radiation-induced biological damage. This review discusses the potential of using plasmid DNA assays for assessing the relative effects of nano-radiosensitizers, which can provide a theoretical basis for the development of nanoscopic biodosimetry and nanoparticle-based radiotherapy.


Assuntos
Nanopartículas Metálicas , Radiossensibilizantes , Humanos , Radiobiologia , DNA , Plasmídeos
2.
Cancer Cell Int ; 22(1): 257, 2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-35971151

RESUMO

Over the past few years, the cancer-related disease has had a high mortality rate and incidence worldwide, despite clinical advances in cancer treatment. The drugs used for cancer therapy, have high side effects in addition to the high cost. Subsequently, to reduce these side effects, many studies have suggested the use of natural bioactive compounds. Among these, which have recently attracted the attention of many researchers, quercetin has such properties. Quercetin, a plant flavonoid found in fresh fruits, vegetables and citrus fruits, has anti-cancer properties by inhibiting tumor proliferation, invasion, and tumor metastasis. Several studies have demonstrated the anti-cancer mechanism of quercetin, and these mechanisms are controlled through several signalling pathways within the cancer cell. Pathways involved in this process include apoptotic, p53, NF-κB, MAPK, JAK/STAT, PI3K/AKT, and Wnt/ß-catenin pathways. In addition to regulating these pathways, quercetin controls the activity of oncogenic and tumor suppressor ncRNAs. Therefore, in this comprehensive review, we summarized the regulation of these signalling pathways by quercetin. The modulatory role of quercetin in the expression of various miRNAs has also been discussed. Understanding the basic anti-cancer mechanisms of these herbal compounds can help prevent and manage many types of cancer.

3.
Virol J ; 19(1): 92, 2022 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-35619180

RESUMO

Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has posed a significant threat to global health. This virus affects the respiratory tract and usually leads to pneumonia in most patients and acute respiratory distress syndrome (ARDS) in 15% of cases. ARDS is one of the leading causes of death in patients with COVID-19 and is mainly triggered by elevated levels of pro-inflammatory cytokines, referred to as cytokine storm. Interleukins, such as interleukin-6 (1L-6), interleukin-1 (IL-1), interleukin-17 (IL-17), and tumor necrosis factor-alpha (TNF-α) play a very significant role in lung damage in ARDS patients through the impairments of the respiratory epithelium. Cytokine storm is defined as acute overproduction and uncontrolled release of pro-inflammatory markers, both locally and systemically. The eradication of COVID-19 is currently practically impossible, and there is no specific treatment for critically ill patients with COVID-19; however, suppressing the inflammatory response may be a possible strategy. In light of this, we review the efficacy of specific inhibitors of IL6, IL1, IL-17, and TNF-α for treating COVID-19-related infections to manage COVID-19 and improve the survival rate for patients suffering from severe conditions.


Assuntos
COVID-19 , Síndrome do Desconforto Respiratório , COVID-19/complicações , Síndrome da Liberação de Citocina , Humanos , Interleucina-17 , Interleucina-6 , Pulmão/patologia , SARS-CoV-2 , Fator de Necrose Tumoral alfa
4.
Microrna ; 11(2): 95-103, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35507794

RESUMO

In eukaryotic organisms such as humans, some noncoding single-stranded RNAs (ncRNAs) contribute to regulating the expression of some genes before and after the transcription process, which in turn controls a number of vital physiological processes, including cell proliferation, differentiation, invasion, angiogenesis, and embryonic development. miR-126 is one of these miRNAs expressed exclusively in endothelial cells such as capillaries and vessels involved in controlling angiogenesis. In recent years, the link between miRs such as miR-126 and the pathology of breast cancer has attracted the attention of many researchers. Numerous studies have shown that miR-126 may be able to suppress tumor tissue metastasis or to increase tumor metastasis through complex molecular mechanisms. There is ample clinical evidence that miR-126 can be used as a biomarker to predict and diagnose breast cancer due to the increased or decreased expression of certain genes in breast cancer tissue. In this review, we discuss the association between the growth and metastasis (tumorigenesis) of breast cancer and miR-126, as well as the relationship between current research advances in the prognosis, diagnosis, and treatment of breast cancer and miR-126.


Assuntos
Neoplasias da Mama , MicroRNAs , Humanos , Feminino , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , MicroRNAs/genética , Prognóstico , Células Endoteliais/metabolismo , Proliferação de Células/genética , Neovascularização Patológica/genética
5.
BMC Med Genomics ; 15(1): 18, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-35101039

RESUMO

BACKGROUND: Hereditary hearing loss (HHL) is a common heterogeneous disorder affecting all ages, ethnicities, and genders. The most common form of HHL is autosomal recessive non-syndromic hearing loss (ARNSHL), in which there is no genotype-phenotype correlation in the majority of cases. This study aimed to identify the genetic causes of hearing loss (HL) in a family with Iranian Azeri Turkish ethnicity negative for gap junction beta-2 (GJB2), gap junction beta-6 (GJB6), and mitochondrially encoded 12S rRNA (MT-RNR1) deleterious mutations. METHODS: Targeted genome sequencing method was applied to detect genetic causes of HL in the family. Sanger sequencing was employed to verify the segregation of the variant. Finally, we used bioinformatics tools and American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines to determine whether the detected variant might affect the corresponding protein or not. RESULTS: A novel homozygous missense mutation, c.499G>A (p.G167R), was identified in exon 5 of the ESRRB (estrogen-related receptor beta) gene. Healthy and affected family members confirmed the co-segregation of the variant with ARNSHL. Eventually, the variant's pathogenicity was confirmed by the in silico analysis and the ACMG/AMP guidelines. CONCLUSION: The study suggests that the detected variant, c.499G>A, plays a crucial role in the development of ARNSHL, emphasizing the clinical significance of the ESRRB gene in ARNSHL patients. Additionally, it would be helpful for genetic counseling and clinical management of ARNSHL patients and providing preventive opportunities.


Assuntos
Surdez , Perda Auditiva Neurossensorial , Perda Auditiva , Conexinas/genética , Surdez/genética , Feminino , Perda Auditiva/genética , Perda Auditiva Neurossensorial/genética , Humanos , Irã (Geográfico) , Masculino , Mutação , Mutação de Sentido Incorreto , Linhagem , Receptores de Estrogênio
6.
J Transl Med ; 20(1): 30, 2022 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-35033106

RESUMO

Clinical oncologists need more reliable and non-invasive diagnostic and prognostic biomarkers to follow-up cancer patients. However, the existing biomarkers are often invasive and costly, emphasizing the need for the development of biomarkers to provide convenient and precise detection. Extracellular vesicles especially exosomes have recently been the focus of translational research to develop non-invasive and reliable biomarkers for several diseases such as cancers, suggesting as a valuable source of tumor markers. Exosomes are nano-sized extracellular vesicles secreted by various living cells that can be found in all body fluids including serum, urine, saliva, cerebrospinal fluid, and ascites. Different molecular and genetic contents of their origin such as nucleic acids, proteins, lipids, and glycans in a stable form make exosomes a promising approach for various cancers' diagnoses, prediction, and follow-up in a minimally invasive manner. Since exosomes are used by cancer cells for intercellular communication, they play a critical role in the disease process, highlighting the importance of their use as clinically relevant biomarkers. However, regardless of the advantages that exosome-based diagnostics have, they suffer from problems regarding their isolation, detection, and characterization of their contents. This study reviews the history and biogenesis of exosomes and discusses non-coding RNAs (ncRNAs) and their potential as tumor markers in different types of cancer, with a focus on next generation sequencing (NGS) as a detection method. Moreover, the advantages and challenges associated with exosome-based diagnostics are also presented.


Assuntos
Exossomos , Vesículas Extracelulares , Neoplasias , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Exossomos/genética , Exossomos/metabolismo , Vesículas Extracelulares/metabolismo , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Neoplasias/diagnóstico , Neoplasias/genética , Neoplasias/metabolismo
7.
Microrna ; 10(3): 181-190, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34514995

RESUMO

MicroRNAs (miRNAs) are highly conserved non-coding RNAs involved in many physiological processes such as cell proliferation, inhibition, development of apoptosis, differentiation, suppression of tumorigenicity, and regulation of cell growth. The description of the alterations of miRNA expression patterns in cancers will be helpful in recognizing biomarkers for early detection and possible therapeutic intervention in the treatment of cancers. Recent studies have shown that miR-451 is broadly dysregulated in lung cancer and is a crucial agent in lung tumor progression. This review summarizes recent advances in the potential role of miR-451 in lung cancer diagnosis, prognosis, and treatment and provides an insight into the potential use of miR-451 for the development of advanced therapeutic methods in lung cancer.


Assuntos
Neoplasias Pulmonares , MicroRNAs , Apoptose/genética , Biomarcadores , Biomarcadores Tumorais/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , MicroRNAs/genética
8.
Oxid Med Cell Longev ; 2021: 3157867, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34381559

RESUMO

Lymphoma is a name for malignant diseases of the lymphatic system including Hodgkin's lymphoma and non-Hodgkin's lymphoma. Although several approaches are used for the treatment of these diseases, some of them are not successful and have serious adverse effects. Therefore, other effective treatment methods might be interesting. Studies have indicated that plant ingredients play a key role in treating several diseases. Some plants have already shown a potential therapeutic effect on many malignant diseases. Quercetin is a flavonoid found in different plants and could be useful in the treatment of different malignant diseases. Quercetin has its antimalignant effects through targeting main survival pathways activated in tumor cells. In vitro/in vivo experimental studies have demonstrated that quercetin possesses a cytotoxic effect on lymphoid cancer cells. Regardless of the optimum results that have been obtained from both in vitro/in vivo studies, few clinical studies have analyzed the antitumor effects of quercetin in lymphoid cancers. Thus, it seems that more clinical studies should introduce quercetin as a therapeutic, alone or in combination with other chemotherapy agents. Here, in this study, we reviewed the anticancer effects of quercetin and highlighted the potential therapeutic effects of quercetin in various types of lymphoma.


Assuntos
Antineoplásicos/farmacologia , Linfoma/tratamento farmacológico , Quercetina/farmacologia , Animais , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Humanos , Linfoma/metabolismo , Quercetina/uso terapêutico , Transdução de Sinais/efeitos dos fármacos
9.
Gene ; 804: 145894, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34418469

RESUMO

Colorectal cancer (CRC) is the third most frequent cancer in human beings and is also the major cause of death among the other gastrointestinal cancers. The exact mechanisms of CRC development in most patients remains unclear. So far, several genetically, environmental and epigenetically risk factors have been identified for CRC development. The circadian rhythm is a 24-h rhythm that drives several biologic processes. The circadian system is guided by a central pacemaker which is located in the suprachiasmatic nucleus (SCN) in the hypothalamus. Circadian rhythm is regulated by circadian clock genes, cytokines and hormones like melatonin. Disruptions in biological rhythms are known to be strongly associated with several diseases, including cancer. The role of the different circadian genes has been verified in various cancers, however, the pathways of different circadian genes in the pathogenesis of CRC are less investigated. Identification of the details of the pathways in CRC helps researchers to explore new therapies for the malignancy.


Assuntos
Relógios Circadianos/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Encéfalo/metabolismo , Ritmo Circadiano/genética , Neoplasias Colorretais/metabolismo , Humanos , Hipotálamo/metabolismo , Melatonina/metabolismo , Proteínas Circadianas Period/genética
10.
BMC Microbiol ; 21(1): 218, 2021 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-34281519

RESUMO

BACKGROUND: Colorectal cancer which is related to genetic and environmental risk factors, is among the most prevalent life-threatening cancers. Although several pathogenic bacteria are associated with colorectal cancer etiology, some others are considered as highly selective therapeutic agents in colorectal cancer. Nowadays, researchers are concentrating on bacteriotherapy as a novel effective therapeutic method with fewer or no side effects to pay the way of cancer therapy. The introduction of advanced and successful strategies in bacterial colorectal cancer therapy could be useful to identify new promising treatment strategies for colorectal cancer patients. MAIN TEXT: In this article, we scrutinized the beneficial effects of bacterial therapy in colorectal cancer amelioration focusing on different strategies to use a complete bacterial cell or bacterial-related biotherapeutics including toxins, bacteriocins, and other bacterial peptides and proteins. In addition, the utilization of bacteria as carriers for gene delivery or other known active ingredients in colorectal cancer therapy are reviewed and ultimately, the molecular mechanisms targeted by the bacterial treatment in the colorectal cancer tumors are detailed. CONCLUSIONS: Application of the bacterial instrument in cancer treatment is on its way through becoming a promising method of colorectal cancer targeted therapy with numerous successful studies and may someday be a practical strategy for cancer treatment, particularly colorectal cancer.


Assuntos
Fenômenos Fisiológicos Bacterianos , Neoplasias Colorretais/terapia , Bactérias/genética , Bactérias/metabolismo , Neoplasias Colorretais/microbiologia , Sistemas de Liberação de Medicamentos , Técnicas de Transferência de Genes , Humanos
11.
Immunopharmacol Immunotoxicol ; 42(6): 632-642, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33081532

RESUMO

AIM: The imbalance of Th17/Treg cells has been recently suggested as a new risk factors for recurrent implantation failure (RIF). Furthermore Th17/Treg cells are involved in immune regulation in peripheral blood and endometrial tissue of patients with RIF. In this research, we investigated the effects of Hydroxychloroquine (HCQ) on the level and function of Th17 and Treg cells in women with RIF. It may be possible to improve pregnancy outcomes by modulating high cytokine levels. METHODS: Women with RIF received oral HCQ (n = 60) on day 4 of the menstrual cycle and continued until day 20 of the menstrual cycle and 2 days before embryo transfer and continued until the day of the pregnancy test, for a total of 16 days in another cycle. The serum levels of IL-17 and IL-10, the expression of transcription factors related to Th17 and Treg cells and the immune-reactivity of IL-17, IL-21 as Th17 related cytokines and IL-10, TGF- ß as Treg related cytokines in endometrial tissues were evaluated by ELISA, real-time PCR, and fluorescent immunohistochemistry respectively.Results: Treatment with HCQ down-regulated Th17 related cytokines and function and up-regulated Treg related cytokines and function significantly (p < .001). RORγt, the Th17 transcription factor, expression was down-regulated and FOXP-3, the T-reg transcription factor, expression was up-regulated. The biochemical pregnancy rate was not significantly different in RIF patients before and after treatment. CONCLUSION: Our results demonstrated that the administration of HCQ in RIF women with immune cell disorders during pregnancy could affect the Th17/Treg ratio and enhance Treg and diminish Th17 responses which may be associated with successful pregnancy outcomes. However, significant difference in pregnancy outcomes was not observed in the present study.


Assuntos
Implantação do Embrião/efeitos dos fármacos , Transferência Embrionária , Endométrio/efeitos dos fármacos , Hidroxicloroquina/uso terapêutico , Fatores Imunológicos/uso terapêutico , Infertilidade/tratamento farmacológico , Linfócitos T Reguladores/efeitos dos fármacos , Células Th17/efeitos dos fármacos , Adulto , Contagem de Linfócito CD4 , Citocinas/sangue , Transferência Embrionária/efeitos adversos , Endométrio/imunologia , Endométrio/metabolismo , Endométrio/fisiopatologia , Feminino , Fertilização in vitro , Fatores de Transcrição Forkhead/metabolismo , Humanos , Hidroxicloroquina/efeitos adversos , Fatores Imunológicos/efeitos adversos , Infertilidade/sangue , Infertilidade/imunologia , Infertilidade/fisiopatologia , Irã (Geográfico) , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Gravidez , Taxa de Gravidez , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Células Th17/imunologia , Células Th17/metabolismo , Fatores de Tempo , Resultado do Tratamento
12.
Geburtshilfe Frauenheilkd ; 80(8): 851-862, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32817992

RESUMO

Introduction An abnormal endometrial immune response is involved in the pathogenesis of repeated implantation failure (RIF), so we investigated the effectiveness of tacrolimus treatment on the endometrium of RIF patients. Materials and Methods Ten RIF patients with elevated T-helper 1/T-helper 2 (Th1/Th2) cell ratios were recruited into a clinical study. The expression of p53, leukemia inhibitory factor (LIF), interleukin (IL)-4, IL-10, IL-17, and interferon gamma (IFN-γ) in the endometrium of patients with and without tacrolimus treatment and the association of these factors with assisted reproductive technology (ART) outcomes were investigated. Results Tacrolimus significantly increased the expression of LIF, IL-10, and IL-17 and decreased the expression of IL-4, IFN-γ, and the IFN-γ/IL-10 ratio in RIF patients. Tacrolimus treatment resulted in an implantation rate of 40%, a clinical pregnancy rate of 50%, and a live birth rate of 35% in RIF patients with elevated Th1/Th2 ratios who had previously failed to become pregnant despite at least three transfers of embryos. We also found a significant positive correlation between IL-10 levels and the implantation rate. Conclusions Our findings suggest that RIF patients with a higher Th1/Th2 ratio could be candidates for tacrolimus therapy and that this immunosuppressive drug could be acting through upregulation of LIF, IL-10, and IL-17.

13.
Int. braz. j. urol ; 45(4): 825-833, July-Aug. 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1019889

RESUMO

ABSTRACT Purpose No comprehensive information is available about uterus fatty acid (FA) change during implantation period and possible effects of the seminal vesicle secretion on it. Materials and Methods In this study, we evaluated FA composition of uterus phospholipids during the implantation period in intact and seminal vesicle-excised (SVX) mated female mice. Forty NMRI female mice were divided into control (mated with intact male) and seminal vesicle excised (SVX)-mated (mated with SVX-male) groups. The phospholipid fatty acids composition was monitored during the first five days of pregnancy using gas chromatography and also implantation rate was evaluated on fifth day of pregnancy. Results We found that levels of linoleic acid (LNA) and arachidonic acid (ARA) showed a decreasing trend from the first to the third day of pregnancy and then started to increase on the fourth day and peaked on the fifth day. In contrast, the level of saturated FA (SFA) increased on the second and third day of pregnancy compared to the first (p<0.05) and then decreased on the fourth and fifth. We also found that the seminal vesicle secretion could affect the levels of LNA, ARA, SFA, and PUFA in uterine phospholipids especially on second and third day. Moreover, there was a positive correlation between ARA level and implantation rate in control but not SVX-mated groups. Conclusions It can be concluded that several uterus FA that have important roles in early pregnancy could be affected by seminal vesicle secretion.


Assuntos
Animais , Masculino , Feminino , Implantação do Embrião/fisiologia , Glândulas Seminais/metabolismo , Útero/química , Modelos Animais , Ácidos Graxos/química , Tamanho do Órgão/fisiologia , Valores de Referência , Fatores de Tempo , Gravidez/metabolismo , Distribuição Aleatória , Ácidos Graxos/análise , Camundongos
14.
J Cell Physiol ; 234(11): 20240-20248, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-30950053

RESUMO

To evaluate the concentration of tumor necrosis factor α (TNF-α) and its soluble receptors (sTNFR I and II) in serum and follicular fluid (FF) at the time of oocyte retrieval and to detect expression of TNF-α and its receptors by luteinized granulosa cells (GCs). In a cross-sectional study and through an in vitro fertilization-intracytoplasmic sperm injection (IVF-ICSI) program, 81 women undergoing oocyte retrieval were recruited. Serum and FF were obtained from 81 women. GCs were pooled from 20 patients (from six different days of oocyte retrievals, 5-16 follicles per patient). TNF-α and its soluble receptors concentration were determined by enzyme-linked immunosorbent assay and also their expression by immune cytochemistry and reverse-transcription polymerase chain reaction analysis. The median TNF-α concentration in serum was 4.06 pg/ml (interquartile range [IQR], 3.71-6.14) and significantly higher than that in FF with 3.50 pg/ml (IQR, 3.05-5.01), p < 0.001. The sTNFR I and II levels in serum were lower and higher than FF, respectively. The TNF-α levels in serum and FF of good responders were higher than low responders (p = 0.017 and 0.021, respectively). TNF-α cut-off level for low responders versus good responders was 4.174 pg/ml in serum with a pregnancy rate of 25.8% and 40% for below and above of this level, respectively (p = 0.19). For FF, the cut-off value was 3.89 pg/ml. TNF-α and its receptors were expressed by GCs. The presence of TNF-α and its soluble receptors in serum and FF and their expression by GCs suggest an important role for this cytokine in ovarian function.


Assuntos
Líquido Folicular/metabolismo , Células da Granulosa/metabolismo , RNA Mensageiro/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Adulto , Estudos Transversais , Feminino , Fertilização in vitro/métodos , Humanos , Pessoa de Meia-Idade , Gravidez , Injeções de Esperma Intracitoplásmicas/métodos , Adulto Jovem
15.
Int Braz J Urol ; 45(4): 825-833, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30901177

RESUMO

PURPOSE: No comprehensive information is available about uterus fatty acid (FA) change during implantation period and possible effects of the seminal vesicle secretion on it. MATERIALS AND METHODS: In this study, we evaluated FA composition of uterus phospholipids during the implantation period in intact and seminal vesicle-excised (SVX) mated female mice. Forty NMRI female mice were divided into control (mated with intact male) and seminal vesicle excised (SVX)-mated (mated with SVX-male) groups. The phospholipid fatty acids composition was monitored during the fi rst fi ve days of pregnancy using gas chromatography and also implantation rate was evaluated on fi fth day of pregnancy. RESULTS: We found that levels of linoleic acid (LNA) and arachidonic acid (ARA) showed a decreasing trend from the fi rst to the third day of pregnancy and then started to increase on the fourth day and peaked on the fi fth day. In contrast, the level of saturated FA (SFA) increased on the second and third day of pregnancy compared to the fi rst (p<0.05) and then decreased on the fourth and fi fth. We also found that the seminal vesicle secretion could affect the levels of LNA, ARA, SFA, and PUFA in uterine phospholipids especially on second and third day. Moreover, there was a positive correlation between ARA level and implantation rate in control but not SVX-mated groups. CONCLUSIONS: It can be concluded that several uterus FA that have important roles in early pregnancy could be affected by seminal vesicle secretion.


Assuntos
Implantação do Embrião/fisiologia , Ácidos Graxos/química , Modelos Animais , Glândulas Seminais/metabolismo , Útero/química , Animais , Ácidos Graxos/análise , Feminino , Masculino , Camundongos , Tamanho do Órgão/fisiologia , Gravidez/metabolismo , Distribuição Aleatória , Valores de Referência , Fatores de Tempo
16.
Geburtshilfe Frauenheilkd ; 79(1): 86-93, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30686838

RESUMO

Introduction Adrenomedullin 2 (ADM2) and vascular endothelial growth factor (VEGF) affect ovarian function, especially angiogenesis and follicular development. The actions of VEGF can be antagonized by its soluble receptors, soluble Fms-like tyrosine kinase-1 (sFlt-1) and soluble VEGF receptor 2 (sVEGFR-2), as they decrease its free form. In the present study, we evaluated the relationship between follicular fluid (FF) levels of AMD2, VEGF and its soluble receptors, and ICSI outcomes. Materials and Methods ICSI cycle outcomes were evaluated and FF levels of VEGF, sFlt-1, sVEGFR-2 and ADM2 were determined using ELISA kits. Results FF levels of ADM2, VEGF, and sVEGFR-2 were significantly higher in non-responders compared to other ovarian response groups (p < 0.05). There were significant correlations between ADM2, VEGF and sVEGFR-2 levels as well as VEGF/sFlt-1 and VEGF/sVEGFR-2 ratios (r = 0.586, 0.482, 0.260, and - 0.366, respectively). Based on the ROC curve, the cutoff value for ADM2 as a non-responder predictor was 348.55 (pg/ml) with a sensitivity of 67.7% and a specificity of 94.6%. Conclusions For the first time we measured FF ADM2 levels to determine the relationship to VEGF and its soluble receptors. We suggest that ADM2 could be a potential predictive marker for non-responders. Although the exact function of ADM2 in ovarian angiogenesis is not yet understood, our study may shed light on the possible role of ADM2 in folliculogenesis and ovulation.

17.
Acta Neurol Taiwan ; 28(3): 66-74, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32002976

RESUMO

OBJECTIVE: Various numbers of factors such as oxidative stress, neurotoxins, and pesticides have been implicated in its pathophysiology of Parkinson's disease (PD). Paraoxonas1 (PON1) metabolizes xenobiotics, including pesticides. Therefore, we surveyed the relationship between PON1 polymorphisms with its activities in the pathogenesis of Parkinson's disease.. METHODS: We investigated polymorphisms of the PON1 (L55M and Q192R) by PCR-RFLP assays; we also measure the levels of PON1, TAC (total antioxidant capacity) and TOS (total oxidant status) with ELISA (Enzyme-linked immunosorbent assay) and spectrophotometric method for their activities. RESULTS: Paraoxonase and arylesterase activity of PON1 as well as their concentrations were lower in patients with PD compared with control group, but from the view of the specific activity, it was not significant between two groups. In the compare of TAC, TOS, and OSI, the TOS and OSI were higher in the patients than controls, while patients had lower levels of TAC compared with controls. Serum PON1 concentrations and activities were higher in LL (comparison with LM and MM) and RR (comparison with QR and QQ) genotypes while we did not observe any significant differences in arylesterase levels among mentioned polymorphisms. CONCLUSION: In the current study, we reported associations between PON1 polymorphisms (55, 192) and enzyme activities in Parkinson's disease as there was a significant reduction in PON1 levels in patients with Parkinson compared with healthy. Taken together, paraoxonase enzyme in subjects with different genotypes could be a potential biomarker for determining the severity and prognosis of Parkinson. However, more studies are needed to clarify its clinical values. Key words: Parkinson's disease; paraoxonase1; Polymorphism.


Assuntos
Arildialquilfosfatase/genética , Doença de Parkinson , Genótipo , Humanos , Doença de Parkinson/genética , Polimorfismo Genético
18.
EXCLI J ; 17: 945-951, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30564073

RESUMO

Microsatellite instability (MSI) is a unique molecular alteration that is due to a defective DNA mismatch repair (MMR) system. Approximately, 15-20 % of sporadic colorectal cancers (CRC) display MSI. Determination of MSI status in CRC has prognostic and predictive implications. Additionally, detecting MSI is used diagnostically for tumor detection and classification. The present study analyzed a panel of five mononucleotide markers, BAT-25, BAT-26, NR-21, NR-22 and NR-27, amplified in a single multiplex PCR reaction to evaluate MSI status in CRC patients. Genomic DNA from 50 CRC and paired adjacent normal tissues was used for PCR-based MSI analysis. Our finding showed microsatellite instability in 36 % of specimens. Instability with differences in allele lengths was observed in the tumoral DNA compared to the tumor-free margin DNA sample. The frequency of instability in NR-21, BAT-26 and BAT-25 markers were more than others; their frequency were 35.48 %, 29.03 %, and 22.58 %, respectively. In conclusion, the NR-21, BAT-26, and BAT-25 were the most useful markers for discriminating cancer tissue from normal, therefore these markers have demonstrated promising potential for determining MSI status in patients with sporadic colorectal cancer.

19.
Arch Toxicol ; 92(12): 3443-3457, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30155719

RESUMO

Sulfur mustard (SM) is an extensive nucleophilic and alkylating agent that targets different tissues. The genotoxic property of SM is the most threatening effect, because it is associated with detrimental inflammations and susceptibility to several kinds of cancer. Moreover, SM causes a wide variety of adverse effects on DNA which result in accumulation of DNA adducts, multiple mutations, aneuploidies, and epigenetic aberrations in the genome. However, these adverse effects are still not known well, possibly because no valid biomarkers have been developed for detecting them. The advent of next-generation sequencing (NGS) has provided opportunities for the characterization of these alterations with a higher level of molecular detail and cost-effectivity. The present review introduces NGS approaches for the detection of SM-induced DNA adducts, mutations, chromosomal structural variation, and epigenetic aberrations, and also comparing and contrasting them with regard to which might be most advantageous.


Assuntos
Substâncias para a Guerra Química/toxicidade , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Gás de Mostarda/toxicidade , Animais , Adutos de DNA/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Epigênese Genética/efeitos dos fármacos , Humanos , Testes de Mutagenicidade/métodos , Mutagênicos/toxicidade , Mutação/efeitos dos fármacos
20.
Biochem Biophys Res Commun ; 503(3): 1754-1760, 2018 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-30060953

RESUMO

Considering possible effects of poly-unsaturated fatty acids (PUFA) on embryo implantation more likely through PGs, we investigated effects of dietary omega-3 and -6 PUFA on prostaglandin E2 (PGE2) signaling in mice uterus during pre-implantation period. The mRNA expressions of microsomal- and cytosolic- PGE synthase (mPGES and cPGES) and protein expressions of PGE receptor 2 and 4 (EP2 and EP4) were evaluated in uterus tissues of control as well as omega 3 and omega 6 received mice at days 1-5 of pregnancy. Expression of cPGES gene was not significantly different between groups but the mPGES expression on days 4 and 5 of pregnancy in supplemented groups was higher than controls. Omega-3 significantly decreased EP2 levels on days 3 and 4, while omega-6 caused an increase on days 3-5 of pregnancy. The levels of EP4 were significantly higher in the omega-6 group than other groups on days 4 and 5 of pregnancy. Also the implantation rate was higher in omega -6 compared to omega-3 group (p = 0.006). Moreover, there were significant correlations between implantation rate with expression levels of mPGES and EP2. Our results showed negative and positive effects of respectively dietary omega-3 and -6 PUFA on PGE2 signaling and implantation rate.


Assuntos
Implantação do Embrião/efeitos dos fármacos , Ácidos Graxos Ômega-3/farmacologia , Ácidos Graxos Ômega-6/farmacologia , Prostaglandina-E Sintases/biossíntese , Receptores de Prostaglandina E Subtipo EP2/biossíntese , Útero/efeitos dos fármacos , Útero/metabolismo , Animais , Suplementos Nutricionais , Ácidos Graxos Ômega-3/administração & dosagem , Ácidos Graxos Ômega-6/administração & dosagem , Feminino , Masculino , Camundongos
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