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PURPOSE: Steroid hormone secretion is one of the key functions of granulosa cells (GCs). Resveratrol is a natural polyphenol, known for its beneficial health effects, such as improving reproductive health. However, its application is limited due to poor bioavailability. The methoxy derivative of resveratrol (DMU-212) was demonstrated to be more lipophilic, and therefore of greater bioavailability. However, since the addition of methoxy groups to the stilbene scaffold was found to make the molecule insoluble in water, DMU-212 was loaded into liposomes. This study aimed to evaluate how the liposomal formulation of DMU-212 (lipDMU-212) alters estradiol and progesterone secretion of human ovarian GCs in a primary three-dimensional cell culture model. METHODS: DMU-212-loaded liposomes were prepared by thin film hydration followed by extrusion. Cell viability was measured after exposure of GCs spheroids to the liposomal formulation of DMU-212 using CellTiter-Glo® 3D Cell Viability Assay. The secretion of estradiol and progesterone was determined using commercial ELISA kits. RT-qPCR was conducted to analyze the expression of steroidogenesis-related genes. Finally, the western blot technique was used to analyze the effect of lipDMU-212 and FSH treatments on CYP11A1 and HSD3B1 protein levels. RESULTS: lipDMU-212 was found to significantly increase estradiol and progesterone secretion in a dose-dependent manner by enhancing the expression of CYP11A1, HSD3B1, StAR, CYP17A1, CYP19A1, and HSD17B1 genes. We have also shown that lipDMU-212, used alone and in combination with FSH, significantly increased the expression of the HSD3B1 and CYP11A1 proteins in GCs. Furthermore, our study suggests that lipDMU-212 increases FSH activity. CONCLUSIONS: This is the first study to describe the steroidogenic activity of liposomal formulation of DMU-212, possibly through increasing the StAR and CYP19A1 expression. These findings suggest that lipDMU-212 might have a beneficial effect in the treatment of disorders related to estrogen deficiency and hyperandrogenism, such as PCOS.
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Progesterona , Estilbenos , Feminino , Humanos , Resveratrol/farmacologia , Resveratrol/metabolismo , Progesterona/farmacologia , Enzima de Clivagem da Cadeia Lateral do Colesterol/metabolismo , Lipossomos/metabolismo , Lipossomos/farmacologia , Estilbenos/farmacologia , Estilbenos/metabolismo , Estradiol/farmacologia , Hormônio Foliculoestimulante/metabolismo , Células da Granulosa/metabolismo , Complexos Multienzimáticos/metabolismo , Complexos Multienzimáticos/farmacologiaRESUMO
Purpose: Subependymoma is a slow-growing benign brain neoplasm, classified by the World Health Organization (WHO) as a grade I tumor, which typically presents in middle-aged male adults. Case description: A case of Bruns syndrome and an intraventricular subependymoma in a 49-year-old patient who presented with intractable headache and vertigo is discussed in this paper. Imaging revealed a well-delimited cystic and solid mass near the lateral ventricle. Comment: Complete surgical excision of the tumor resulted in the restoration of normal cerebrospinal fluid pathway and resolution of clinical symptoms with no signs of tumor recurrence in the 4-year follow-up period.
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Neurological diseases can be broadly divided according to causal factors into circulatory system disorders leading to ischemic stroke; degeneration of the nerve cells leading to neurodegenerative diseases, such as Alzheimer's (AD) and Parkinson's (PD) diseases, and immune system disorders; bioelectric activity (epileptic) problems; and genetically determined conditions as well as viral and bacterial infections developing inflammation. Regardless of the cause of neurological diseases, they are usually accompanied by disturbances of the central energy in a completely unexplained mechanism. The brain makes up only 2% of the human body's weight; however, while working, it uses as much as 20% of the energy obtained by the body. The energy requirements of the brain are very high, and regulatory mechanisms in the brain operate to ensure adequate neuronal activity. Therefore, an understanding of neuroenergetics is rapidly evolving from a "neurocentric" view to a more integrated picture involving cooperativity between structural and molecular factors in the central nervous system. This article reviewed selected molecular biomarkers of oxidative stress and energy metabolism disorders such as homocysteine, DNA damage such as 8-oxo2dG, genetic variants, and antioxidants such as glutathione in selected neurological diseases including ischemic stroke, AD, PD, and epilepsy. This review summarizes our and others' recent research on oxidative stress in neurological disorders. In the future, the diagnosis and treatment of neurological diseases may be substantially improved by identifying specific early markers of metabolic and energy disorders.
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AVC Isquêmico , Doenças Metabólicas , Doenças Neurodegenerativas , Humanos , Estresse Oxidativo/fisiologia , Antioxidantes/metabolismo , Doenças Neurodegenerativas/metabolismo , Metabolismo Energético/fisiologia , AVC Isquêmico/complicaçõesRESUMO
Polycystic ovary syndrome (PCOS) is the most common heterogeneous endocrine disorder among women of reproductive age. The pathogenesis of PCOS remains elusive; however, there is evidence suggesting the potential contribution of genetic interactions or predispositions combined with environmental factors. Among these, endocrine disrupting chemicals (EDCs) have been proposed to potentially contribute to the etiology of PCOS. Granulosa and theca cells are known to cooperate to maintain ovarian function, and any disturbance can lead to endocrine disorders, such as PCOS. This article provides a review of the recent knowledge on PCOS pathophysiology, the role of granulosa and theca cells in PCOS pathogenesis, and the evidence linking exposure to EDCs with reproductive disorders such as PCOS.
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Disruptores Endócrinos , Síndrome do Ovário Policístico , Feminino , Humanos , Disruptores Endócrinos/toxicidade , Células da Granulosa/patologiaRESUMO
Cerebral amyloid angiopathy (CAA) is a chronic pathological condition characterized by progressive accumulation of amyloid protein in the wall of cerebral blood vessels, both leptomeningeal and cortical. That may result in the development of such conditions as microaneurysms, hemorrhagic, ischaemic brain injury and contribute to cognitive impairment. We herein report a case of Iowa-type hereditary cerebral amyloid angiopathy (CAA) mutation diagnosed with MS. The family of the reported patient had performed genetic testing due to the history of intracerebral hemorrhage. Sequence analysis of exon 17 of the APP gene showed the presence of the D694N g.275272 G > A (c.2080 G > A) mutation, which caused the substitution of aspartate for aspargine at position 694 of APP. Alike the discussed patient, this mutation has been found in other family members in an autosomal dominant pattern of inheritance. Contrary to the rest of the family, the reported patient has been diagnosed with multiple sclerosis based on McDonald criteria. Recent studies shed light on the possible link between the APP accumulation and MS progression. It has been indicated that amyloid can prove a vital role in neuroimmunology, whereas the accumulation of APP in the CNS has been suggested to be a potential biomarker for the progression of MS. Moreover, the amyloid positron-emission tomography (amyloid-PET) has been demonstrated to serve as a diagnostic tool for establishing the degree of demyelination and remyelination in MS. Even though, one swallow does not make a summer, this finding would be another step forward in the understanding of pathological processes underlying the pathogenesis of MS.
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Angiopatia Amiloide Cerebral , Esclerose Múltipla , Biomarcadores , Angiopatia Amiloide Cerebral/complicações , Angiopatia Amiloide Cerebral/diagnóstico por imagem , Angiopatia Amiloide Cerebral/genética , Humanos , Esclerose Múltipla/complicações , Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla/genética , Mutação , Tomografia por Emissão de PósitronsRESUMO
Lung cancer is one of the most common causes of cancer death. Its poor prognosis can be attributed to the patients' advanced or metastatic presentation at the time of diagnosis. To improve and accelerate the diagnosis, better therapeutic and diagnostic methods are constantly being sought. MicroRNAs (miRNAs) are short nucleotide sequences of single-stranded, non-coding RNA that function as critical post-transcriptional regulators of gene expression. They are identified not only intracellularly, but also in physiological and pathological body fluids. These molecules are responsible for the regulation of approximately 33% of human genes, either regulating the expression of both oncogenes and suppressor genes or acting directly as an oncogene or suppressor gene itself. MiRNAs can contribute to the formation of cancer. The high specificity and sensitivity of miRNAs have been demonstrated with various malignant diseases, and for this reason, they raise particular interest as new and perspective biomarkers of tumours. Our work summarises the available information from recent years regarding the possibility of using miRNAs as biomarkers in the diagnosis of neoplasms. In this review, we focused on malignant pleural effusions with an emphasis on non-small cell lung cancer (NSCLC).
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Extensive research in recent decades has expanded our insights into the pathogenesis of Parkinson's disease (PD), though the underlying cause remains incompletely understood. Neuroinflammation have become a point of interest in the interconnecting areas of neurodegeneration and infectious diseases. The hypothesis concerning an infectious origin in PD stems from the observation of Parkinson-like symptoms in individuals infected with the influenza virus who then developed encephalitis lethargica. The implications of infectious pathogens have later been studied in neuronal pathways leading to the development of Parkinsonism and PD, through both a direct association and through synergistic effects of infectious pathogens in inducing neuroinflammation. This review explores the relationship between important infectious pathogens and Parkinsonism, including symptoms of Parkinsonism following infectious etiologies, infectious contributions to neuroinflammation and neurodegenerative processes associated with Parkinsonism, and the epidemiologic correlations between infectious pathogens and idiopathic PD.
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Negative-pressure wound therapy (NPWT) is used to treat many different types of wounds, but there is still a lack of large studies describing its effectiveness in breast surgery. Enhanced recovery, reduction of complications, and good scar quality might be improved by the application of NPWT. Existing data show that vacuumassisted closure (VAC) application after expander-based breast reconstruction may be beneficial because of decreasing overall complications in comparison with standard wound treatment. There are few cases in which the use of negative pressure resulted in healing of complicated breast wounds after implant insertion - most breasts achieved healing, wherein duration of NPWT ranged from seven to 21 days. The use of NPWT leads to a decrease of seroma formation (from 70% to 15%), the mean percutaneous aspirated volume (from 193 ml to 26 ml) and the numbers of percutaneous aspirations (from three to one) in latissimus dorsi flap reconstruction. Furthermore, a prospective, within-patient, randomised study with 200 participants showed that treating closed incisional wounds after reduction mammoplasty with a VAC system resulted in a decrease of overall complications and protected against wound dehiscence. In the literature, there are cases showing that NPWT may be useful for the successful treatment of chronic and non-healing wounds, included non-puerperal mastitis and surgical sites affected by radiation therapy due to breast cancer. There is still a need for evidence confirming the effectiveness of NPWT in breast surgery because of the deficiency of large prospective studies that compare NPWT with standard treatment.
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Epilepsy is a group of chronic neurological disorders characterized by recurrent, spontaneous, and unpredictable seizures. It is one of the most common neurological disorders, affecting tens of millions of people worldwide. Comprehensive studies on epilepsy in recent decades have revealed the complexity of epileptogenesis, in which immunological processes, epigenetic modifications, and structural changes in neuronal tissues have been identified as playing a crucial role. This review discusses the recent advances in the biomarkers of epilepsy. We evaluate the possible molecular background underlying the clinical changes observed in recent studies, focusing on therapeutic investigations, and the evidence of their safety and efficacy in the human population. This article reviews the pathophysiology of epilepsy, including recent reports on the effects of oxidative stress and hypoxia, and focuses on specific biomarkers and their clinical implications, along with further perspectives in epilepsy research.