ABSTRACT
Meniere's disease (MD) is a severe inner ear condition known by debilitating symptoms, including spontaneous vertigo, fluctuating and progressive hearing loss, tinnitus, and aural fullness or pressure within the affected ear. Prosper Meniere first described the origins of MD in the 1860s, but its underlying mechanisms remain largely elusive today. Nevertheless, researchers have identified a key histopathological feature called Endolymphatic Hydrops (ELH), which refers to the excessive buildup of endolymph fluid in the membranous labyrinth of the inner ear. The exact root of ELH is not fully understood. Still, it is believed to involve several biological and bioenvironmental etiological factors such as genetics, autoimmunity, infection, trauma, allergy, and new theories, such as saccular otoconia blocking the endolymphatic duct and sac. Regarding treatment, there are no reliable and definitive cures for MD. Most therapies focus on managing symptoms and improving the overall quality of patients' life. To make significant advancements in addressing MD, it is crucial to gain a fundamental understanding of the disease process, laying the groundwork for more effective therapeutic approaches. This paper provides a comprehensive review of the pathophysiology of MD with a focus on old and recent theories. Current treatment strategies and future translational approaches (with low-level evidence but promising results) related to MD are also discussed, including patents, drug delivery, and nanotechnology, that may provide future benefits to patients suffering from MD.
Subject(s)
Endolymphatic Hydrops , Meniere Disease , Humans , Meniere Disease/diagnosis , Meniere Disease/therapy , Endolymphatic Hydrops/diagnosis , Endolymphatic Hydrops/etiology , Otolithic MembraneABSTRACT
Uterine leiomyoma (UL), as the most prevalent type of women's health disorders, is a benign tumor that originates from the smooth muscle cell layer of the uterus. A great number of associated complications are observed including infertility, miscarriage, bleeding, pain, dysmenorrhea, menorrhagia, and dyspareunia. Although the etiology of UL is largely undefined, environmental and genetic factors are witnessed to engage in the UL development. As long non-coding RNAs (lncRNAs) are involved in various types of cellular functions, in recent years, a great deal of attention has been drawn to them and their possible roles in UL pathogenesis. Moreover, they have illustrated their potential to be promising candidates for UL treatment. In this review paper, firstly, an overview of UL pathogenesis is presented. Then, the regulation of lncRNAs in UL and their possible mechanisms in cancer development are reviewed. Eventually, therapeutic approaches targeting lncRNAs in various cancers and UL are explored.
Subject(s)
Leiomyoma , RNA, Long Noncoding , Uterine Neoplasms , Female , Humans , Leiomyoma/metabolism , Leiomyoma/pathology , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Uterine Neoplasms/genetics , Uterine Neoplasms/metabolism , Uterine Neoplasms/pathologyABSTRACT
INTRODUCTION: Uterine leiomyoma (ULM) is the most common gynecological tumor. Recent studies have revealed the role of hypovitaminosis D as a major risk factor in the disease development. CYP24A, a mitochondrial enzyme that catalyzes the degradation of 1,25(OH)2D3, is reported to be over-expressed in several human cancers. In this study, we aimed to investigate the expression level of CYP24A1 in leiomyoma samples compared with the adjacent tissues regarding the MED12 mutation profile. MATERIALS AND METHODS: In the present study, 61 ULMs and adjacent tissue samples were collected from 51 women undergoing hysterectomy and myomectomy. The samples were Sanger sequenced for MED12 mutation, and the expression level of CYP24A1 was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: The results demonstrated that CYP24A1 gene was ectopically expressed in 18% of uterine leiomyoma tissues, although this expression was independent of the MED12 mutation profile. CONCLUSION: The findings of the present study support current evidence that dysregulation of vitamin D signaling and metabolic pathways may be involved in at least some subtypes of ULMs.
Subject(s)
Leiomyoma/genetics , Mediator Complex/genetics , Uterine Neoplasms/genetics , Vitamin D3 24-Hydroxylase/genetics , Adult , Ectopic Gene Expression , Female , Gene Expression Regulation, Neoplastic , Humans , Hysterectomy , Leiomyoma/pathology , Mediator Complex/metabolism , Middle Aged , Mutation/genetics , Reverse Transcriptase Polymerase Chain Reaction , Uterine Myomectomy , Uterine Neoplasms/pathology , Vitamin D3 24-Hydroxylase/metabolismABSTRACT
HIV-1 transactivator of transcription protein is one of the most promising AIDS vaccine candidates and plays central roles in the virus life cycle and pathogenesis. Understanding structural properties of vaccine candidate antigens leads to rational design of vaccines which improves their presentation to immune system and facilitates their manufacturing and storage. This study aims to investigate structural properties and stability of one variant of HIV-1 Tat recombinant protein using different spectroscopic, electrophoretic, and microscopic methods. Therefore, after the gene transformation, protein expression was optimized in E. coli cells and the C-terminal His6-tagged protein was purified using Ni-NTA resin. The structural stability of the pure protein was then investigated under different conditions including pH, Zn2+ ions, thermal and chemical stress. Acidic and alkaline pHs affects spectroscopic properties of the vaccine in different ways. The structure unfolding experiment shows relatively poor stability of the zinc-free protein sample compared to the ion-containing one. According to the quenching experiment and also thermal stability study results, the protein has attained more structural compactness in the presence of Zn2+. Secondary structure of the protein is mainly disordered and didn't significantly affect under various conditions. Finally, different degrees of oligomerization and aggregation were found under physiological conditions.