Green synthesized silver nanoparticles have strong antioxidant and antibacterial activity due to the presence of bioactive molecules on the surface of silver nanoparticles.
Uterine serous papillary carcinoma (USPC) are high-grade tumors with Her2 gene expression and poor prognosis. The human gene Her2 is a proto-oncogene that encodes a protein with tyrosine kinase activity. The objective of this study was to determine Her2 protein expression and gene amplification in USPC using three methods: immunohistochemistry (IHC), chromogenic in situ hybridization (CISH), and quantitative polymerase chain reaction (Q-PCR), to compare the three techniques, and to correlate Her2 expression and amplification with clinical outcome. Clinical data were obtained from the records of the patients provided by the database of the Gynaecological Cancer Unit at the Royal Adelaide Hospital. Paraffin-embedded tissues of 45 cases were examined using three techniques. Her2 positive rate was 40%. About 13% was strongly positive by all three methods. About 67% Her2 positive patients had advanced-stage disease. Relapse rate was 61% (P = 0.6). Stages I and II had a better survival with negative receptor. Age and stage were major prognostic variables in Cox analysis. Marker status did not reach statistical significance in overall survival (OS) and relapse-free survival (RFS), but had a hazard ratio (HR) of 1.5 in RFS. Five-year OS with Her2 negative was 39%. HR was 0.97 (95% CI 0.46-2.1). RFS was 39% and HR was 1.4 (95% CI 0.65-2.9). The three methods have strong correlation. IHC, 3+ positive cases should be regarded as exhibiting evidence of gene amplification and do not require further testing. Equivocal results require further testing by CISH or PCR. Age and stage are strong prognostic variables and receptor status has a HR of 1.5 in RFS. The therapeutic role of Trastuzumab should be tested in clinical trial setting.
Autophagy is an important cellular self-digestion and recycling pathway that helps in maintaining cellular homeostasis. Dysregulation at various steps of the autophagic and endolysosomal pathway has been reported in several neurodegenerative disorders such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and Huntington disease (HD) and is cited as a critically important feature for central nervous system (CNS) proteostasis. Recently, another molecular target, namely transcription factor EB (TFEB) has been explored globally to treat neurodegenerative disorders. This TFEB, is a key regulator of autophagy and lysosomal biogenesis pathway. Multiple research studies suggested therapeutic potential by targeting TFEB to treat human diseases involving autophagy-lysosomal dysfunction, especially neurodegenerative disorders. A common observation involving all neurodegenerative disorders is their poor efficacy in clearing and recycle toxic aggregated proteins and damaged cellular organelles due to impairment in the autophagy pathway. This dysfunction in autophagy characterized by the accumulation of toxic protein aggregates leads to a progressive loss in structural integrity/functionality of neurons and may even result in neuronal death. In recent years TFEB, a key regulator of autophagy and lysosomal biogenesis, has received considerable attention. It has emerged as a potential therapeutic target in numerous neurodegenerative disorders like AD and PD. In various neurobiology studies involving animal models, TFEB has been found to ameliorate neurotoxicity and rescue neurodegeneration. Since TFEB is a master transcriptional regulator of autophagy and lysosomal biogenesis pathway and plays a crucial role in defining autophagy activation. Studies have been done to understand the mechanisms for TFEB dysfunction, which may yield insights into how TFEB might be targeted and used for the therapeutic strategy to develop a treatment process with extensive application to neurodegenerative disorders. In this review, we explore the role of different transcription factor-based targeted therapy by some natural compounds for AD and PD with special emphasis on TFEB.
Parkinson’s disease (PD) is one of the most debilitating brain diseases. Despite the availability of symptomatic treatments, response towards the health of PD patients remains scarce. To fulfil the medical needs of the PD patients, an efficacious and etiological treatment is required. In this review, we have compiled the information covering limitations of current therapeutic options in PD, novel drug targets for PD, and finally, the role of some critical beneficial natural products to control the progression of PD.
Background: Riboswitches are a type of noncoding RNA that regulate gene expression by switching from one structural conformation to another on ligand binding. The various classes of riboswitches discovered so far are differentiated by the ligand, which on binding induces a conformational switch. Every class of riboswitch is characterized by an aptamer domain, which provides the site for ligand binding, and an expression platform that undergoes conformational change on ligand binding. The sequence and structure of the aptamer domain is highly conserved in riboswitches belonging to the same class. We propose a method for fast and accurate identification of riboswitches using profile Hidden Markov Models (pHMM). Our method exploits the high degree of sequence conservation that characterizes the aptamer domain.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.