<b><i>Background:</i></b> Gastric cancer (GC) is recorded as the fifth most common cancer globally. The classic resemblance of early symptoms of chronic gastritis including nausea, dysphagia, and dyspepsia with GC is the current challenge limiting the early diagnosis of GC. The current diagnostic procedures of GC are limited due to their invasive nature. This directs the research question toward alternative approaches, specifically at the molecular level. Recent advances in molecular regulation of cancer suggest the prominence of circular RNAs (circRNAs) in the multistep process of tumourigenesis. <b><i>Summary:</i></b> CircRNAs are a class of non-coding RNAs, abundant in eukaryotes, with key roles in regulating genes and miRNAs as well as the alteration of processes involved in pathological conditions. Research studies have demonstrated the participation of circRNAs in the initiation and progression of tumours. This review provides a comprehensive insight into the potential of circRNAs as disease biomarkers for the early detection and treatment of GC. <b><i>Key Messages:</i></b> This study is an amalgamation of the implications and future prospects of circRNAs for the detection and potential treatment of GC.
Background Parkinson’s disease (PD) is a multifactorial neurodegenerative disorder marked by the death of nigrostriatal dopaminergic neurons in response to the compounding effects of oxidative stress, mitochondrial dysfunction and protein aggregation. Transgenic Drosophila models have been used extensively to decipher the underlying genetic interactions that exacerbate neural health in PD. Autosomal recessive forms of the disease have been linked to mutations in the serine/threonine kinase PINK1(PTEN-Induced Putative Kinase 1) and E3 ligase Parkin, which function in an axis that is conserved in flies. This review aims to probe the current understanding of PD pathogenesis via the PINK1/Parkin axis while underscoring the importance of several molecular and pharmacologic rescues brought to light through studies in Drosophila. Main body Mutations in PINK1 and Parkin have been shown to affect the axonal transport of mitochondria within dopaminergic neurons and perturb the balance between mitochondrial fusion/fission resulting in abnormal mitochondrial morphology. As per studies in flies, ectopic expression of Fwd kinase and Atg-1 to promote fission and mitophagy while suppressing fusion via MUL1 E3 ligase may aid to halt mitochondrial aggregation and prolong the survival of dopaminergic neurons. Furthermore, upregulation of Hsp70/Hsp90 chaperone systems (Trap1, CHIP) to target misfolded mitochondrial respiratory complexes may help to preserve their bioenergetic capacity. Accumulation of reactive oxygen species as a consequence of respiratory complex dysfunction or antioxidant enzyme deficiency further escalates neural death by inducing apoptosis, lipid peroxidation and DNA damage. Fly studies have reported the induction of canonical Wnt signalling to enhance the activity of transcriptional co-activators (PGC1α, FOXO) which induce the expression of antioxidant enzymes. Enhancing the clearance of free radicals via uncoupling proteins (UCP4) has also been reported to ameliorate oxidative stress-induced cell death in PINK1/Parkin mutants. Conclusion While these novel mechanisms require validation through mammalian studies, they offer several explanations for the factors propagating dopaminergic death as well as promising insights into the therapeutic importance of transgenic fly models in PD.
Nano scale materials possess unique properties that are generally not seen in their bulk counterparts. Though chemical and physical methods of nano particle synthesis is widely used, the advantage of biological synthesis have gained popularity owing to their environment affability. Green synthesis of nanoparticles has gained importance in biomedical research owing to its ease of synthesis, better stability of the nanoparticles and cost effectiveness. Cadmium sulphide nanoparticles (CdS) have been extensively studied to have potential applications in the field of biomedical research and imaging studies.In the present study, CdS nanoparticles were synthesized using Bacillus licheniformis as the precursor. The thus synthesized CdS nanoparticles were characterized by scanning electron microscopy and the nano dimension of the particle was confirmed. Four different concentrations of CdS nanoparticles were tested to assess its genotoxicity using Drosophila melanogaster as the in-vivo model. Additionally, the antimicrobial property of CdS was also examined by well diffusion and macro dilution method. The results suggested significant antimicrobial activity and lack of genotoxicity of CdS nanoparticles.
The antibacterial activity of β-lactam derived polycyclic fused pyrrolidine/pyrrolizidine derivatives synthesized by 1, 3-dipolar cycloaddition reaction was evaluated against microbes involved in dental infection. Fifteen compounds were screened; among them compound 3 showed efficient antibacterial activity in an ex vivo dentinal tubule model and in vivo mice infectious model. In silico docking studies showed greater affinity to penicillin binding protein. Cell damage was observed under Scanning Electron Microscopy (SEM) which was further proved by Confocal Laser Scanning Microscope (CLSM) and quantified using Flow Cytometry by PI up-take. Compound 3 treated E. faecalis showed ROS generation and loss of membrane integrity was quantified by flow cytometry. Compound 3 was also found to be active against resistant E. faecalis strains isolated from failed root canal treatment cases. Further, compound 3 was found to be hemocompatible, not cytotoxic to normal mammalian NIH 3T3 cells and non mutagenic. It was concluded that β-lactam compound 3 exhibited promising antibacterial activity against E. faecalis involved in root canal infections and the mechanism of action was deciphered. The results of this research can be further implicated in the development of potent antibacterial medicaments with applications in dentistry.
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