This study focuses on antibacterial, antioxidant and toxic potentials of Viscum album Linn, commonly known as European mistletoe associated with Acacia catechu (Khayer in Nepali). Methanol extract of the aerial parts of the Mistletoe was prepared by cold percolation method. The resulting extract was simultaneously subjected to phytochemical screening; anti-microbial activity; anti-oxidant potential and Brine shrimp toxicity test. The major biologically active phyto-constituents observed were alkaloids, glycosides, saponins, polyphenols, flavonoids, tannins, terpenoids and cardiac glycosides. Upon antibacterial activity screening, the plant extract was found to be highly effective against Pseudomonas aeruginosa with the zone of inhibition 16±1mm compared to 17±1mm of chloramphenicol (50 mcg). The antioxidant activity as EC50 value by DPPH (1,1-diphenyl-2-picrylhydrazyl) free radical scavenging activity was found to be 1.58 mg/ml while the ferric reducing capacity was measured to be 282.83±19.55 mg FeSO4.7H2O eqvt/g dry wt. of the extract during Ferric Ion Reducing Antioxidant Power (FRAP) Assay. The LC50 value for Brine Shrimp Toxicity Assay was found to be 31.62 ppm. This study shows the medicinal value of the mistletoe associated with Acacia catechu. Further meticulous analysis of this plant might lead to identification of active biomolecules effective as drugs for various ailments.

The interplay between glycolysis and mitochondrial oxidative phosphorylation (OXPHOS) is central to maintain energy homeostasis. It remains to be determined whether there is a mechanism governing metabolic fluxes based on substrate availability in microenvironments. Here we show that menin is a key transcription factor regulating the expression of OXPHOS and glycolytic genes in cancer cells and primary tumors with poor prognosis. A group of menin-associated proteins (MAPs), including KMT2A, MED12, WAPL, and GATA3, is found to restrain menin’s full function in this transcription regulation. shRNA knockdowns of menin and MAPs result in reduced ATP production with proportional alterations of cellular energy generated through glycolysis and OXPHOS. When shRNA knockdown cells are exposed to metabolic stress, the dual functionality can clearly be distinguished among these metabolic regulators. A MAP can negatively counteract the regulatory mode of menin for OXPHOS while the same protein positively influences glycolysis. A close-proximity interaction between menin and MAPs allows transcriptional regulation for metabolic adjustment. This coordinate regulation by menin and MAPs is necessary for cells to rapidly adapt to fluctuating microenvironments and to maintain essential metabolic functions.

Background: Chromothripsis is an event of genomic instability leading to complex chromosomal alterations in cancer. Frequent long-range chromatin interactions between transcription factors (TFs) and targets may promote extensive translocations and copy-number alterations in proximal contact regions through inappropriate DNA stitching. Although studies have proposed models to explain the initiation of chromothripsis, few discussed how TFs influence this process for tumor progression. Methods: This study focused on genomic alterations in amplification associated regions within chromosome 17. Inter−/intra-chromosomal rearrangements were analyzed using whole genome sequencing data of breast tumors in the Cancer Genome Atlas (TCGA) cohort. Common ERα binding sites were defined based on MCF-7, T47D, and MDA-MB-134 breast cancer cell lines using univariate K-means clustering methods. Nanopore sequencing technology was applied to validate frequent rearrangements detected between ATC loci on 17q23 and an ERα hub on 20q13. The efficacy of pharmacological inhibition of a potentially druggable target gene on 17q23 was evaluated using breast cancer cell lines and patient-derived circulating breast tumor cells.

Highlights d Inhibition of aKG-dependent demethylation destabilizes chromatin regulatory landscape d 2HG subverts lineage fidelity and increases cell-level variability in motif accessibility d 2HG-high breast tumors display enhanced cellular heterogeneity d A2P eradicates heterogeneity in high 2HG-producing basallike cancer cells

Among single-cell analysis technologies, single-cell RNA-seq (scRNA-seq) has been one of the front runners in technical inventions. Since its induction, scRNA-seq has been well received and undergone many fast-paced technical improvements in cDNA synthesis and amplification, processing and alignment of next generation sequencing reads, differentially expressed gene calling, cell clustering, subpopulation identification, and developmental trajectory prediction. scRNA-seq has been exponentially applied to study global transcriptional profiles in all cell types in humans and animal models, healthy or with diseases, including cancer. Accumulative novel subtypes and rare subpopulations have been discovered as potential underlying mechanisms of stochasticity, differentiation, proliferation, tumorigenesis, and aging. scRNA-seq has gradually revealed the uncharted territory of cellular heterogeneity in transcriptomes and developed novel therapeutic approaches for biomedical applications. This review of the advancement of scRNA-seq methods provides an exploratory guide of the quickly evolving technical landscape and insights of focused features and strengths in each prominent area of progress.