Reprogramming of Cellular Plasticity via ETS and MYC Core-regulatory Circuits During Response to MAPK Inhibition in BRAF-mutant Colorectal Cancer.

Background: Aberrant enhancer dynamics play a critical role in the initiation and progression of colorectal cancer (CRC). BRAF -mutated metastatic CRC may be a unique subtype, exhibiting a strong epigenetic phenotype. Interestingly, bromodomain 2, a reader protein for H3K27ac-marked enhancers, was found to be synthetically lethal in CRC with BRAF + EGFR inhibition.

Targeted activation of Nrf2 at sites of oxidative stress reverses doxorubicin-induced cognitive impairments in mice.

While cancer survivorship has increased due to advances in treatments, chemotherapy often carries long-lived neurotoxic side effects which reduce quality of life. Commonly affected domains include memory, executive function, attention, and processing speed, known as chemotherapy-induced cognitive impairment or "chemobrain". Oxidative stress and neuroimmune signaling in the brain have been mechanistically linked to the deleterious effects of chemotherapy on cognition.

Single-Nucleus RNA Sequencing of HDAC6 Inhibition in Resolving Doxorubicin-Induced Cognitive Impairment.

Breast cancer is the most common cancer worldwide, accounting for 12.5% of all new cases. Doxorubicin, an effective treatment for breast cancer, is associated with chemotherapy-induced cognitive impairment (CICI), which affects up to 82% of survivors.

Alteration in oxidative/nitrosative disparity and nephroprotective effect of hydroethanolic extract of L. in gentamicin-induced acute kidney injury.

Background: Antibacterial, antioxidant, and antilipidemic properties of are well known from previous studies. This study was designed to study the phytochemical constituents, antioxidant efficacy, nephroprotective activity, and immunomodulatory potential of hydroethanolic extract in gentamicin-induced acute kidney injury (AKI) rat model.

Methods: extract was given for 8 days to gentamicin-induced toxicity (100 mg/kg) in rats.

Single-Phase Solid-Solution Reaction Facilitated Sodium-Ion Storage in Indium-Substituted Monoclinic Sodium-Iron Phosphomolybdate Cathodes.

Despite being a compelling alternative to the existing lithium-ion battery technology, the unavailability of cathodes with high energy density and capacity poses a key challenge toward the wider adaption of sodium-ion batteries (NIB). In this regard, iron-rich NASICONs have triggered significant attention owing to a greater abundance of Fe and higher operating voltages of Fe/Fe redox-couple. A major roadblock in such cathodes stems from the voltage hysteresis at higher current rates.

Characterization of a novel virulent mycobacteriophage Kashi-SSH1 (KSSH1) depicting genus-specific broad-spectrum anti-mycobacterial activity.

Aim: Tuberculosis (TB) is one of the leading infectious disease causing mortality in the world and the rise of drug resistance; multi-drug resistance (MDR) and extensive-drug resistance (XDR) has added to extra complicacy of the disease. In this scenario, phage therapy has emerged as a potential treatment option against drug-sensitive/-resistant strains.

Materials And Methods: The mycobacteriophage Kashi-SSH1 (KSSH1) was isolated from soil sample and was genomically, phenotypically, and functionally characterized.

Restricted Cortical Activity Involving Parietal Lobe and Sublobar Region Leads to Generalized Spike-Wave Discharges of Juvenile Myoclonic Epilepsy: Evidence from an EEG Source Localization Study.

Background: Previous studies have localized the origin of "generalized" spike-wave discharges of idiopathic generalized epilepsies to specific brain regions. Although there are studies in juvenile myoclonic epilepsy (JME) which have investigated the origin of spike-wave discharges, reports on the propagation of discharges are sparse.

Objective: The current study investigated the propagation of spike-wave discharges in JME, which was investigated by statistically comparing the electroencephalography (EEG)-derived cortical source activity during (a) various phases of spike-wave discharge versus background (eyes closed) activity, and (b) various phases of the first spike wave versus the corresponding phase of subsequent spike waves.

Epigenome Reprogramming Through H3K27 and H3K4 Trimethylation as a Resistance Mechanism to DNA Methylation Inhibition in BRAFV600E-Mutated Colorectal Cancer.

Purpose: BRAFV600E-mutated colorectal cancer exhibits a strong correlation with DNA hypermethylation, suggesting that this subgroup of tumors presents unique epigenomic phenotypes. Nonetheless, 5-azacitidine, which inhibits DNA methyltransferase activity, is not efficacious in BRAFV600E colorectal cancer in vivo.

Experimental Design: We randomized and treated mice implanted with patient-derived tumor xenografts harboring BRAFV600E mutation with control, 5-azacitidine, vemurafenib (BRAF inhibitor), or the combination.

Systemic and targeted activation of Nrf2 reverses doxorubicin-induced cognitive impairments and sensorimotor deficits in mice.

While cancer survivorship has increased due to advances in treatments, chemotherapy often carries long-lived neurotoxic side effects which reduce quality of life. Commonly affected domains include memory, executive function, attention, processing speed and sensorimotor function, colloquially known as chemotherapy-induced cognitive impairment (CICI) or "chemobrain". Oxidative stress and neuroimmune signaling in the brain have been mechanistically linked to the deleterious effects of chemotherapy on cognition and sensorimotor function.

Rules and impacts of nonsense-mediated mRNA decay in the degradation of long noncoding RNAs.

Nonsense-mediated mRNA decay (NMD) is a quality-control process that selectively degrades mRNAs having premature termination codon, upstream open reading frame, or unusually long 3'UTR. NMD detects such mRNAs and rapidly degrades them during initial rounds of translation in the eukaryotic cells. Since NMD is a translation-dependent cytoplasmic mRNA surveillance process, the noncoding RNAs were initially believed to be NMD-resistant.

A Dual Therapeutic Approach to Diabetes Mellitus via Bioactive Phytochemicals Found in a Poly Herbal Extract by Restoration of Favorable Gut Flora and Related Short-Chain Fatty Acids.

Diabetes mellitus (DM), a metabolic and endocrine condition, poses a serious threat to human health and longevity. The emerging role of gut microbiome associated with bioactive compounds has recently created a new hope for DM treatment. UHPLC-HRMS methods were used to identify these compounds in a poly herbal ethanolic extract (PHE).

Tsyn-Seq: a T-cell Synapse-Based Antigen Identification Platform.

Tools for genome-wide rapid identification of peptide-major histocompatibility complex targets of T-cell receptors (TCR) are not yet universally available. We present a new antigen screening method, the T-synapse (Tsyn) reporter system, which includes antigen-presenting cells (APC) with a Fas-inducible NF-κB reporter and T cells with a nuclear factor of activated T cells (NFAT) reporter. To functionally screen for target antigens from a cDNA library, productively interacting T cell-APC aggregates were detected by dual-reporter activity and enriched by flow sorting followed by antigen identification quantified by deep sequencing (Tsyn-seq).

Contrast Induced Sialadenitis with Low Volume Non-ionic Contrast in a Patient with Cerebral Venous Sinus Thrombosis.

Unlabelled: Background: Contrast Induced Sialadenitis or Iodide Mumps refers to non-suppurative inflammation of salivary glands following intravenous iodinated contrast administration. It is a rare adverse effect of iodinated contrast with only a few cases reported worldwide. It is hypothesized to be an idiosyncratic reaction due to toxic accumulation of iodine in salivary glands.

Isolation and characterization of a novel mycobacteriophage Kashi-VT1 infecting species.

Mycobacteriophages are viruses that infect members of genus . Because of the rise in antibiotic resistance in mycobacterial diseases such as tuberculosis, mycobacteriophages have received renewed attention as alternative therapeutic agents. Mycobacteriophages are highly diverse, and, on the basis of their genome sequences, they are grouped into 30 clusters and 10 singletons.

CRISPR/Cas genome editing in tomato improvement: Advances and applications.

The narrow genetic base of tomato poses serious challenges in breeding. Hence, with the advent of clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein9 (CRISPR/Cas9) genome editing, fast and efficient breeding has become possible in tomato breeding. Many traits have been edited and functionally characterized using CRISPR/Cas9 in tomato such as plant architecture and flower characters (e.

Epigenetic Perspective of Immunotherapy for Cancers.

Immunotherapy has brought new hope for cancer patients in recent times. However, despite the promising success of immunotherapy, there is still a need to address major challenges including heterogeneity in response among patients, the reoccurrence of the disease, and iRAEs (immune-related adverse effects). The first critical step towards solving these issues is understanding the epigenomic events that play a significant role in the regulation of specific biomolecules in the context of the immune population present in the tumor immune microenvironment (TIME) during various treatments and responses.

Phytochemicals, Antioxidant, Anti-inflammatory Studies, and Identification of Bioactive Compounds Using GC-MS of Ethanolic Novel Polyherbal Extract.

Hyperglycemia is the hallmark of diabetes, which is a collection of related metabolic disorders. Over time, diabetes can cause a variety of problems, including cardiovascular disease, nephropathy, neuropathy, and retinopathy. Ethanolic novel polyherbal extract (PHE) was prepared by mixing equal amounts of the following ingredients: Terminalia chebula Retz.

Dysregulation and Epigenetic Reprogramming of NRF2 Signaling Axis Promote Acquisition of Cisplatin Resistance and Metastasis in Head and Neck Squamous Cell Carcinoma.

Purpose: Cisplatin (CDDP)-based chemotherapy is a first-line treatment for patients with advanced head and neck squamous cell carcinomas (HNSCC), despite a high rate of treatment failures, acquired resistance, and subsequent aggressive behavior. The purpose of this study was to study the mechanism of CDDP resistance and metastasis in HNSCC. We investigated the role of NRF2 pathway activation as a driven event for tumor progression and metastasis of HNSCC.

Hsrω and Other lncRNAs in Neuronal Functions and Disorders in .

Long noncoding RNAs (lncRNAs) have a crucial role in epigenetic, transcriptional and posttranscriptional regulation of gene expression. Many of these regulatory lncRNAs, such as MALAT1, NEAT1, HOTAIR, etc., are associated with different neurodegenerative diseases in humans.

Complex I inhibitor of oxidative phosphorylation in advanced solid tumors and acute myeloid leukemia: phase I trials.

Although targeting oxidative phosphorylation (OXPHOS) is a rational anticancer strategy, clinical benefit with OXPHOS inhibitors has yet to be achieved. Here we advanced IACS-010759, a highly potent and selective small-molecule complex I inhibitor, into two dose-escalation phase I trials in patients with relapsed/refractory acute myeloid leukemia (NCT02882321, n = 17) and advanced solid tumors (NCT03291938, n = 23). The primary endpoints were safety, tolerability, maximum tolerated dose and recommended phase 2 dose (RP2D) of IACS-010759.