Role of interferon dependent and independent signaling pathways: Implications in cancer.

Interferons (IFNs) are a class of cytokines with potent antiviral and immunomodulatory properties that regulate the immune system through multiple signaling pathways. In cancer, IFNs are vital to both tumor-intrinsic and extrinsic mechanisms that affect the quality of antitumor immunity as well as response to cancer treatments, including immunotherapy. However, there is a need for a deeper and better understanding of the mechanisms by which IFNs elicit immune signalling in cancerous cells.

An Overview of the Unfolded Protein Response (UPR) and Autophagy Pathways in Human Viral Oncogenesis.

Autophagy and Unfolded Protein Response (UPR) can be regarded as the safe keepers of cells exposed to intense stress. Autophagy maintains cellular homeostasis, ensuring the removal of foreign particles and misfolded macromolecules from the cytoplasm and facilitating the return of the building blocks into the system. On the other hand, UPR serves as a shock response to prolonged stress, especially Endoplasmic Reticulum Stress (ERS), which also includes the accumulation of misfolded proteins in the ER.

Targeting KRAS and SHP2 signaling pathways for immunomodulation and improving treatment outcomes in solid tumors.

Historically, KRAS has been considered 'undruggable' inspite of being one of the most frequently altered oncogenic proteins in solid tumors, primarily due to the paucity of pharmacologically 'druggable' pockets within the mutant isoforms. However, pioneering developments in drug design capable of targeting the mutant KRAS isoforms especially KRAS-mutant cancers, have opened the doors for emergence of combination therapies comprising of a plethora of inhibitors targeting different signaling pathways. SHP2 signaling pathway, primarily known for activation of intracellular signaling pathways such as KRAS has come up as a potential target for such combination therapies as it emerged to be the signaling protein connecting KRAS and the immune signaling pathways and providing the link for understanding the overlapping regions of RAS/ERK/MAPK signaling cascade.

Factors affecting heterogeneity in breast cancer microenvironment: A narrative mini review.

Breast cancer (BC) heterogeneity is a key trait of BC tumors with crucial implications on tumorigenesis, diagnosis, and therapeutic modalities. It is influenced by tumor intrinsic features and by the tumor microenvironment (TME) composition of different intra-tumoral regions, which in turn affect cancer progression within patients. In this mini review, we will highlight the mechanisms that generate cancer heterogeneity in BC and how they affect the responses to cancer therapies.

Carry-over effect of artificial light at night on daytime mating activity in an ecologically important detritivore, the amphipod Gammarus pulex.

Artificial light at night (ALAN) is a growing environmental problem influencing the fitness of individuals through effects on their physiology and behaviour. Research on animals has primarily focused on effects on behaviour during the night, whereas less is known about effects transferred to daytime. Here, we investigated in the lab the impact of ALAN on the mating behaviour of an ecologically important freshwater amphipod, Gammarus pulex, during both daytime and nighttime.

Intravesical Contrast-Enhanced MRI: A Potential Tool for Bladder Cancer Surveillance and Staging.

This review article gives an overview of the current state of the art of bladder cancer imaging and then discusses in depth the scientific and technical merit of a novel imaging approach, tracing its evolution from murine cancer models to cancer patients. While the poor resolution of soft tissue obtained by widely available imaging options such as abdominal sonography and radiation-based CT leaves them only suitable for measuring the gross tumor volume and bladder wall thickening, dynamic contrast-enhanced magnetic resolution imaging (DCE MRI) is demonstrably superior in resolving muscle invasion. However, major barriers still exist in its adoption.

Does large volume of distribution of lidocaine masks its systemic uptake from bladder?

Purpose: To assess whether therapeutic and toxic effects of intravesical lidocaine are determined by coincident serum levels.

Material And Methods: Published clinical trials and case studies on instilled lidocaine 1-2% that reported serum lidocaine levels were analyzed using model independent pharmacokinetic equations to compute the absorbed dose fraction (F) for linear regression with the respective dwell times.

Results: Rapid absorption of intravesical lidocaine is evinced by the serum levels of 0.

Treating Lower Urinary Tract Symptoms in Older Adults: Intravesical Options.

This article provides an overview of the diagnosis and the treatment of lower urinary tract symptoms in older adults complicated by the neurodegenerative changes in the micturition reflex and further confounded by age-related decline in hepatic and renal clearance raising the propensity of adverse drug reactions. The first-line drug treatment for lower urinary tract symptoms, orally administered antimuscarinics, fails to reach the equilibrium dissociation constant of muscarinic receptors even at their maximum plasma concentration and tends to evoke a half-maximal response at a muscarinic receptor occupancy of just 0.206% in the bladder with a minimal difference from exocrine glands, which raises the adverse drug reaction risk.

Targets of Immune Escape Mechanisms in Cancer: Basis for Development and Evolution of Cancer Immune Checkpoint Inhibitors.

Immune checkpoint blockade (ICB) has emerged as a novel therapeutic tool for cancer therapy in the last decade. Unfortunately, a small number of patients benefit from approved immune checkpoint inhibitors (ICIs). Therefore, multiple studies are being conducted to find new ICIs and combination strategies to improve the current ICIs.

Insulin resistance is associated with increased circulating lipocalin-2 levels in polycystic ovary syndrome: a systematic review and meta-analysis.

Introduction: This meta-analysis was conducted to compare the circulating lipocalin-2 levels in polycystic ovary syndrome (PCOS).

Evidence Acquisition: Relevant studies were retrieved by online database and manual searching. The standardized mean differences (SMDs) with 95% confidence intervals (CIs) were obtained by a random-effects meta-analysis.

Interception of Nickel Hydride Species and Its Application in Multicomponent Reactions.

The hydrogen borrowing strategy is an economical method for the α-functionalization of ketones. While this strategy is extremely advantageous, it does not lend itself to the synthesis of β,β-disubstituted ketones. This can be achieved, if the in situ generated metal hydride can be intercepted with a nucleophilic coupling partner.

Pharmacological effects of D-Pinitol - A comprehensive review.

In recent years, the application of phytochemicals to prevent or treat diseases has received greater attention. These phytochemicals have little or no toxicity against healthy tissues and are thus considered as ideal compounds. An impressive number of modern drugs are obtained from natural sources based on their traditional value.

Can anticipatory supply chain decision making manage the pandemic's effect? A regime switching game.

The COVID-19 pandemic has shown that stock outs of essential items like hand sanitizers, tissue papers and other items of hygiene and daily use have been characteristic of a supply chain, especially immediately following a pandemic wave. Consequently, retailers have to indulge in substantial supplier management efforts to ensure product availability during a pandemic wave. Using a piecewise deterministic differential game, we model a scenario where, while anticipating a pandemic wave, a supplier decides on product availability efforts to ensure product availability under the impending threat of stock outs.

Potential Immunomodulatory Properties of Biologically Active Components of Spices Against SARS-CoV-2 and Pan β-Coronaviruses.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced COVID-19 has emerged as a defining global health crisis in current times. Data from the World Health Organization shows demographic variations in COVID-19 severity and lethality. Diet may play a significant role in providing beneficial host cell factors contributing to immunity against deadly SARS-CoV-2 pathogenesis.

C-H Alkylation of Aldehydes by Merging TBADT Hydrogen Atom Transfer with Nickel Catalysis.

Catalyst controlled site-selective C-H functionalization is a challenging but powerful tool in organic synthesis. Polarity-matched and sterically controlled hydrogen atom transfer (HAT) provides an excellent opportunity for site-selective functionalization. As such, the dual Ni/photoredox system was successfully employed to generate acyl radicals from aldehydes via selective formyl C-H activation and subsequently cross-coupled to generate ketones, a ubiquitous structural motif present in the vast majority of natural and bioactive molecules.

Identification of Gain and Loss of Function Missense Variants in MRGPRX2's Transmembrane and Intracellular Domains for Mast Cell Activation by Substance P.

The neuropeptide substance P (SP) contributes to neurogenic inflammation through the activation of human mast cells via Mas-related G protein-coupled receptor-X2 (MRGPRX2). Using pertussis toxins and YM-254890, we demonstrated that SP induces Ca mobilization and degranulation via both the Gαi and Gαq family of G proteins in rat basophilic leukemia (RBL-2H3) cells stably expressing MRGPRX2. To determine the roles of MRGPRX2's transmembrane (TM) and intracellular domains on SP-induced responses, we utilized information obtained from both structural modeling and naturally occurring MRGPRX2 missense variants.

N-end rule pathway inhibitor sensitizes cancer cells to antineoplastic agents by regulating XIAP and RAD21 protein expression.

Anticancer drugs exert their effects on cancer cells by deregulating many pathways linked to cell cycle, apoptosis, etc. but cancer cells gradually become resistive against anticancer drugs, thereby necessitating the development of newer generation anticancer molecules. N-end rule pathway has been shown to be involved in the degradation of many cell cycle and apoptosis-related proteins.

β-Arrestin2 expressed in mast cells regulates ciprofloxacin-induced pseudoallergy and IgE-mediated anaphylaxis.

The adapter protein β-arrestin2 inhibits Mrgprb2 and FcεRI-mediated mast cell degranulation to attenuate pseudo-allergy and anaphylaxis. Thus, targeting β-arrestin2 in mast cells could provide novel therapeutic options for modulating pseudo-allergy and anaphylaxis.

Dopamine Cytotoxicity on SH-SY5Y Cells: Involvement of α-Synuclein and Relevance in the Neurodegeneration of Sporadic Parkinson's Disease.

The cytotoxicity of dopamine on cultured cells of neural origin has been used as a tool to explore the mechanisms of dopaminergic neurodegeneration in Parkinson's disease. In the current study, we have shown that dopamine induces a dose-dependent (10-40 μM) and time-dependent (up to 96 h) loss of cell viability associated with mitochondrial dysfunction and increased intra-cellular accumulation of α-synuclein in cultured SH-SY5Y cells. Dopamine-induced mitochondrial dysfunction and the loss of cell viability under our experimental conditions could be prevented by cyclosporine, a blocker of mitochondrial permeability transition pore, as well as the antioxidant N-acetylcysteine.

Angiogenic Host Defense Peptide AG-30/5C and Bradykinin B Receptor Antagonist Icatibant Are G Protein Biased Agonists for MRGPRX2 in Mast Cells.

AG-30/5C is an angiogenic host defense peptide that activates human mast cells (MC) via an unknown mechanism. Using short hairpin RNA-silenced human MC line LAD2 and stably transfected RBL-2H3 cells, we demonstrate that AG-30/5C induces MC degranulation via Mas-related G protein-coupled receptor X2 (MRGPRX2). Most G protein-coupled receptors signal via parallel and independent pathways mediated by G proteins and β-arrestins.

On the making of aromatic organometallic superalkali complexes.

Superalkalis are complexes that have a lower ionization energy than that of the corresponding alkali and alkaline earth metals. Based on First Principles calculations, the plausible existence of a superalkali complex consisting of an all-metal aromatic trigonal Au3 core coupled with pyridine (Py) and imidazole (IMD) ligands is suggested. The calculated ionization energy (IE) values of the subsequent organometallic complexes, Au3(Py)3 and Au3(IMD)3, are low, thereby mimicking the usual behavior of a superalkali.

Oestrogen receptor-mediated liposomal drug delivery for treating melanoma.

Function of steroid hormone oestrogen that transactivates oestrogen receptor (ER) is expressed in multiple organs. Except for malignancies of gynaecological organs, ER remains largely unutilised as a target to treat cancers of ER-expressing brain, prostate, skin etc. We have previously developed oestrogen targeting cationic lipid molecule (ES-C10), which showed targeted killing of ER + breast and skin cancer cells.

Ceramide and Sphingosine-1-Phosphate in Cell Death Pathways : Relevance to the Pathogenesis of Alzheimer's Disease.

The metabolic turnover of sphingolipids produces several signaling molecules that profoundly affect the proliferation, differentiation and death of cells. In particular, an enormous body of information is available that defines the varied role of ceramide and sphingosine-1-phosphate in cell death and survival. This review specifically examines the role of ceramide and sphingosine-1- phosphate in triggering neuronal death in Alzheimer's disease by analyzing the data from post-mortem studies and experimental research.