Goa University

The mitogen-activated protein kinase (MAPK) signaling pathway plays a key role in regulating a number of cellular processes, including proliferation, differentiation, apoptosis, and cellular responses to stress. In cancer, abnormal activation of some or all pathways of the MAPK cascade, particularly the RAS/RAF/MEK/ERK and p38/JNK signaling pathways, is common across many cancers as well as in an equal or disproportional measure in tumor initiation and progression. In the context of the tumor microenvironment (TME), the MAPK pathway facilitates complex interactions between cancer cells, stroma, and immune and endothelial cells. These interactions allow for elements of tumorigenesis, such as driving angiogenesis, immune suppression, and remodeling of the extracellular matrix, to all contribute to tumor survival and invasion. Additionally, MAPK signaling programs the response to cytokines and growth factor secretion by the TME beyond direct cellular responses, ultimately remodeling the TME in a favorable way for tumorigenesis. While targeting components of MAPK-related pathways has shown promise in the clinic, intrinsic and acquired resistance continues to develop in response to drug therapy composed of compensatory convoluted signaling, the activation of alternate signaling pathways, and TME-induced secondary feedback response. Recent data demonstrate that immune- and stroma-derived signals within the TME can sustain MAPK activity even under pharmacologic inhibition, providing the complexity of achieving durable therapeutic responses. As a result, it is crucial to gain consideration of the connections between MAPK signaling and the TME that may impart for sensitive strategies to elicit sustained drug-resistant treatment responses. Integrative therapies that incorporate MAPK inhibitors in conjunction with immunotherapy approaches, anti-angiogenic therapies, or metabolic modulators are also an important therapeutic strategy to elicit these adaptive pathways. This review will summarize our current understanding of the complex role of MAPK signaling in the TME, as well as propose broad ideas and potential future manipulation of MAPK-coordinated TME approaches for novel, durable cancer therapies.

ABSTRACT A simple method for determining water content in organic compounds has been demonstrated using Proton Nuclear Magnetic Resonance ( 1 H‐NMR) Spectroscopy. The method has been successfully applied to measure water content in a diverse range of substances, including active pharmaceutical ingredients (APIs), sugar molecules, commercial building blocks, and various solvents. Comparative analyses with Karl Fischer titration (KFT) demonstrate high consistency with this NMR approach, confirming its reliability as an adaptable alternative for water content determination in organic compounds. The current technique offers rapid execution, requires very small sample quantities, accommodates diverse substrates, and enables quantification without precise analyte measurements.

Lung cancer ranks as the second most prevalent cancer worldwide and exhibits the highest mortality rate among all cancers. It primarily consists of two subtypes: non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), with NSCLC representing 80-85% of cases. The Wnt/β-catenin signaling pathway is crucial in lung cancer initiation, progression, metastasis, and chemoresistance. MicroRNAs (miRNAs), small non-coding RNAs, significantly influence the tumor microenvironment by modulating cancer cell proliferation, angiogenesis, and apoptosis through the targeting of specific genes. Depending on their targets, miRNAs can function as oncogenes or tumor suppressors, highlighting their potential as therapeutic targets. Additionally, miRNAs serve as novel biomarkers for cancer diagnosis. Understanding the key miRNAs involved in lung cancer and their interactions with pathways like Wnt is essential for developing new diagnostic and therapeutic approaches. This review focuses on how specific miRNAs affect the Wnt pathway's components and their roles in tumorigenesis, metastasis, and therapy resistance, emphasizing their potential as therapeutic targets in NSCLC. Ultimately, this review aims to improve clinical outcomes and facilitate personalized therapeutic approaches for this aggressive malignancy.

In this research, in vitro and in silico drug discovery approaches were used to evaluate the antibacterial potential of a few unexplored freshwater green algae, namely Oedogonium angustistomum, Ulothrix variabilis and Mougeotia pulchella, as well as their fatty acids and peptides. In an in vitroantimicrobial assessment, the methanol and methanol crude extracts of U. variabilis significantly inhibited the growth of S. aureus and E. coli, showing inhibition zones of 14 mm and 13 mm, respectively. However, in the antifungal experiment, all extracts, except petroleum benzine, showed excellent inhibitory effects on C. albicans and F. oxysporum, with zones of inhibition ranging from 7.33 mm to 18 mm and 40.00% to 51.33%, respectively. In the minimum inhibitory concentration analysis, the methanol extract of U. variabilis effectively reduced the viability of S. aureus at a dose of 30 [Formula: see text]g/mL. Molecular docking analysis showed that 2-(S-glutathionyl) acetyl glutathione, Endomorphin-2 and APGPR enterostatin had stronger binding affinities with all microbial proteins than fatty acids, with docking scores of –8.315 kcal/mol, –8.687 kcal/mol, –8.313 kcal/mol and –7.054 kcal/mol, respectively. In the MD simulations, all hit peptide-protein complexes showed excellent binding stability, with a stable RMSD range of ¡2.8 Å and binding strengths of up to 99% for the simulation of 200 ns. These findings suggest that the peptides identified in algae have the potential to control antimicrobial-resistant strains and opportunistic fungal pathogens. However, further research is needed to ensure the safety and efficacy of these peptide compounds in lab-to-clinical applications.