Nitric oxide water-driven immunogenic cell death: Unfolding mitochondrial dysfunction's role in sensitizing lung adenocarcinoma to ferroptosis and autophagic cell death.

Non-small cell lung cancer (NSCLC), particularly lung adenocarcinoma (LUAD), significantly influences cancer-related mortality and is frequently considered by poor therapeutic responses due to genetic alterations. Cancer cells possess an inclination to develop resistance to individual treatment modalities, thus it is necessary to investigate several pathways simultaneously to obtain insights that will aid in the establishment of improved therapeutic approaches. Exploring regulated cell death (RCD) mechanisms offers promising avenues to augment immunotherapy by reshaping the tumor microenvironment (TME). Here, we investigated the prospective of microwave plasma-infused nitric oxide water (NOW) to initiate immunogenic cell death (ICD) while concurrently modulating autophagy and ferroptosis signaling in LUAD-associated A549 cells. Plasma treatment results in stable NO species nitrite/nitrate (NO2-/NO3-) in the water, altering its physicochemical properties. Analysis of ICD markers reveals increased expression of damage-associated molecular patterns (DAMPs) at both protein and mRNA levels post-NOW exposure. Intracellular reactive oxygen and nitrogen species (RONS) accumulation suggests NO-mediated mitochondrial dysfunction, triggering autophagy induction. Flow cytometry and western blotting confirm alterations in autophagy regulators Beclin 1 and SQSTM1. Furthermore, NOW treatment induces lipid peroxidation and upregulates ferroptosis-associated genes, as determined by qRT-PCR. Transmission electron microscopy (TEM) imaging reveals autophagosome formation and loss of cristae structures, corroborating the occurrence of autophagy and ferroptosis. Our findings propose that NOW may considered as inducer of ICD and the stimulation of other RCD-related proteins may enhance the anti-tumor immunogenicity.

Evaluation of degradation efficacy and toxicity mitigation for 4-nitrophenol using argon and air-mixed argon plasma jets.

This paper investigates the effects of argon (Ar) and that of Ar mixed with ambient air (Ar-Air) cold plasma jets (CPJs) on 4-nitrophenol (4-NP) degradation using low input power. The introduction of ambient air into the Ar-Air plasma jet enhances ionization-driven processes during high-voltage discharge by utilizing nitrogen and oxygen molecules from ambient air, resulting in increased reactive oxygen and nitrogen species (RONS) production, which synergistically interacts with argon. This substantial generation of RONS establishes Ar-Air plasma jet as an effective method for treating 4-NP contamination in deionized water (DW). Notably, the Ar-Air plasma jet treatment outperforms that of the Ar jet. It achieves a higher degradation rate of 97.2% and a maximum energy efficiency of 57.3 gkW-1h-1, following a 6-min (min) treatment with 100 mgL-1 4-NP in DW. In contrast, Ar jet treatment yielded a lower degradation rate and an energy efficiency of 75.6% and 47.8 gkW-1h-1, respectively, under identical conditions. Furthermore, the first-order rate coefficient for 4-NP degradation was measured at 0.23 min-1 for the Ar plasma jet and significantly higher at 0.56 min-1 for the Ar-Air plasma jet. Reactive oxygen species, such as hydroxyl radical and ozone, along with energy from excited species and plasma-generated electron transfers, are responsible for CPJ-assisted 4-NP breakdown. In summary, this study examines RONS production from Ar and Ar-Air plasma jets, evaluates their 4-NP removal efficacy, and investigates the biocompatibility of 4-NP that has been degraded after plasma treatment.

Biocompatible plasma-treated liquids: A sustainable approach for decontaminating gastrointestinal-infection causing pathogens.

Nosocomial infections are a serious threat and difficult to cure due to rising antibiotic resistance in pathogens and biofilms. Direct exposure to cold atmospheric plasma (CAP) has been widely employed in numerous biological research endeavors. Nonetheless, plasma-treated liquids (PTLs) formulated with physiological solutions may offer additional benefits such as enhanced portability, and biocompatibility. Additionally, CAP-infused long-lived reactive oxygen and nitrogen species (RONS) such as nitrite (NO2-), nitrate (NO3-), and hydrogen peroxide (H2O2) can synergistically induce their antibacterial activity. Herein, we investigated those argon-plasma jet-treated liquids, including Ringer's lactate (RL), phosphate-buffered saline (PBS), and physiological saline, have significant antibacterial activity against nosocomial/gastrointestinal-causing pathogens, which might be due to ROS-mediated lipid peroxidation. Combining the conventional culture-based method with propidium iodide monoazide quantitative PCR (PMAxx™-qPCR) indicated that PTLs induce a minimal viable but non-culturable (VBNC) state and moderately affect culturable counts. Specifically, the PTL exposure resulted in pathogenicity dysfunction via controlling T3SS-related effector genes of S. enterica. Overall, this study provides insights into the effectiveness of PTLs for inducing ROS-mediated damage, controlling the virulence of diarrheagenic bacteria, and modulating homeostatic genes.

TFCP2 as a therapeutic nexus: unveiling molecular signatures in cancer.

Tumor suppressor genes and proto-oncogenes comprise most of the complex genomic landscape associated with cancer, with a minimal number of genes exhibiting dual-context-dependent functions. The transcription factor cellular promoter 2 (TFCP2), a pivotal transcription factor encoded by the alpha globin transcription factor CP2 gene, is a constituent of the TFCP2/grainyhead family of transcription factors. While grainyhead members have been extensively studied for their crucial roles in developmental processes, embryogenesis, and multiple cancers, the TFCP2 subfamily has been relatively less explored. The molecular mechanisms underlying TFCP2's involvement in carcinogenesis are still unclear even though it is a desirable target for cancer treatment and a therapeutic marker. This comprehensive literature review summarizes the molecular functions of TFCP2, emphasizing its involvement in cancer pathophysiology, particularly in the epithelial-mesenchymal transition and metastasis. It highlights TFCP2's critical function as a regulatory target and explores its potential as a prognostic marker for survival and inflammation in carcinomas. Its ambiguous association with carcinomas underlines the urgent need for an in-depth understanding to facilitate the development of more efficacious targeted therapeutic modality and diagnostic tools. This study aims to elucidate the multifaceted effects of TFCP2 regulation, through a comprehensive integration of the existing knowledge in cancer therapeutics. Furthermore, the clinical relevance and the inherent challenges encountered in investigating its intricate role in cancer pathogenesis have been discussed in this review.

Unlocking melanoma Suppression: Insights from Plasma-Induced potent miRNAs through PI3K-AKT-ZEB1 axis.

INTRODUCTION: Melanoma is a rare but highly malignant form of skin cancer. Although recent targeted and immune-based therapies have improved survival rates by 10-15%, effective melanoma treatment remains challenging. Therefore, novel, combinatorial therapy options such as non-thermal atmospheric pressure plasma (NTP) are being investigated to inhibit and prevent chemoresistance. Although several studies have reported the apoptotic and inhibitory effects of reactive oxygen species produced by NTP in the context of melanoma, the intricate molecular network that determines the role of microRNAs (miRNAs) in regulating NTP-mediated cell death remains unexplored. OBJECTIVES: This study aimed to explore the molecular mechanisms and miRNA networks regulated by NTP-induced oxidative stress in melanoma cells. METHODS: Melanoma cells were exposed to NTP and then subjected to high-throughput miRNA sequencing to identify NTP-regulated miRNAs. Various biological processes and underlying molecular mechanisms were assessed using Alamar Blue, propidium iodide (PI) uptake, cell migration, and clonogenic assays followed by qRT-PCR and flow cytometry. RESULTS: NTP exposure for 3 min was sufficient to modulate the expression of several miRNAs, inhibiting cell growth. Persistent NTP exposure for 5 min increased differential miRNA regulation, PI uptake, and the expression of genes involved in cell cycle arrest and death. qPCR confirmed that miR-200b-3p and miR-215-5p upregulation contributed to decreased cell viability and migration. Mechanistically, inhibiting miR-200b-3p and miR-215-5p in SK-2 cells enhancedZEB1, PI3K, and AKT expression, increasing cell proliferation and viability. CONCLUSION: This study demonstrated that NTP exposure for 5 min results in the differential regulation of miRNAs related to the PI3K-AKT-ZEB1 axis and cell cycle dysregulation to facilitate melanoma suppression.

Functional impact of non-coding RNAs in high-grade breast carcinoma: Moving from resistance to clinical applications: A comprehensive review.

Despite the recent advances in cancer therapy, triple-negative breast cancers (TNBCs) are the most relapsing cancer sub-type. It is partly due to their propensity to develop resistance against the available therapies. An intricate network of regulatory molecules in cellular mechanisms leads to the development of resistance in tumors. Non-coding RNAs (ncRNAs) have gained widespread attention as critical regulators of cancer hallmarks. Existing research suggests that aberrant expression of ncRNAs modulates the oncogenic or tumor suppressive signaling. This can mitigate the responsiveness of efficacious anti-tumor interventions. This review presents a systematic overview of biogenesis and down streaming molecular mechanism of the subgroups of ncRNAs. Furthermore, it explains ncRNA-based strategies and challenges to target the chemo-, radio-, and immunoresistance in TNBCs from a clinical standpoint.