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.

Cold Atmospheric Pressure Plasma Solutions for Sustainable Food Packaging.

Increasing the number of resistant bacteria resistant to treatment is one of the leading causes of death worldwide. These bacteria are created in wounds and injuries and can be transferred through hospital equipment. Various attempts have been made to treat these bacteria in recent years, such as using different drugs and new sterilization methods. However, some bacteria resist drugs, and other traditional methods cannot destroy them. In the meantime, various studies have shown that cold atmospheric plasma can kill these bacteria through different mechanisms, making cold plasma a promising tool to deactivate bacteria. This new technology can be effectively used in the food industry because it has the potential to inactivate microorganisms such as spores and microbial toxins and increase the wettability and printability of polymers to pack fresh and dried food. It can also increase the shelf life of food without leaving any residue or chemical effluent. This paper investigates cold plasma's potential, advantages, and disadvantages in the food industry and sterilization.

Tobacco smoking is associated with combined pulmonary fibrosis and emphysema and worse outcomes in interstitial lung disease.

Tobacco smoking is an established cause of pulmonary disease whose contribution to interstitial lung disease (ILD) is incompletely characterized. We hypothesized that compared with nonsmokers, subjects who smoked tobacco would differ in their clinical phenotype and have greater mortality. We performed a retrospective cohort study of tobacco smoking in ILD. We evaluated demographic and clinical characteristics, time to clinically meaningful lung function decline (LFD), and mortality in patients stratified by tobacco smoking status (ever vs. never) within a tertiary center ILD registry (2006-2021) and replicated mortality outcomes across four nontertiary medical centers. Data were analyzed by two-sided t tests, Poisson generalized linear models, and Cox proportional hazard models adjusted for age, sex, forced vital capacity (FVC), diffusion capacity of the lung for carbon monoxide (DLCO), ILD subtype, antifibrotic therapy, and hospital center. Of 1,163 study participants, 651 were tobacco smokers. Smokers were more likely to be older, male, have idiopathic pulmonary fibrosis (IPF), coronary artery disease, CT honeycombing and emphysema, higher FVC, and lower DLCO than nonsmokers (P < 0.01). Time to LFD in smokers was shorter (19.7 ± 20 mo vs. 24.8 ± 29 mo; P = 0.038) and survival time was decreased [10.75 (10.08-11.50) yr vs. 20 (18.67-21.25) yr; adjusted mortality HR = 1.50, 95%CI 1.17-1.92; P < 0.0001] compared with nonsmokers. Smokers had 12% greater odds of death for every additional 10 pack yr of smoking (P < 0.0001). Mortality outcomes remained consistent in the nontertiary cohort (HR = 1.51, 95%CI = 1.03-2.23; P = 0.036). Tobacco smokers with ILD have a distinct clinical phenotype strongly associated with the syndrome of combined PF and emphysema, shorter time to LFD, and decreased survival. Smoking prevention may improve ILD outcomes.NEW & NOTEWORTHY Smoking in ILD is associated with combined pulmonary fibrosis and emphysema and worse clinical outcomes.

Cold Atmospheric Pressure Plasma: A Growing Paradigm in Diabetic Wound Healing-Mechanism and Clinical Significance.

Diabetes is one of the most significant causes of death all over the world. This illness, due to abnormal blood glucose levels, leads to impaired wound healing and, as a result, foot ulcers. These ulcers cannot heal quickly in diabetic patients and may finally result in amputation. In recent years, different research has been conducted to heal diabetic foot ulcers: one of them is using cold atmospheric pressure plasma. Nowadays, cold atmospheric pressure plasma is highly regarded in medicine because of its positive effects and lack of side effects. These conditions have caused plasma to be considered a promising technology in medicine and especially diabetic wound healing because studies show that it can heal chronic wounds that are resistant to standard treatments. The positive effects of plasma are due to different reactive species, UV radiation, and electromagnetic fields. This work reviews ongoing cold atmospheric pressure plasma improvements in diabetic wound healing. It shows that plasma can be a promising tool in treating chronic wounds, including ones resulting from diabetes.

Plasma-Generated Nitric Oxide Water Mediates Environmentally Transmitted Pathogenic Bacterial Inactivation via Intracellular Nitrosative Stress.

Over time, the proportion of resistant bacteria will increase. This is a major concern. Therefore, effective and biocompatible therapeutic strategies against these bacteria are urgently needed. Non-thermal plasma has been exhaustively characterized for its antibacterial activity. This study aims to investigate the inactivation efficiency and mechanisms of plasma-generated nitric oxide water (PG-NOW) on pathogenic water, air, soil, and foodborne Gram-negative and Gram-positive bacteria. Using a colony-forming unit assay, we found that PG-NOW treatment effectively inhibited the growth of bacteria. Moreover, the intracellular nitric oxide (NO) accumulation was evaluated by 4-amino-5-methylamino-2',7'-dichlorofluorescein diacetate (DAF-FM DA) staining. The reduction of viable cells unambiguously indicates the anti-microbial effect of PG-NOW. The soxR and soxS genes are associated with nitrosative stress, and oxyR regulation corresponds to oxidative stress in bacterial cells. To support the nitrosative effect mediated by PG-NOW, we have further assessed the soxRS and oxyR gene expressions after treatment. Accordingly, soxRS expression was enhanced, whereas the oxyR expression was decreased following PG-NOW treatment. The disruption of cell morphology was observed using scanning electron microscopy (SEM) analysis. In conclusion, our findings furnish evidence of an initiation point for the further progress and development of PG-NOW-based antibacterial treatments.

Nanocarrier cancer therapeutics with functional stimuli-responsive mechanisms.

Presently, nanocarriers (NCs) have gained huge attention for their structural ability, good biocompatibility, and biodegradability. The development of effective NCs with stimuli-responsive properties has acquired a huge interest among scientists. When developing drug delivery NCs, the fundamental goal is to tackle the delivery-related problems associated with standard chemotherapy and to carry medicines to the intended sites of action while avoiding undesirable side effects. These nanocarriers were able of delivering drugs to tumors through regulating their pH, temperature, enzyme responsiveness. With the use of nanocarriers, chemotherapeutic drugs could be supplied to tumors more accurately that can equally encapsulate and deliver them. Material carriers for chemotherapeutic medicines are discussed in this review keeping in viewpoint of the structural properties and targeting methods that make these carriers more therapeutically effective, in addition to metabolic pathways triggered by drug-loaded NCs. Largely, the development of NCs countering to endogenous and exogenous stimuli in tumor regions and understanding of mechanisms would encourage the progress for tumor therapy and precision diagnosis in future.

Current Nanomedicine for Targeted Vascular Disease Treatment: Trends and Perspectives.

Nanotechnology has been developed to deliver cargos effectively to the vascular system. Nanomedicine is a novel and effective approach for targeted vascular disease treatment including atherosclerosis, coronary artery disease, strokes, peripheral arterial disease, and cancer. It has been well known for some time that vascular disease patients have a higher cancer risk than the general population. During atherogenesis, the endothelial cells are activated to increase the expression of adhesion molecules such as Intercellular Adhesion Molecule 1 (ICAM-1), Vascular cell adhesion protein 1 (VCAM-1), E-selectin, and P-selectin. This biological activation of endothelial cells gives a targetability clue for nanoparticle strategies. Nanoparticle formation has a passive targeting pathway due to the increased adhesion molecule expression on the cell surface as well as increased cell activation. In addition, the VCAM-1-targeting peptide has been widely used to target the inflamed endothelial cells. Biomimetic nanoparticles using platelet and leukocyte membrane fragment strategies have been promising techniques for targeted vascular disease treatment. Cyclodextrin, a natural oligosaccharide with a hydrophobic cavity, increase the solubility of cholesterol crystals at the atherosclerotic plaque site and has been used to deliver the hydrophobic drug statin as a therapeutic in a targeted manner. In summary, nanoparticles decorated with various targeting molecules will be an effective and promising strategy for targeted vascular disease treatment.

Periodic Exposure of Plasma-Activated Medium Alters Fibroblast Cellular Homoeostasis.

Excess amounts of redox stress and failure to regulate homeostatic levels of reactive species are associated with several skin pathophysiologic conditions. Nonmalignant cells are assumed to cope better with higher reactive oxygen and nitrogen species (RONS) levels. However, the effect of periodic stress on this balance has not been investigated in fibroblasts in the field of plasma medicine. In this study, we aimed to investigate intrinsic changes with respect to cellular proliferation, cell cycle, and ability to neutralize the redox stress inside fibroblast cells following periodic redox stress in vitro. Soft jet plasma with air as feeding gas was used to generate plasma-activated medium (PAM) for inducing redox stress conditions. We assessed cellular viability, energetics, and cell cycle machinery under oxidative stress conditions at weeks 3, 6, 9, and 12. Fibroblasts retained their usual physiological properties until 6 weeks. Fibroblasts failed to overcome the redox stress induced by periodic PAM exposure after 6 weeks, indicating its threshold potential. Periodic stress above the threshold level led to alterations in fibroblast cellular processes. These include consistent increases in apoptosis, while RONS accumulation and cell cycle arrest were observed at the final stages. Currently, the use of NTP in clinical settings is limited due to a lack of knowledge about fibroblasts' behavior in wound healing, scar formation, and other fibrotic disorders. Understanding fibroblasts' physiology could help to utilize nonthermal plasma in redox-related skin diseases. Furthermore, these results provide new information about the threshold capacity of fibroblasts and an insight into the adaptation mechanism against periodic oxidative stress conditions in fibroblasts.

Transcriptome Analysis of Insulin Signaling-Associated Transcription Factors in C. elegans Reveal Their Genome-Wide Target Genes Specificity and Complexity.

Insulin/IGF-1-like signaling (IIS) plays a crucial, conserved role in development, growth, reproduction, stress tolerance, and longevity. In Caenorhabditis elegans, the enhanced longevity under reduced insulin signaling (rIIS) is primarily regulated by the transcription factors (TFs) DAF-16/FOXO, SKN-1/Nrf-1, and HSF1/HSF-1. The specific and coordinated regulation of gene expression by these TFs under rIIS has not been comprehensively elucidated. Here, using RNA-sequencing analysis, we report a systematic study of the complexity of TF-dependent target gene interactions during rIIS under analogous genetic and experimental conditions. We found that DAF-16 regulates only a fraction of the C. elegans transcriptome but controls a large set of genes under rIIS; SKN-1 and HSF-1 show the opposite trend. Both of the latter TFs function as activators and repressors to a similar extent, while DAF-16 is predominantly an activator. For expression of the genes commonly regulated by TFs under rIIS conditions, DAF-16 is the principal determining factor, dominating over the other two TFs, irrespective of whether they activate or repress these genes. The functional annotations and regulatory networks presented in this study provide novel insights into the complexity of the gene regulatory networks downstream of the IIS pathway that controls diverse phenotypes, including longevity.

Strategies for Using Polydopamine to Induce Biomineralization of Hydroxyapatite on Implant Materials for Bone Tissue Engineering.

In the field of tissue engineering, there are several issues to consider when designing biomaterials for implants, including cellular interaction, good biocompatibility, and biochemical activity. Biomimetic mineralization has gained considerable attention as an emerging approach for the synthesis of biocompatible materials with complex shapes, categorized organization, controlled shape, and size in aqueous environments. Understanding biomineralization strategies could enhance opportunities for novel biomimetic mineralization approaches. In this regard, mussel-inspired biomaterials have recently attracted many researchers due to appealing features, such as strong adhesive properties on moist surfaces, improved cell adhesion, and immobilization of bioactive molecules via catechol chemistry. This molecular designed approach has been a key point in combining new functionalities into accessible biomaterials for biomedical applications. Polydopamine (PDA) has emerged as a promising material for biomaterial functionalization, considering its simple molecular structure, independence of target materials, cell interactions for adhesion, and robust reactivity for resulting functionalization. In this review, we highlight the strategies for using PDA to induce the biomineralization of hydroxyapatite (HA) on the surface of various implant materials with good mechanical strength and corrosion resistance. We also discuss the interactions between the PDA-HA coating, and several cell types that are intricate in many biomedical applications, involving bone defect repair, bone regeneration, cell attachment, and antibacterial activity.

Cold atmospheric plasma and silymarin nanoemulsion synergistically inhibits human melanoma tumorigenesis via targeting HGF/c-MET downstream pathway.

BACKGROUND: Recent studies claimed the important role of cold atmospheric plasma (CAP) with nanotechnology in cancer treatments. In this study, silymarin nanoemulsion (SN) was used along with air CAP as therapeutic agent to counter human melanoma. METHODS: In this study, we examined the combined treatment of CAP and SN on G-361 human melanoma cells by evaluating cellular toxicity levels, reactive oxygen and nitrogen species (RONS) levels, DNA damage, melanoma-specific markers, apoptosis, caspases and poly ADP-ribose polymerase-1 (PARP-1) levels using flow cytometer. Dual-treatment effects on the epithelial-mesenchymal transition (EMT), Hepatocyte growth factor (HGF/c-MET) pathway, sphere formation and the reversal of EMT were also assessed using western blotting and microscopy respectively. SN and plasma-activated medium (PAM) were applied on tumor growth and body weight and melanoma-specific markers and the mesenchymal markers in the tumor xenograft nude mice model were checked. RESULTS: Co-treatment of SN and air CAP increased the cellular toxicity in a time-dependent manner and shows maximum toxicity at 200 nM in 24 h. Intracellular RONS showed significant generation of ROS (< 3 times) and RNS (< 2.5 times) in dual-treated samples compared to control. DNA damage studies were assessed by estimating the level of γ-H2AX (1.8 times), PD-1 (> 2 times) and DNMT and showed damage in G-361 cells. Increase in Caspase 8,9,3/7 (> 1.5 times), PARP level (2.5 times) and apoptotic genes level were also observed in dual treated group and hence blocking HGF/c-MET pathway. Decrease in EMT markers (E-cadherin, YKL-40, N-cadherin, SNAI1) were seen with simultaneously decline in melanoma cells (BRAF, NAMPT) and stem cells (CD133, ABCB5) markers. In vivo results showed significant reduction in SN with PAM with reduction in tumor weight and size. CONCLUSIONS: The use of air CAP using µ-DBD and the SN can minimize the malignancy effects of melanoma cells by describing HGF/c-MET molecular mechanism of acting on G-361 human melanoma cells and in mice xenografts, possibly leading to suitable targets for innovative anti-melanoma approaches in the future.

Low dose radiation regulates BRAF-induced thyroid cellular dysfunction and transformation.

BACKGROUND: The existence of differentiated thyroid cells is critical to respond radioactive iodide treatment strategy in thyroid cancer, and loss of the differentiated phenotype is a trademark of iodide-refractive thyroid disease. While high-dose therapy has been beneficial to several cancer patients, many studies have indicated this clinical benefit was limited to patients having BRAF mutation. BRAF-targeted paired box gene-8 (PAX8), a thyroid-specific transcription factor, generally dysregulated in BRAF-mutated thyroid cancer. METHODS: In this study, thyroid iodine-metabolizing gene levels were detected in BRAF-transformed thyroid cells after low and high dose of ionizing radiation. Also, an mRNA-targeted approach was used to figure out the underlying mechanism of low (0.01Gyx10 or 0.1Gy) and high (2Gy) radiation function on thyroid cancer cells after BRAFV600E mutation. RESULTS: Low dose radiation (LDR)-induced PAX8 upregulation restores not only BRAF-suppressive sodium/iodide symporter (NIS) expression, one of the major protein necessary for iodine uptake in healthy thyroid, on plasma membrane but also regulate other thyroid metabolizing genes levels. Importantly, LDR-induced PAX8 results in decreased cellular transformation in BRAF-mutated thyroid cells. CONCLUSION: The present findings provide evidence that LDR-induced PAX8 acts as an important regulator for suppression of thyroid carcinogenesis through novel STAT3/miR-330-5p pathway in thyroid cancers.

Biological and medical applications of plasma-activated media, water and solutions.

Non-thermal atmospheric pressure plasma has been proposed as a new tool for various biological and medical applications. Plasma in close proximity to cell culture media or water creates reactive oxygen and nitrogen species containing solutions known as plasma-activated media (PAM) or plasma-activated water (PAW) - the latter even displays acidification. These plasma-treated solutions remain stable for several days with respect to the storage temperature. Recently, PAM and PAW have been widely studied for many biomedical applications. Here, we reviewed promising reports demonstrating plasma-liquid interaction chemistry and the application of PAM or PAW as an anti-cancer, anti-metastatic, antimicrobial, regenerative medicine for blood coagulation and even as a dental treatment agent. We also discuss the role of PAM on cancer initiation cells (spheroids or cancer stem cells), on the epithelial mesenchymal transition (EMT), and when used for metastasis inhibition considering its anticancer effects. The roles of PAW in controlling plant disease, seed decontamination, seed germination and plant growth are also considered in this review. Finally, we emphasize the future prospects of PAM, PAW or plasma-activated solutions in biomedical applications with a discussion of the mechanisms and the stability and safety issues in relation to humans.

Thiazides in the management of hypertension in older adults - a systematic review.

BACKGROUND: Thiazides are commonly prescribed to older people for the management of hypertension. The objective of this study was to identify the evidence on the risks and benefits of their use among adults aged ≥65 years and to develop recommendations to reduce potentially inappropriate use. METHODS: Systematic review (SR) of the literature covering six databases. We applied a staged search approach, where each search was undertaken only if the previous one did not yield high quality results. Searches 1 and 2 identified relevant SRs and meta-analyses published up to December 2015 from all databases. Search 3 identified additional individual interventional studies (IS) and observational studies (OS) not identified by the preceding searches. We included all studies evaluating the effect of thiazides on patient-relevant outcomes in the management of hypertension with a sufficient number of participants aged ≥65 years or a subgroup analysis based on age. Two independent reviewers extracted data and carried out quality appraisal. Recommendations were developed using the GRADE methodology. RESULTS: Searches 1 to 3 were performed. We included 34 articles reporting on 12 IS and 4 OS. Mean ages ranged from 59 to 83.8 years. Four studies had performed a subgroup analysis by age. Information on comorbidity, polypharmacy and frailty of the participants was scarce or not available. The IS compared thiazides to placebo or other antihypertensive drugs and evaluated cardiovascular endpoints or all-cause-mortality as primary outcomes. The OS investigated the association between thiazide use and the risk of gout, fractures and adverse effects. Our results suggest that thiazides are efficacious in preventing cardiovascular events for this population group. Low-dose regimens of thiazides may be safer than high-dose (low quality of evidence), and a history of gout may increase the risk of adverse events (low quality of evidence). Three recommendations were developed. CONCLUSIONS: The use of low dose treatment with thiazides for the management of hypertension in adults aged 65 and older seems justified, unless a history of gout is present. The quality of the evidence is low and studies rarely describe characteristics of the participants such as polypharmacy and frailty. Further good quality studies are needed.

Casamino acids facilitate the secretion of recombinant dengue virus serotype-3 envelope domain III in Pichia pastoris.

BACKGROUND: Dengue is a viral disease spread to humans by mosquitoes. Notably, there are four serotypes of dengue viruses (DENV) that places ~40 % of the global population at risk of infection. However, lack of a suitable drug or a preventive vaccine exacerbates the matter further. Envelope domain-III (EDIII) antigen of dengue virus (DENV) has garnered much attention as a promising vaccine candidate for dengue, in addition to its use as a diagnostic intermediate. Hence developing a method for efficient production of high quality recombinant EDIII is important for research and industrial purpose. RESULTS: In this work, a Pichia pastoris system was optimized for the secretory over-expression of DENV serotype-3 EDIII under the control of methanol inducible AOX1 promoter. Temperature alone had a significant impact upon the amount of secretory EDIII, with 2.5-fold increase upon reducing the induction temperature from 30 to 20 °C. However surprisingly, supplementation of culture media with Casamino acids (CA), further augmented secretory EDIII titer, with a concomitant drop of intracellular EDIII levels at both temperatures. Though, reduction in intracellular retention of EDIII was more prominent at 20 °C than 30 °C. This suggests that CA supplementation facilitates overexpressing P. pastoris cells to secrete more EDIII by reducing the proportion retained intracellularly. Moreover, a bell-shaped correlation was observed between CA concentration and secretory EDIII titer. The maximum EDIII expression level of 187 mg/L was achieved under shake flask conditions with induction at 20 °C in the presence of 1 % CA. The overall increase in EDIII titer was ~9-fold compared to un-optimized conditions. Notably, mouse immune-sera, generated using this purified EDIII antigen, efficiently neutralized the DENV. CONCLUSIONS: The strategy described herein could enable fulfilling the mounting demand for recombinant EDIII as well as lay direction to future studies on secretory expression of recombinant proteins in P. pastoris with CA as a media supplement.

Novel aminoalkylated azaphenothiazines as potential inhibitors of T98G, H460 and SNU80 cancer cell lines in vitro.

A set of twenty-one novel aminoalkylated azaphenothiazines is synthesized using a two-step methodology starting from azaphenothiazines. The key step was the selective monoalkylation at position 10 of azaphenothiazines. In all, twenty-five molecules, including intermediates, were investigated for their in vitro anticancer activity, of which fourteen azaphenothiazines (2b, 3a, 3c, 3d, 3e-h, 3j, 3n, 3o, 3p, 3s, and 3u) were found to decrease the metabolic viability and growth of the T98G, H460 and SNU80 cancer cells effectively in a dose-dependent manner. In silico, pharmacokinetic studies suggest that these molecules have good bioavailability, water solubility and other drug-like parameters. Compounds 3a, 3c and 3g were identified as the leading molecules for future investigation due to their (a) high activity against T98G brain, H460 lung and SNU80 thyroid cancer cells; (b) low cytotoxicity with regard to non-malignant HEK293 and MRC5 cells; (c) low toxic risk levels based on in vitro and in silico evaluations; (d) good theoretical oral bioavailability according to Lipinski 'rule of five' pharmacokinetic parameters; and (e) better drug-likeness and drug-score values.

Biomedical and Clinical Importance of Mussel-Inspired Polymers and Materials.

The substance secreted by mussels, also known as nature's glue, is a type of liquid protein that hardens rapidly into a solid water-resistant adhesive material. While in seawater or saline conditions, mussels can adhere to all types of surfaces, sustaining its bonds via mussel adhesive proteins (MAPs), a group of proteins containing 3,4-dihydroxyphenylalanine (DOPA) and catecholic amino acid. Several aspects of this adhesion process have inspired the development of various types of synthetic materials for biomedical applications. Further, there is an urgent need to utilize biologically inspired strategies to develop new biocompatible materials for medical applications. Consequently, many researchers have recently reported bio-inspired techniques and materials that show results similar to or better than those shown by MAPs for a range of medical applications. However, the susceptibility to oxidation of 3,4-dihydroxyphenylalanine poses major challenges with regard to the practical translation of mussel adhesion. In this review, various strategies are discussed to provide an option for DOPA/metal ion chelation and to compensate for the limitations imposed by facile 3,4-dihydroxyphenylalanine autoxidation. We discuss the anti-proliferative, anti-inflammatory, anti-microbial activity, and adhesive behaviors of mussel bio-products and mussel-inspired materials (MIMs) that make them attractive for synthetic adaptation. The development of biologically inspired adhesive interfaces, bioactive mussel products, MIMs, and arising areas of research leading to biomedical applications are considered in this review.

Self-assembled supramolecular hetero-bimetallacycles for anticancer potency by intracellular release.

Two new tetracationic hetero-bimetallacycles, compounds 4 and 5, have been constructed from an N,N'-bis(4-(pyridin-4-ylethynyl)phenyl)pyridine-2,6-dicarboxamide ligand (1), and cis-blocked complexes [M(dppf)(OTf)2 ] (dppf=1,1'-bis(diphenylphosphino)ferrocene; OTf=trifluoromethanesulfonate; M=Pd (2), Pt (3)) in CH3 NO2 /CH2 Cl2 (1:1) solvent. Both complexes were isolated with adequate yields as triflate salts and were then characterized using (1) H, (13) C, and (31) P NMR spectroscopy, elemental analysis, UV/Vis spectroscopy, and high-resolution electrospray mass spectrometry (HR-ESMS). The molecular structure of 4 was determined by molecular mechanics force-field calculations. The cytotoxic effect of both new complexes were analyzed against T98G (brain tumor), KB (head and neck cancer), SNU-80 (thyroid cancer), and HEK-293 non-malignant cell lines. The cytotoxicity of complexes 4 and 5 were found to be considerably more effective against cancer cells than reference drug cisplatin. Annexin-V/PI staining, caspase-3/7 activity, and the reduction in mitochondrial membrane potential justify a significant level of apoptosis in complex-treated cells.

Surface air gas discharge plasma: An ecofriendly virus inactivation approach to enhance CPRRs mediated antiviral genes expression against airborne bio-contaminant (human Coronavirus-229E).

Emerging bio-contaminants (airborne viruses) exploits and manipulate host (human) metabolism to produce new viral particles, evading the host's immune defences and leading to infections. Non-thermal plasma, operating at atmospheric pressure and ambient temperature, is explored for virus inactivation, generating RONS that interact and denatures viral proteins. However, various factors affecting virus survival influence the efficacy of non-thermal plasma. Glucose analogue 2-DG, a metabolic modifier used in this study, disrupts the glycolysis pathway viruses rely on, creating an unfavourable environment for replication. Here, airborne HCoV-229E bio-contaminant was treated with plasma for inactivation, and the presence of RONS was analysed. Metabolically altered lung cells were subsequently exposed to the treated airborne viruses. Cytopathic effect, spike protein, and cell death were evaluated via flow cytometry and confocal microscopy, and CPRRs mediated antiviral gene expression was evaluated using PCR. Gas plasma-treated viruses led to reduced virus proliferation in unaltered lung cells, although few virus particles survived the exposure, as confirmed by biological assessment (cytopathic effects and live/dead staining). A combination approach of gas plasma-treated viruses and altered lung cells displayed drastic virus reduction compared to the control group, established through confocal microscopy and flow cytometry. Furthermore, altered lung cell enhances gene transcription responsible for innate immunity when exposed to the gas plasma-treated virus, thereby impeding airborne virus propagation. This study demonstrates the significance of a surface air gas plasma and metabolic alteration approach in enhancing genes targeted towards antiviral innate immunity and tackling outbreaks of emerging bio-contaminants of concerns (airborne viruses).

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.