Modulation Of Signaling Pathways Research Articles

Cytotoxic effects of bee venom-loaded ZIF-8 nanoparticles on thyroid cancer cells: a promising strategy for targeted therapy.

Thyroid cancer continues to be a notable health issue, requiring the creation of novel treatment methods to enhance patient results. The objective of this study is to investigate the potential of utilizing bee venom (BV)-loaded zeolitic imidazolate framework-8 (ZIF-8) nanoparticles as a novel strategy for specifically targeting and treating medullary thyroid cancer cells. Due to their wide surface area and configurable pore size, ZIF-8 nanoparticles are ideal for drug delivery. Bee venom's cytotoxic capabilities are used in ZIF-8 nanoparticles to target thyroid cancer cells more effectively. ZIF-8 nanoparticles containing bee venom were tested on TT medullary thyroid cancer cell lines. The effects of these nanoparticles on cell viability, proliferation, and apoptosis were investigated. IC50 value at 24h for BV-ZIF-8 nanoparticles in TT medullary thyroid carcinoma cells was determined to be 17.19µg/mL, while the IC50 value at 48h was determined to be 16.39µg/mL. It has been demonstrated that nanoparticle treatment upregulates the Bax and caspase-3 genes while downregulating the Bcl-2, CCND1, and CDK4 genes. Additionally, it was observed that oxidative stress was triggered in the nanoparticle-treated group. Furthermore, an examination of its mechanisms was conducted, with a specific emphasis on the modulation of critical signaling pathways that are implicated in the progression of cancer. In thyroid cancer cells, ZIF-8 nanoparticles infused with bee venom promote programmed cell death and impair key biological processes.

Exploring Beta-sitosterol’s Role in Breast Cancer Treatment via Integrated Network Pharmacological Analysis and In Vitro Validation

Background Beta-sitosterol, a phytosterol similar to cholesterol, is found in various plants and is recognized for its potential anticancer properties; still, the mechanism of breast cancer (BC) remains elusive. Purpose This study investigates the potential targets of beta-sitosterol in BC using network pharmacological analysis and in vitro validation. Methods Targets of beta-sitosterol and BC were identified from online databases, including Swiss Target Prediction, SuperPred, GeneCards, and DisGeNET. Protein–protein interactions of common targets were analyzed using STRING version 11.0, and network construction and core target screening were performed with Cytoscape 3.8.0. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and gene ontology (GO) annotation were conducted using the ShinyGO web tool. Molecular docking analysis was done with AutoDock Vina and the in vitro validation, including cell viability, apoptosis, and gene expression analysis was done using MTT assay, acridine orange/ethidium bromide staining, and polymerase chain reaction (PCR), respectively. Results Sixty-eight common targets for beta-sitosterol and BC were identified from 209 beta-sitosterol targets and 1,350 BC-related genes. Five core targets (HIF1A, ESR1, STAT3, TNF, and MAPK3) were identified. GO analysis linked common targets to biological processes, cellular components, and molecular functions. KEGG pathway analysis showed enrichment in pathways such as central carbon metabolism in cancer, vascular endothelial growth factor signaling, and prolactin signaling. Beta-sitosterol’s impact on MCF7 cell viability was assessed via MTT assay, and its molecular effects were explored through PCR. Results demonstrated beta-sitosterol’s ability to hinder tumor progression by modulating genes involved in ESR1, mitogen-activated protein kinase, and tumor necrosis factor signaling pathways. Conclusion These findings highlight beta-sitosterol’s potential as an anticancer agent, offering new perspectives for clinical investigations through the modulation of key signaling pathways in BC.

Prognostic and Immunologic Significance of SH2B2 in Colon Adenocarcinoma and its Relationship to Proliferation, Migration, and Invasion.

SH2B adaptor protein 2 (SH2B2, also named APS) is an adaptor protein implicated in the modulation of insulin signaling pathways and glucose metabolism. Its role in colon adenocarcinoma (COAD) is unknown. Data from The Cancer Genome Atlas and Gene Expression Omnibus database were utilized to assess SH2B2 expression and its clinical significance in COAD. We investigated the associations between SH2B2 expression with genomic instability, tumor mutational burden (TMB), DNA methylation, alternative splicing, immune infiltration, and drug sensitivity. A SH2B2 knockdown model was developed to examine its impact on COAD cellular functions. Highly expressed SH2B2 is associated with a poorer prognosis in COAD. SH2B2 expression in COAD is associated with copy number variations, microsatellite instability, methylation patterns, and alternative 5' splicing events, but not with TMB. SH2B2 is positively correlated with mostly immune cells and the expression of PD-1 and CTLA4. The IC50 values of ten drugs were significantly correlated with SH2B2 expression. BI-2536_1086 had a strong binding affinity with SH2B2. Furthermore, the knockdown of SH2B2 reduced the proliferation, migration, and invasion of COAD cells. SH2B2 appears to act as an oncogene in COAD and may serve as a pivotal prognostic and therapeutic target, deserving further exploration.

Comprehensive Biotechnological Strategies for Podophyllotoxin Production from Plant and Microbial Sources.

Podophyllotoxin is derived from plant sources and exhibits strong anticancer activity. However, limited natural availability and environmental impacts from traditional extraction methods drive the search for alternative production approaches. This review explores diverse strategies for sustainable podophyllotoxin synthesis, including biosynthesis, semi-synthesis, and biotransformation. Biosynthetic methods involve metabolic pathway engineering in plant or microbial cells, enabling increased yields by manipulating precursor availability and gene expression. Semi-synthetic approaches modify podophyllotoxin precursors or intermediates to enhance therapeutic effects, with derivatives like etoposide and teniposide showing clinical efficacy. Biotransformation, utilizing organisms such as endophytic fungi or human hepatic enzymes, enables the transformation of substrates like deoxypodophyllotoxin into podophyllotoxin or its derivatives, yielding compounds with reduced environmental impact and improved purity. The anticancer efficacy of podophyllotoxin and its derivatives stems from multiple mechanisms. These compounds disrupt cell mitosis by inhibiting microtubule assembly, impairing nucleoside transport, and blocking topoisomerase II activity, leading to DNA cleavage and cancer cell apoptosis. Podophyllotoxin and its derivatives also exhibit anti-angiogenesis and anti-metastatic effects through signalling pathway modulation. Notably, derivatives like deoxypodophyllotoxin utilize advanced delivery systems, enhancing targeted efficacy and reducing side effects. Given the varied mechanisms and growing therapeutic applications, optimizing biotransformation and delivery techniques remains essential for advancing podophyllotoxin-based therapies. This comprehensive review underscores the compound's potential as a robust anticancer agent and the need for continued research to maximize its production and clinical effectiveness.

Loss in Pluripotency Markers in Mesenchymal Stem Cells upon Infection with Chlamydia trachomatis.

The intracellular pathogen Chlamydia trachomatis can inflict substantial damage on the host. Notably, Chlamydia infection is acknowledged for its precise modulation of diverse host signaling pathways to ensure cell survival, a phenomenon intricately connected to genetic regulatory changes in host cells. To monitor shifts in gene regulation within Chlamydia-infected cells, we employed mesenchymal stem cells (MSCs) as a naïve, primary cell model. Utilizing biochemical methods and imaging, our study discloses that acute Chlamydia infection in human MSCs leads to the downregulation of transcription factors Oct4, Sox2, and Nanog, suggesting a loss of pluripotency markers. Conversely, pluripotency markers in MSCs were sustained through treatment with conditioned medium from infected MSCs. Additionally, there is an augmentation in alkaline phosphatase activity, along with elevated Sox9 and CD44 mRNA expression levels observed during acute infection. A comprehensive screening for specific cell markers using touchdown PCR indicates an upregulation of mRNA for the early chondrogenesis gene Sox9 and a decrease in mRNA for the MSC marker vimentin. Real-time PCR quantification further corroborates alterations in gene expression, encompassing increased Sox9 and CD44 mRNA levels, alongside heightened alkaline phosphatase activity. In summary, the infection of MSCs with C. trachomatis induces numerous genetic deregulations, implying a potential trend towards differentiation into chondrocytes. These findings collectively underscore a targeted impact of Chlamydia on the gene regulations of host cells, carrying significant implications for the final fate and differentiation of these cells.

Investigating the Potential Effects of 6PPDQ on Prostate Cancer Through Network Toxicology and Molecular Docking

(1) Background: N-(1,3-Dimethylbutyl)-N′-phenyl-p-phenylenediamine-quinone (6PPDQ), as a newly discovered environmental toxin, has been found more frequently in our living conditions. The literature reports that damage to the reproductive and cardiovascular system is associated with exposure to 6PPDQ. However, the relationship between 6PPDQ and cancer still requires more investigation. This research aims to investigate the association between 6PPDQ and prostate cancer. (2) Methods and Results: Based on the data retrieved from the Pharmmapper, CTD, SEA, SwissTargetPrediction, GeneCard, and OMIM databases, we summarized 239 potential targets utilizing the Venn tool. Through the STRING network database and Cytoscape software, we constructed a PPI network and confirmed ten core targets, including IGF1R, PIK3R1, PTPN11, EGFR, SRC, GRB2, JAK2, SOS1, KDR, and IRS1. We identified the potential pathways through which 6PPDQ acts on these core targets using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Ultimately, through molecular docking methods, 6PPDQ binds closely with these ten core targets. These findings indicate that 6PPDQ may influence the proteins related to prostate cancer and may be linked to prostate cancer via several known signaling pathways. (3) Conclusions: This article employs innovative network toxicology to elucidate the prostate carcinogenic effects of 6PPDQ through its modulation of specific vital genes and signaling pathways, thereby establishing a foundational platform for future investigations into the impact of 6PPDQ on prostate cancer and potentially other tumors.

Evaluation of Antifibrotic Mechanisms of 3′5-Dimaleamylbenzoic Acid on Idiopathic Pulmonary Fibrosis: A Network Pharmacology and Molecular Docking Analysis

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic, disabling disorder of unknown etiology, poor prognosis, and limited therapeutic options. Previously, 3′5-dimaleamylbenzoic acid (3′5-DMBA) was shown to exert resolving effects in IPF, offering a promising alternative for treating this disease; however, the molecular mechanisms associated with this effect have not been explored. Objetive: We evaluated the potential antifibrotic mechanisms of 3′5-DMBA by network pharmacology (NP) and molecular docking (MD). Methods: 3′5-DMBA-associated targets were identified by screening in SwissTargetPrediction. IPF-associated targets were identified using lung tissue meta-analysis and public databases. Common targets were identified, and a protein–protein interaction (PPI) network was constructed; we ranked the proteins in the PPI network by topological analysis. MD validated the binding of 3′5-DMBA to the main therapeutic targets. Results: A total of 57 common targets were identified between 3′5-DMBA and IPF; caspase 8, 9, 3, and 7; myeloid leukemia-induced cell differentiation protein Mcl-1; and poly [ADP-ribose] polymerase 1 are primary targets regulating PPI networks. Functional analysis revealed that the common targets are involved in the pathological features of tissue fibrosis and primarily in the apoptotic process. MD revealed favorable interaction energies among the three main targets regulating PPI networks. Conclusions: NP results suggest that the antifibrotic effect of 3′5-DMBA is due to its regulation of the pathological features of IPF, mainly by modulating signaling pathways leading to apoptosis, suggesting its therapeutic potential to treat this disease.

Urinary microbiome profiling as a non-invasive tool for identifying biomarkers in systemic lupus erythematosus and lupus nephritis.

Bacteriome alterations have been implicated in the pathogenesis of systemic lupus erythematosus (SLE). However, the relationship between SLE and the urinary microbiome remains underexplored. This study aimed to characterize the urinary microbiome of SLE patients using 16S rRNA sequencing and to investigate its correlations with clinical parameters through integrative analyses. Urine sediment samples were collected from individuals with SLE and lupus nephritis (LN) (n = 20), SLE without LN (n = 22), and healthy controls (HCs) (n = 23). DNA was extracted and subjected to 16S rRNA sequencing to profile the urinary microbiome. Receiver operating characteristic (ROC) curve analysis was conducted to evaluate the diagnostic efficacy of urinary microbiota, while Spearman's correlation analysis was employed to identify links between specific microbial taxa and clinical parameters. Functional predictions of bacterial roles were performed using Picrust2. The urinary microbiota diagnostic model exhibited excellent performance in distinguishing SLE patients from HCs. Spearman's analysis revealed significant correlations between the urinary microbiome and clinical parameters. Specifically, Sphingomonas and Lachnospiraceae genera showed positive correlations with vitamin D levels, cylinderuria, and proteinuria, while Pedobacter, Aquabacterium, Delftia, and Achromobacter displayed negative correlations with proteinuria and albumin-to-creatinine ratio (ACR). Functional predictions indicated that the urinary microbiome might influence immune regulation through modulation of signaling pathways and metabolic processes. Our study is the first to reveal dysbiosis in the urinary microbiome of patients with SLE. Certain bacterial taxa in the urinary microbiome were identified as potential diagnostic biomarkers for SLE. Furthermore, the functional implications of these bacterial communities suggest their involvement in immune modulation, highlighting the potential for further investigation into their roles in SLE pathogenesis and diagnosis.

The role of curcumin in modulating circular RNAs and long non-coding RNAs in cancer.

Cancer is one of the primary causes of human disease and death, with high morbidity and mortality rates. Chemotherapy, one of the most common therapeutic techniques, functions through a variety of mechanisms, including the production of apoptosis and the prevention of tumor development. Herbal medicine has been the subject of numerous investigations due to its potential as a valuable source of innovative anti-cancer products that target multiple protein targets and cancer cell genomes. Curcumin, a polyphenol that is the major bioactive ingredient of turmeric, exhibits pharmacological and biological efficacy with antioxidant, anti-inflammatory, anticancer, cardioprotective, neuroprotective, and hypoglycemic activity in humans and animals. Recent research suggests that curcumin changes noncoding RNA (ncRNA), such as long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs), in various types of cancers. Both circRNAs and lncRNAs are ncRNAs that can epigenetically modulate the expression of multiple genes via post-transcriptional regulation. In this study, we outline curcumin's activities in modulating signaling pathways and ncRNAs in various malignancies. We also described curcumin's regulatory function, which involves blocking carcinogenic lncRNAs and circRNAs while increasing tumor-suppressive ones. Furthermore, we intend to demonstrate how ncRNAs and signaling pathways interact with each other across regulatory boundaries to gain a better understanding of how curcumin fights cancer and create a framework for its potential future therapeutic uses.

Modulation of the central nervous system immune response and neuroinflammation via Wnt signaling in health and neurodegenerative diseases

AbstractThe immune response in the central nervous system (CNS) is a highly specialized and tightly regulated process essential for maintaining neural health and protecting against pathogens and injuries. The primary immune cells within the CNS include microglia, astrocytes, T cells, and B cells. They work together, continuously monitor the CNS environment for signs of infection, injury, or disease, and respond by phagocytosing debris, releasing cytokines, and recruiting other immune cells. In addition to providing neuroprotection, these immune responses must be carefully balanced to prevent excessive inflammation that can lead to neuronal damage and contribute to neurodegenerative diseases. Dysregulated immune responses in the CNS are implicated in various neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Wnt signaling is a crucial pathway in the CNS that regulates various cellular processes critical for brain development, function, and maintenance. Despite enhancing immune responses in the health CNS, dysregulated Wnt signaling exacerbates neuroinflammation in the neurodegenerative brains. This review summarized the role of Wnt signaling in regulating immune response under different conditions. We then examined the role of immune response in healthy brains and during the development of neurodegenerative diseases. We also discussed therapeutic intervention in various neurodegenerative diseases through the modulation of the Wnt signaling pathway and neuroinflammation and highlighted challenges and limitations in current clinical trials.

Sirtuins: Emergent Players in Tissue and Organ Regeneration

Sirtuins are a family of lysine deacetylases that regulate cellular homeostasis and energy sensing. Regeneration is the process that restores structural and functional homeostasis at the cellular, tissue, organ, and appendage levels. Several cellular processes, such as epithelial–mesenchymal transition (EMT), proliferation, migration, and differentiation, contribute to restoration after an injury. This review highlights the role of sirtuins in tissue, organ, and anatomical structure regeneration, showing how sirtuins modulate signalling pathways by deacetylating targets such as transcription factors. Furthermore, understanding the role of this protein family could help elucidate the molecular and cellular mechanisms underlying tissue regeneration, which may hold significant potential for fields such as regenerative medicine. The review compiles evidence suggesting that sirtuins are emerging factors in the regeneration of various organs (e.g., skin, liver, heart) and tissues (e.g., bone, muscle, cornea, spinal cord).

Ubiquitin proteasome system in cardiac fibrosis.

Cardiac fibrosis, including reactive fibrosis and replacement fibrosis, is a common pathological process in most cardiovascular diseases. The ubiquitin proteasome system (UPS) plays an important role in the development of fibrosis by mediating the degradation and synthesis of proteins involved in transforming growth factor-β (TGF-β)-dependent and TGF-β-independent fibrous pathways. This review aims to provide an overview of ubiquitinated and deubiquitinated molecules that participating in cardiac fibrosis, with the ultimate purpose to identify promising targets for therapeutic strategies. The UPS primarily impacts cardiac fibrosis through modulation of the TGF-β signaling pathway targeting key molecules involved, including the TGF-β receptors, Smad2/3/4 complexes, and inhibitory Smad7, thereby influencing fibrotic processes. In addition to its effect on TGF-β signaling, UPS also regulates pro-fibrotic pathways independent of TGF-β, including p53, AKT1-p38, and JNK1/2. Understanding these pathways is critical due to their involvement in diverse fibrotic mechanisms. The interplay between ubiquitination and deubiquitination of crucial pathways and molecules is pivotal in cardiac fibrosis and represents a promising area for identifying novel therapeutic targets. Different types of cardiac fibrosis involve distinct fibrotic pathways, leading to differential effects of E3 ligases and DUBs across various cardiac fibrotic diseases. Insights into UPS-mediated regulation of cardiac fibrosis provides potential anti-fibrotic therapeutic strategies, emphasizing the importance of targeting UPS components specific to the heart for effective therapy against cardiac fibrosis.

Natural Modulators of Key Signaling Pathways in Skin Inflammageing

Natural Modulators of Key Signaling Pathways in Skin Inflammageing

Therapeutic role of naringin in cancer: molecular pathways, synergy with other agents, and nanocarrier innovations.

Naringin, a flavanone glycoside found abundantly in citrus fruits, is well-known for its various pharmacological properties, particularly its significant anticancer effects. Research, both in vitro and in vivo, has shown that naringin is effective against several types of cancer, including liver, breast, thyroid, prostate, colon, bladder, cervical, lung, ovarian, brain, melanoma, and leukemia. Its anticancer properties are mediated through multiple mechanisms, such as apoptosis induction, inhibition of cell proliferation, cell cycle arrest, and suppression of angiogenesis, metastasis, and invasion, all while exhibiting minimal toxicity and adverse effects. Naringin's molecular mechanisms involve the modulation of essential signaling pathways, including PI3K/Akt/mTOR, FAK/MMPs, FAK/bads, FAKp-Try397, IKKs/IB/NF-κB, JNK, ERK, β-catenin, p21CIPI/WAFI, and p38-MAPK. Additionally, it targets several signaling proteins, such as Bax, TNF-α, Zeb1, Bcl-2, caspases, VEGF, COX-2, VCAM-1, and interleukins, contributing to its wide-ranging antitumor effects. The remarkable therapeutic potential of naringin, along with its favorable safety profile, highlights its promise as a candidate for cancer treatment. This comprehensive review examines the molecular mechanisms behind naringin's chemopreventive and anticancer effects, including its pharmacokinetics and bioavailability. Furthermore, it discusses advancements in nanocarrier technologies designed to enhance these characteristics and explores the synergistic benefits of combining naringin with other anticancer agents, focusing on improved therapeutic efficacy and drug bioavailability.

A Genome-Wide Characterization of Receptor-like Cytoplasmic Kinase IV Subfamily Members in Populus deltoides Identifies the Potential Role of PdeCRCK6 in Plant Osmotic Stress Responses.

The IV subfamily of receptor-like cytoplasmic kinase (RLCK-IV), known as calcium-binding receptor-like cytoplasmic kinases (CRCKs), plays a vital role in plant signal transduction, particularly in coordinating growth and responses to abiotic stresses. However, our comprehension of CRCK genes in Populus deltoides, a species characterized as fast-growing and pest-resistant but with drought intolerance, is limited. Here, we identify 6 members of the CRCK subfamily on a genome-wide scale in P. deltoides, denoted as PdeCRCK1-PdeCRCK6. An evolutionary and structural analysis revealed highly conserved kinase catalytic domains across all PdeCRCKs, characterized by calmodulin (CaM)-binding sites and serine (Ser)/threonine (Thr) phosphorylation sites. The cis-acting elements of promoters indicated the presence of responsive elements for plant hormones, abiotic stresses, and transcription factor binding sites, which is supported by the distinct transcriptional expression patterns of PdeCRCKs under abscisic acid (ABA), polyethylene glycol (PEG), and mannitol treatments. A transient overexpression of PdeCRCK3/5/6 in tobacco (Nicotiana benthamiana) leaves indicated their involvement in reactive oxygen species (ROS) scavenging, polyamine gene synthesis, and ABA signaling pathway modulation. Immunoprecipitation-Mass Spectrometry (IP-MS) and a yeast two-hybrid (Y2H) assay showed that PdeCRCK6 interacted with AAA-type ATPase proteins and ubiquitin, suggesting its potential function in being involved in chloroplast homeostasis and the 26S ubiquitin protease system. Taken together, these findings offer a comprehensive analysis of the RLCK-IV subfamily members in P. deltoides, especially laying a foundation for revealing the potential mechanism of PdeCRCK6 in response to osmotic stresses and accelerating the molecular design breeding of drought tolerance in poplar.

Based on network pharmacology and molecular docking, the mechanism of action of Chinese herbal compound on mycoplasma synovial sac of chicken was studied

Mycoplasma synoviae (MS) is a wall-less pathogen primarily transmitted through the respiratory tract, causing synovitis and airsacculitis in poultry, which leads to substantial economic losses in the poultry industry. China has a long-standing tradition of Chinese medicine with abundant medicinal resources, renowned for its safety, efficacy, and holistic regulatory effects. This study aims to screen a traditional Chinese medicine (TCM) compound with anti-inflammatory and immunoregulatory properties and preliminarily validate its in vitro efficacy against MS infections. Based on the research foundation of this experiment and findings from previous studies, this study utilized network pharmacology analysis and molecular docking techniques to identify the anti-inflammatory and immunoregulatory effects of traditional Chinese medicinal herbs, including Rhizoma Coptidis, Honeysuckle (Flos Lonicerae Japonicae), Radix Codonopsis, and Radix Glycyrrhizae.The primary active components and potential targets were identified using the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) and other platforms. Protein-protein interaction (PPI) networks, Gene Ontology (GO) functional annotation, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were employed to identify critical therapeutic targets. The AutoDock software was used for molecular docking between active components and core targets. Subsequently, in vitro experiments were conducted to validate the effects of key active components on MS targets. The analysis revealed that this TCM compound contains 122 active components, including flavonoids (e.g., quercetin, trimethylisoflavone), chromones (e.g., anti-inflammatory coumarin A), and triterpenes (e.g., glycyrrhizic acid B). These components act on 739 pharmacological targets, and Venn analysis identified 23 intersection targets related to MS. Further analysis indicated that STAT3, IL6, and IL1B were potential core targets. KEGG pathway enrichment analysis showed that MAPK, FoxO, and Toll-like receptor signaling pathways played critical roles in the pathology and treatment of MS, while GO analysis emphasized the significance of the NF-κB signaling pathway and VEGF receptor pathway in immune regulation, inflammation, and tissue repair. Molecular docking results demonstrated that lignans and quercetin in this TCM compound exhibited strong binding affinities to IL1B, IL6, and STAT3, potentially modulating these key targets to exert anti-inflammatory and immunoregulatory effects. In vitro experiments further validated the significant inhibitory effects of quercetin and glycyrrhizic acid on MS infection. The findings suggest that this TCM compound may exert therapeutic effects on MS infection by regulating targets such as CASP3, TLR4, STAT3, IL6, and IL1B, and modulating signaling pathways including MAPK, NF-κB, and FoxO.

Photoaging Protective Effects of Quercitrin Isolated from ‘Green Ball’ Apple Peel

Premature skin aging, also known as photoaging, refers to the changes in the structure and function of the skin caused by chronic sun exposure. The ultraviolet radiation in sunlight is one of the key factors that cause photoaging. Thus, matrix metalloproteinases (MMPs), transforming growth factor beta-1 (TGFB1), and nuclear factor kappa B (NF-κB) signaling can be an effective therapeutic strategy for ultraviolet B (UVB) exposure. In this study, we used human dermal fibroblast and mouse macrophage cells to identify the mediators of skin photoaging. Quercitrin isolated from ‘Green Ball’ apple peel was treated to UVB-irradiated fibroblast cells and lipopolysaccharide (LPS)-induced macrophages to identify the photoaging prevention effect of quercitrin. Genes that are associated with photoaging were determined by using enzyme-linked immunosorbent assay (ELISA), Western blot, and quantitative polymerase chain reaction (qPCR). Quercitrin increased the collagen biosynthesis in UVB-irradiated fibroblast cells via regulating MMPs, TIMP metallopeptidase inhibitor 1 (TIMP-1), TGFB1, hyaluronan synthase 2 (HAS2), and collagen type I alpha 1 chain (COL1A2). In addition, quercitrin regulated p-65, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2), and its mediators (prostaglandin E2 and nitric oxide), in the NF-κB signaling process, and it inhibited the production of cytokines in LPS-induced macrophages. These results indicate that quercitrin can improve photoaging damaged skin by regulating MMPs, TGFB1, and NF-κB signaling pathway modulators.

Anti-inflammatory Activity of Chlorogenic Acid and Call for Further Research

In recent years, phenolic acids have garnered considerable interest on account of their diverse biological, practical, and pharmacological effects. Chlorogenic Acid (CGA), presently referred to as 3-CQA, is the most prevalent isomer among caffeoylquinic acid isomers (3-, 4-, and 5-CQA). Among the naturally occurring phenolic acid compounds found in green coffee extracts and tea, it is one of the most readily accessible acids. Recent studies have demonstrated that chlorogenic acid exerts its anti-inflammatory effects via various mechanisms, including the inhibition of inflammatory mediators, demonstration of antioxidant activity, modulation of signaling pathways, and regulation of the immune system. Each of these mechanisms is essential for immune system regulation. Chlorogenic acid mitigates tissue injury and impedes the inflammatory response through mechanisms, including inhibition of pro-inflammatory chemical synthesis and activity, scavenging of free radicals, and modulation of immune cell functionality. Throughout this review article, we have methodically examined the advantageous contributions of CGA in relation to its origin, assimilation, metabolism, molecular mechanisms, mechanistic effects, and impact on various forms of inflammation.

ROS-responsive nanoparticles for bioimaging and treating acute lung injury by releasing dexamethasone and improving alveolar macrophage homeostasis

BackgroundAcute lung injury (ALI) triggers the activation of pulmonary macrophages, which in turn produce excessive amounts of reactive oxygen species (ROS).ResultsWe synthesized ROS-responsive red light-emitting carbon dots (RCMNs) that target lung macrophages, possess bioimaging capabilities, and efficiently eliminate intracellular ROS, thereby demonstrating anti-inflammatory effects for treating acute lung injury (ALI). In an LPS-induced ALI mouse model, RCMNs showed bioimaging and therapeutic potential, reducing lung damage and inflammation by targeting ROS-damaged tissue. RCMNs also improved alveolar macrophage activity, decreased inflammatory cytokines (TNF-α and IL-6), and enhanced survival in endotoxic shock, indicating their therapeutic potential for ALI. RNA-seq analysis revealed that RCMNs modulate signaling pathways related to calcium, TNF, and Toll-like receptors, highlighting their role in regulating inflammation and immune responses. Mechanistically, RCMNs alleviate inflammation in ALI by enhancing mitochondrial function in lung macrophages, as evidenced by improved mitochondrial morphology and membrane potential.ConclusionsThis protective effect is mediated through the regulation of intracellular Ca2+ levels and mitochondrial respiratory chain complexes, suggesting RCMNs as a therapeutic strategy for mitochondrial dysfunction in ALI.Graphical

Imatinib Impedes EMT and Notch Signalling by Inhibiting p300 Acetyltransferase in Breast Cancer Cells.

Breast cancer remains a leading cause of cancer-related mortality among women, with current therapeutic approaches often limited by resistance and recurrence, especially in aggressive subtypes like triple-negative breast cancer. Drug repurposing has emerged as a promising strategy to address these challenges. In this study, we investigate the potential of Imatinib, a repurposed tyrosine kinase inhibitor, to inhibit epithelial-mesenchymal transition (EMT) in breast cancer cells by modulating the Notch signalling pathway. Our findings reveal that Imatinib treatment leads to a significant reduction in cancer cell stemness, invasiveness, and migration potential, alongside decreased colony-forming ability. EMT reversal was marked by a 2.71-fold increase in E-cadherin expression, with concurrent downregulation of mesenchymal markers, including Fibronectin (1.78-fold) and Slug (2.15-fold). Mechanistically, Imatinib was found to inhibit p300 acetyltransferase activity, resulting in reduced levels of H3K18Ac and H3K27Ac, which in turn led to the downregulation of key Notch pathway proteins such as HES1 (2.94-fold), AKT (2.08-fold), and p21 (1.88-fold). These results highlight the ability of Imatinib to suppress EMT through modulation of the Notch signalling pathway, offering a novel therapeutic avenue for breast cancer treatment. Overall, Imatinib demonstrates considerable potential for repurposing in breast cancer management by targeting critical oncogenic pathways involved in EMT and cancer progression.