Oxidative stress and inflammation: elucidating mechanisms of smoking-attributable pathology for therapeutic targeting

Bulletin of the National Research Centre/Bulletin of the National Research Center, Journal Year: 2024, Volume and Issue: 48(1)

Published: Jan. 22, 2024

Abstract Background Tobacco smoking remains a major preventable cause of disease and death worldwide. Combustible cigarettes release thousands chemicals that can initiate inflammatory pathways leading to smoking-related illness. This review aims synthesize current scientific knowledge on mechanisms smoking-induced disease, epidemiological trends, clinical strategies from recent literature. Main body the abstract At cellular level, cigarette smoke triggers oxidative stress through reactive oxygen species (ROS), causing DNA damage. provokes signaling cascades mediated by damage-associated molecular patterns (DAMPs), receptors like RAGE TLRs, downstream cytokines. Smoking also disrupts apoptosis autophagy. In lungs, inflammation play central roles in COPD pathogenesis. Smoking-induced damage, chronic inflammation, impaired immunity combine promote lung carcinogenesis. For cardiovascular endothelial dysfunction, platelet activation, atherogenesis oxidized LDL effects nitric oxide adhesion molecules. Short conclusion Given unequivocal evidence health risks, cessation is critical reducing disability. Both counseling pharmacotherapy have proven efficacy for quitting, but limited long-term. Emerging nicotine products e-cigarettes unknown impacts population health. Comprehensive efforts encompassing prevention, screening, treatment innovation, harm reduction, policy reform focused curbing smoking-attributable morbidity mortality are warranted.

Language: Английский

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Hepatocellular Carcinoma: Old and Emerging Therapeutic Targets

Cancers, Journal Year: 2024, Volume and Issue: 16(5), P. 901 - 901

Published: Feb. 23, 2024

Liver cancer, predominantly hepatocellular carcinoma (HCC), globally ranks sixth in incidence and third cancer-related deaths. HCC risk factors include non-viral hepatitis, alcohol abuse, environmental exposures, genetic factors. No specific alterations are unequivocally linked to tumorigenesis. Current standard therapies surgical options, systemic chemotherapy, kinase inhibitors, like sorafenib regorafenib. Immunotherapy, targeting immune checkpoints, represents a promising avenue. FDA-approved checkpoint such as atezolizumab pembrolizumab, show efficacy, combination enhance clinical responses. Despite this, the treatment of (HCC) remains challenge, complex tumor ecosystem immunosuppressive microenvironment associated with it hamper efficacy available therapeutic approaches. This review explores current advanced approaches treat HCC, considering both known new potential targets, especially derived from proteomic analysis, which is today considered most approach. Exploring novel strategies, this discusses antibody drug conjugates (ADCs), chimeric antigen receptor T-cell therapy (CAR-T), engineered antibodies. It then reports systematic analysis main ligand/receptor pairs molecular pathways reported be overexpressed cells, highlighting their limitations. Finally, TGFβ, one targets microenvironment.

Language: Английский

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Hepatocellular carcinoma: signaling pathways and therapeutic advances

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: Feb. 6, 2025

Abstract Liver cancer represents a major global health concern, with projections indicating that the number of new cases could surpass 1 million annually by 2025. Hepatocellular carcinoma (HCC) constitutes around 90% liver and is primarily linked to factors incluidng aflatoxin, hepatitis B (HBV) C (HCV), metabolic disorders. There are no obvious symptoms in early stage HCC, which often leads delays diagnosis. Therefore, HCC patients usually present tumors advanced incurable stages. Several signaling pathways dis-regulated cause uncontrolled cell propagation, metastasis, recurrence HCC. Beyond frequently altered therapeutically targeted receptor tyrosine kinase (RTK) involved differentiation, telomere regulation, epigenetic modification stress response also provide therapeutic potential. Investigating key their inhibitors pivotal for achieving advancements management At present, primary approaches (TKI), immune checkpoint (ICI), combination regimens. New trials investigating therapies involving ICIs TKIs or anti-VEGF (endothelial growth factor) therapies, as well combinations two immunotherapy The outcomes these expected revolutionize across all Here, we here comprehensive review cellular pathways, potential, evidence derived from late-stage clinical discuss concepts underlying earlier trials, biomarker identification, development more effective therapeutics

Language: Английский

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Estimation of TP53 mutations for endometrial cancer based on diffusion-weighted imaging deep learning and radiomics features

BMC Cancer, Journal Year: 2025, Volume and Issue: 25(1)

Published: Jan. 9, 2025

To construct a prediction model based on deep learning (DL) and radiomics features of diffusion weighted imaging (DWI), clinical variables for evaluating TP53 mutations in endometrial cancer (EC). DWI data from 155 EC patients were included this study, consisting 80 the training set, 35 test 40 external validation set. Radiomics features, convolutional neural network-based DL analyzed. Feature selection was performed using Mann-Whitney U test, LASSO regression, SelectKBest. Prediction models established by gaussian process (GP) decision tree (DT) algorithms evaluated area under receiver operating characteristic curve (AUC), net reclassification index (NRI), calibration curves, analysis (DCA). Compared to (AUCtraining = 0.830, AUCtest 0.779, AUCvalidation 0.711), 0.810, 0.710, 0.839), 0.780, 0.685, 0.695) models, combined GP algorithm, which consisted four five two variables, not only demonstrated highest diagnostic efficacy 0.949, 0.877, 0.914) but also led an improvement risk mutation (NIRtraining 66.38%, 56.98%, 83.48%, NIRtest 50.72%, 80.43%, 89.49%, NIRvalidation 64.58%, 87.50%, 120.83%, respectively). In addition, exhibited good agreement utility curves DCA analyses, respectively. A algorithm as well can effectively assess EC.

Language: Английский

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Cow placenta extract ameliorates d-galactose-induced liver damage by regulating BAX/CASP3 and p53/p21/p16 pathways

Journal of Ethnopharmacology, Journal Year: 2024, Volume and Issue: 323, P. 117685 - 117685

Published: Jan. 1, 2024

Placenta is a kind of traditional Chinese medicine, known as "Ziheche", which has the function tonifying qi and blood, nourishing liver kidney. extract (PE) been used for delaying organismal aging treating various diseases. Cow placenta rich natural resource with large mass. Its composition similar to that human placenta, but it not effectively utilized. However, little about effect CPE on mice.

Language: Английский

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Genomics of adaptive evolution in the woolly mammoth

Current Biology, Journal Year: 2023, Volume and Issue: 33(9), P. 1753 - 1764.e4

Published: April 7, 2023

Ancient genomes provide a tool to investigate the genetic basis of adaptations in extinct organisms. However, identification species-specific fixed variants requires analysis from multiple individuals. Moreover, long-term scale adaptive evolution coupled with short-term nature traditional time series data has made it difficult assess when different evolved. Here, we analyze 23 woolly mammoth genomes, including one oldest known specimens at 700,000 years old, identify derived non-synonymous mutations unique species and obtain estimates these We find that its origin, had already acquired broad spectrum positively selected genes, ones associated hair skin development, fat storage metabolism, immune system function. Our results also suggest phenotypes continued evolve during last years, but through positive selection on sets genes. Finally, additional genes underwent comparatively recent selection, related skeletal morphology body size, as well gene may have contributed small ear size Late Quaternary mammoths.

Language: Английский

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TP53 mutations and MDM2 polymorphisms in breast and ovarian cancers: amelioration by drugs and natural compounds

Clinical & Translational Oncology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 11, 2025

Language: Английский

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Competitive signaling and cellular communications in myocardial infarction response

Molecular Biology Reports, Journal Year: 2025, Volume and Issue: 52(1)

Published: Jan. 16, 2025

Cell communication and competition pathways are malleable to Myocardial Infarction (MI). Key signals, transcriptive regulators, metabolites associated with apoptotic responses such as Myc, mTOR, p53 important players in the myocardium. The individual state of cardiomyocytes, fibroblasts, macrophages heart tissue adaptable times stress. overlapping Wnt/β-catenin, Notch, c-Kit exhibit involvement factors cell Depending on effects these genetic expression signal amplification, proliferative capacities previously stated cells that make up myocardium, amplify or diminish. This creates a distinct classification "fit" "unfit" cells. Beyond straightforward traits, intricate metabolite interactions between neighboring unveil complex battle. Strategic manipulation holds translational promise for rapid cardiac recovery post-trauma.

Language: Английский

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Clinical significance of TP53 alterations in advanced NSCLC patients treated with EGFR, ALK and ROS1 tyrosine kinase inhibitors: An update

Tumor Biology, Journal Year: 2023, Volume and Issue: 46(s1), P. S309 - S325

Published: Oct. 12, 2023

The development of targeted therapies for non-small cell lung cancer (NSCLC), such as the epidermal growth factor receptor ( EGFR), anaplastic lymphoma tyrosine kinase ALK), and ROS proto-oncogene 1 ROS1), has improved patients’ prognosis significantly extended progression-free survival. However, it remains unclear why some patients do not benefit from treatment much or have a rapid disease progression. It is considered that, apart oncogenic driver gene, molecular alterations in number caretaker gatekeeper genes impact efficacy therapies. tumor protein 53 TP53) gene one most frequently mutated NSCLC. To date, numerous studies investigated influence various TP53 on patient responsiveness to targeting EGFR, ALK, ROS1. This review focuses latest data concerning role prognostic and/or predictive biomarkers ROS1 inhibitors (TKIs) advanced NSCLC patients. Since presence mutations been linked its decreased therapy referenced studies, also discusses resistance. seems plausible that assessing mutation status could aid stratification optimal clinical decision-making. drawing meaningful conclusions about value co-mutations EGFR-, ALK- ROS1-positive hampered mainly by an insufficient knowledge regarding functional consequences alterations. integration next-generation sequencing into routine diagnostics will facilitate detection identification targetable genetic along with co-occurring variants. advancement holds potential accelerate understanding biological p53

Language: Английский

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Phenotypic heterogeneity in human genetic diseases: ultrasensitivity-mediated threshold effects as a unifying molecular mechanism

Journal of Biomedical Science, Journal Year: 2023, Volume and Issue: 30(1)

Published: July 31, 2023

Abstract Phenotypic heterogeneity is very common in genetic systems and human diseases has important consequences for disease diagnosis treatment. In addition to the many non-genetic (e.g., epigenetic, environmental) factors reported account part of heterogeneity, we stress importance stochastic fluctuation regulatory network topology contributing phenotypic heterogeneity. We argue that a threshold effect unifying principle explain phenomenon; ultrasensitivity molecular mechanism this effect; discuss three conditions occur. suggest effects occur not only at cellular level, but also organ level. context-dependence its relationship pleiotropy edgetic mutations. Based on model, provide practical strategies study diseases. By understanding identifying critical factor, may manipulate weak spot gently nudge system from an ultrasensitive state stable non-disease state. Our analysis provides new insight into prevention treatment

Language: Английский

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