Translational Insights into Molecular Mechanisms of Chemical Hepatocarcinogenesis for Improved Human Risk Assessment

Advances in Clinical Toxicology, Год журнала: 2024, Номер 9(1), С. 1 - 8

Опубликована: Янв. 1, 2024

Background: Hepatocellular carcinoma (HCC) is a prevalent liver cancer with major risk factors being hepatitis viral infections, alcohol, non-alcoholic fatty disease, and aflatoxin exposure. Both genotoxic non-genotoxic agents can induce HCC through mechanisms involving DNA damage, oxidative stress, chronic inflammation, disrupted signaling pathways like MAPK/ERK, PI3K/AKT, WNT/β-catenin PPARα. While rodent assays are utilized to detect potential chemical hepatocarcinogens, species differences in PPARα CAR/PXR activation impact human assessment. Purpose: This analysis provides an updated, critical examination of concordance hepatic carcinogenesis inform safety assessment tumor findings. Main Body: Rodent including 2-year bioassays, transgenic models, short-term studies tumors lifetime exposure or early biomarkers. However, rodent-specific activation, along hepatitis, highlight key interspecies differences. Determining mode action relevance requires evaluating mechanistic validity pivotal events leading across species. Non-genotoxic compounds eliciting activate PPARα, CAR/PXR, other triggering increased cell replication; but downstream may differ liver. Understanding applicability these humans as well incorporating into experimental models for accurate Conclusion: In summary, elucidating conserved versus divergent molecular between rodents essential appropriately interpreting findings safeguarding health science-based frameworks regulatory decision-making processes around hazards.

Язык: Английский

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Schisandra chinensis in Liver Disease: Exploring the Mechanisms and Therapeutic Promise of an Ancient Chinese Botanical

Archives of Pharmacology and Therapeutics, Год журнала: 2024, Номер 6(1), С. 27 - 33

Опубликована: Янв. 1, 2024

Background: Schisandra chinensis is a traditional Chinese herbal medicine that has been used for centuries liver health. The active lignans in Schisandra, including schisandrin and gomisins, have exhibited anti-inflammatory, antioxidant, hepatoprotective properties preliminary studies. With rising rates of chronic diseases globally, there interest the potential therapeutic role Schisandra. Purpose: To comprehensively review current evidence treating injury disease synthesize implications future human research. Main body: extracts decreased inflammatory cytokines oxidative stress markers increased endogenous antioxidant activity animal models, suggesting utility mitigating inflammation damage. Additional preclinical studies demonstrated attenuated enzyme levels, necrosis, fibrosis progression chemical-induced hepatotoxicity with treatment. Enhanced cytochrome P450 activity, glutathione production, glycogen synthesis were also observed, improving detoxification regeneration capacity. Small trials hepatitis nonalcoholic fatty showed improved enzymes symptoms supplementation but limited quality sample size. Conclusion: biologically relevant mechanisms warrant further research on its as phytotherapy. Well-designed, large-scale clinical are needed to establish efficacy safety applications.

Язык: Английский

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Transforming Screening, Risk Stratification, and Treatment Optimization in Chronic Liver Disease Through Data Science and translational Innovation

The Indonesian Journal of Gastroenterology Hepatology and Digestive Endoscopy, Год журнала: 2024, Номер 25(1), С. 53 - 62

Опубликована: Май 16, 2024

Background: Chronic liver diseases continue to face challenges in prognosis, treatment selection, disease mechanisms, screening, and therapeutic optimization. Promising innovations could address these gaps through data integration novel analytic approaches.Main Body: MAPS-CRAFITY integrating clinical variables, AFP, CT/MRI findings, transformer modeling of RFA improve HCC outcome prediction guide management. Analyses revealing IL21R as a PBC susceptibility gene implicating dysfunctional VWF processing portal hypertension deliver mechanistic insights. Quantifying childhood MAFLD informs screening needs, while supporting use G6PD deficient donors enables transplantation access expansion risk stratification. Updating Baveno criteria enhances an prognostic score identifies optimal candidates maximize efficacy.Conclusion: Recent research leverages diverse types, genetics, imaging, machine learning develop integrated predictive systems that allow more personalized therapy selection. Elucidating molecular pathways provides targets biomarkers. Evidence-based models facilitate delivering tailored interventions. Optimization current modalities validation patient selection improves real-world effectiveness. Multifaceted modern approaches promise unmet needs transform hepatology care.

Язык: Английский

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Type 1 diabetes mellitus: retrospect and prospect

Bulletin of the National Research Centre/Bulletin of the National Research Center, Год журнала: 2024, Номер 48(1)

Опубликована: Апрель 19, 2024

Abstract Background Type 1 diabetes (T1D) is an autoimmune disease leading to destruction of insulin-producing pancreatic beta cells. Both genetic and environmental factors contribute pathogenesis. The incidence T1D increasing worldwide, with significant geographic ethnic variations. Patients present symptoms hyperglycemia complications. Main body In T1D, autoreactive T cells autoantibodies destroy cells, causing insulin deficiency. Exogenous therapy essential but cannot replicate normal physiology. Management requires intensive lifestyle education on diet, exercise, glucose monitoring avoiding complications, in addition insulin. Novel therapies like immunotherapy, cell transplantation, artificial pancreas devices AI algorithms aim improve care. Strategies for reversing involve combination immunotherapies block autoimmunity regenerate via stem or xenotransplantation. Conclusion While type remains challenging, ongoing research provides hope. Elucidating individualized mechanisms translating findings into precision prevention treatment approaches are critical improving long-term outcomes. Innovative multi-targeted may fundamentally change the trajectory T1D.

Язык: Английский

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Realizing the Promise of Artificial Intelligence in Hepatocellular Carcinoma through Opportunities and Recommendations for Responsible Translation

Jurnal Online Informatika, Год журнала: 2024, Номер 9(1), С. 70 - 79

Опубликована: Апрель 26, 2024

This study aims to provide an overview of the current state-of-the-art applications artificial intelligence (AI) and machine learning in management hepatocellular carcinoma (HCC), explore future directions for continued progress this emerging field. is a comprehensive literature review that synthesizes recent findings advancements application AI techniques across various aspects HCC care, including screening early detection, diagnosis staging, prognostic modeling, treatment planning, interventional guidance, monitoring response. The draws upon wide range published research studies, focusing on integration with diverse data sources, such as medical imaging, clinical data, genomics, other multimodal information. results demonstrate AI-based systems have shown promise improving accuracy efficiency screening, diagnosis, tumor characterization compared traditional methods. Machine models integrating clinical, genomic outperformed conventional staging predicting survival recurrence risk. recommendation potential optimize personalized therapy selection, while augmented reality can guide procedures real-time. Moreover, longitudinal may enhance assessment response monitoring. Despite these promising findings, highlights need rigorous multicenter prospective validation standardized datasets, thoughtful consideration ethical implications before widespread implementation technologies management.

Язык: Английский

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Precision medicine for personalized cholecystitis care: integrating molecular diagnostics and biotherapeutics

Bulletin of the National Research Centre/Bulletin of the National Research Center, Год журнала: 2024, Номер 48(1)

Опубликована: Сен. 12, 2024

Abstract Background Acute cholecystitis, inflammation of the gallbladder, can lead to serious complications if not promptly diagnosed and managed. Conventional therapies have limitations, necessitating newer personalized approaches. Main body abstract This review examines recent advances transforming cholecystitis care. Diagnostically, molecular techniques like next-generation sequencing rapidly identify causative microbes from gallbladder specimens, enabling targeted antimicrobial therapy. Regarding treatment, phage therapy uses viruses lyse pathogenic bacteria. RNA interference CRISPR-Cas9 gene editing silence microbial virulence factors. Probiotics competitively exclude pathogens. Robotics fluorescence imaging refine surgical techniques. Additional emerging modalities include biosensors detecting inflammatory mediators, regenerative tissue engineering using stem cells, artificial intelligence for real-time decision support. However, optimal integration novel technologies with current best practices remains unknown. Further research is needed validate optimize diagnostics therapeutics cholecystitis. Short conclusions Advances in sequencing, CRISPR editing, robotics, other biotechnologies promise transform precision management when thoughtfully implemented. controlled trials are still required define conventional supportive care antibiotics.

Язык: Английский

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Artemisinin and its derivatives throughout the therapeutic mechanisms and clinical potential

Discover Chemistry., Год журнала: 2025, Номер 2(1)

Опубликована: Фев. 10, 2025

Язык: Английский

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Epigenetic factors in posttraumatic stress disorder resilience and susceptibility

Egyptian Journal of Medical Human Genetics, Год журнала: 2025, Номер 26(1)

Опубликована: Март 20, 2025

Abstract Background Posttraumatic stress disorder (PTSD) affects approximately 8% of the US population, with varying susceptibility among individuals exposed to trauma. While genetic factors contribute PTSD risk, emerging evidence suggests that epigenetic mechanisms play a crucial role in translating environmental exposures into lasting neurobiological changes. Purpose This review provides comprehensive analysis cutting-edge research on PTSD, particular emphasis novel findings regarding resilience and mechanisms. We explore recent technological advances their applications understanding pathophysiology. Main body Advanced epigenomic approaches have revealed complex interactions between DNA methylation, histone modifications, non-coding RNAs PTSD. Novel highlight cell type-specific signatures temporal dynamics following trauma exposure. Single-cell studies identified previously unknown cellular heterogeneity responses. Recent data modifications not only influence individual but may also transgenerational transmission effects. Integrative multi-omics new insights molecular networks underlying vulnerability. Conclusion unprecedented complexity These open avenues for personalized interventions based profiles suggest therapeutic strategies targeting modifications. enhanced has significant implications risk assessment, prevention, treatment. Graphical abstract

Язык: Английский

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Liver stiffness as a dynamic predictor of decompensation and mortality in alcohol-related liver disease

Deleted Journal, Год журнала: 2024, Номер 1(1)

Опубликована: Ноя. 5, 2024

Alcohol-related liver disease (ALD) is a significant global health concern, contributing substantially to liver-related morbidity and mortality. Liver stiffness measurement (LSM) has emerged as non-invasive, reliable method for assessing fibrosis cirrhosis in ALD. This review examines the role of LSM predicting monitoring risk decompensation mortality ALD patients. We conducted comprehensive analysis recent literature on techniques, including transient elastography, magnetic resonance acoustic radiation force impulse imaging, shear wave elastography. The focused pathophysiology ALD, predictive value hepatic mortality, its use progression treatment response. demonstrates strong power with values above 20–25 kPa generally associated increased risk. Serial measurements provide valuable insights into effects alcohol abstinence or relapse. Integration other biomarkers prognostic models enhances stratification clinical decision-making. However, challenges remain standardizing techniques establishing ALD-specific cutoff values. represents advance management, offering dynamic repeatable measure health. Its ability predict outcomes monitor response makes it tool guiding care. Future research should focus standardization, multimodal approaches combining biomarkers, application artificial intelligence data further improve utility management.

Язык: Английский

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Polyploidy-mediated resilience in hepatic aging: molecular mechanisms and functional implication

Egyptian Liver Journal, Год журнала: 2024, Номер 14(1)

Опубликована: Ноя. 12, 2024

Abstract Background Polyploidization, a process where cells acquire additional chromosome sets, is unique characteristic of hepatocytes. This has been increasingly recognized as an adaptive mechanism for maintaining liver function during aging, period characterized by cellular senescence, DNA damage, and metabolic dysregulation. Purpose review explores the molecular mechanisms underlying hepatocyte polyploidization its potential role in promoting resilience against aging-related decline function. We assess how polyploid hepatocytes contribute to genomic stability, stress resistance, adaptation, highlighting their relevance aging. Main body Hepatocyte occurs through such cytokinesis failure endoreplication, leading binuclear or mononuclear cells. Polyploid exhibit enhanced repair capacity, which helps mitigate accumulation age-related damage. The increased gene dosage facilitates better responses, particularly oxidative genotoxic insults. Metabolic adaptations, including xenobiotic metabolism lipid regulation, further support liver’s ability maintain homeostasis Additionally, demonstrate altered epigenetic landscapes proteostasis mechanisms, contributing improved reduced susceptibility senescence. These adaptations collectively enhance structural challenges. Conclusion represents critical protective that safeguard instability, dysfunction, stress. Understanding pathways driving could pave way novel therapeutic strategies combat disorders health span. Graphical

Язык: Английский

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