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Original Article Open Access
DysUFMylation of SREBP1 Promotes the Progression of Hepatocellular Carcinoma by Reprogramming Lipid Metabolism
Xukang Gao, Zeping Han, Min Xu, Zhutao Wang, Guoqiang Sun, Hao Xiao, Dai Zhang, Shuangjian Qiu, Ning Ren, Chenhao Zhou, Yong Yi
Published online October 22, 2025
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2025.00318
Abstract
Sterol regulatory element-binding protein 1 (SREBP1), a key regulator of lipogenesis, is highly expressed in tumors, but the mechanisms sustaining its elevated levels remain unclear. [...] Read more.

Sterol regulatory element-binding protein 1 (SREBP1), a key regulator of lipogenesis, is highly expressed in tumors, but the mechanisms sustaining its elevated levels remain unclear. The role of UFMylation, a posttranslational modification, in modulating SREBP1 stability and tumor progression has not been explored. This study aimed to investigate the role of UFMylation in the progression of liver cancer.

Liquid chromatography-tandem mass spectrometry was employed to investigate the interacting proteins of ubiquitin-fold modifier 1-specific ligase 1 (UFL1). Knockdown of UFL1 and DDRGK domain-containing protein 1 (DDRGK1) was performed to assess SREBP1 stability. In vitro and in vivo models of hepatocellular carcinoma (HCC) were used to evaluate tumor progression. Clinical correlations between UFL1/DDRGK1 and SREBP1 levels were analyzed in HCC patient samples.

SREBP1 undergoes UFMylation, which synergizes with ubiquitination to reduce its stability. Depletion of UFL1 or DDRGK1 increased SREBP1 stability, driving HCC progression. Clinically, UFL1 and DDRGK1 levels were reduced in HCC tissues and inversely correlated with SREBP1 expression. Fatostatin (an SREBP1 inhibitor) enhanced the therapeutic effect of Lenvatinib in HCC models with low UFL1 expression.

UFMylation is a critical posttranslational modification that destabilizes SREBP1, and its dysregulation contributes to HCC progression. Targeting the UFMylation-SREBP1 axis, particularly through Fatostatin and Lenvatinib combination therapy, represents a novel therapeutic strategy for HCC.

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Review Article Open Access
Tumor Vaccines in Hepatocellular Carcinoma: Advances, Challenges, and the Path Toward Precision Immunotherapy
Bin Niu, Jun Xu, Liaoyun Zhang
Published online January 19, 2026
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2025.00401
Abstract
Primary hepatocellular carcinoma (HCC) remains one of the leading causes of cancer-related mortality worldwide, with curative options still limited for patients with advanced disease. [...] Read more.

Primary hepatocellular carcinoma (HCC) remains one of the leading causes of cancer-related mortality worldwide, with curative options still limited for patients with advanced disease. As an emerging modality of cancer immunotherapy, tumor vaccines represent a promising approach that activates the host immune system to recognize and eliminate malignant cells. Multiple vaccine platforms, including peptide vaccines, dendritic-cell vaccines, nucleic-acid vaccines, and viral-vector vaccines, have been explored for HCC. Among these, peptide- and dendritic-cell-based vaccines are supported by the most extensive clinical data, demonstrating favorable safety and immunogenicity profiles. The advent of personalized therapeutic cancer vaccines based on tumor-specific antigens has further refined the precision of vaccine design. Nevertheless, several major challenges persist, including immune suppression within the tumor immune microenvironment, marked tumor heterogeneity, immune-escape mechanisms, and limited vaccine immunogenicity, all of which hinder clinical efficacy. In addition, issues related to standardization, large-scale production, and regulatory oversight remain unresolved. Recent advances in sequencing technology, nanotechnology, and artificial intelligence have opened new avenues for optimizing vaccine platforms and delivery strategies. Combination therapies that integrate cancer vaccines with immune checkpoint inhibitors, chemotherapy, or locoregional treatments are also being actively investigated to improve patient outcomes. In summary, although vaccine-based immunotherapy for HCC is still at an early stage, its integration with personalized medicine and multimodal therapeutic strategies holds great potential for improving the long-term prognosis of patients with HCC. Therefore, this review aims to systematically summarize current advances in tumor vaccine–based immunotherapy for hepatocellular carcinoma, with a particular focus on vaccine platforms, target antigens, clinical trial outcomes, and future challenges for clinical translation.

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Review Article Open Access
The Oncodarwinian Hypothesis: Cancer as a Potential Immunoadaptive Response and Artificial Intelligence-based 3D Printed p53 Superproteins
Antonio Araújo
Published online January 22, 2026
Exploratory Research and Hypothesis in Medicine. doi:10.14218/ERHM.2025.00041
Abstract
This review presents the Oncodarwinian Hypothesis, which proposes a new medical paradigm: that of cancer as a potential macro-immunoadaptive response (susceptible to fine-tuning [...] Read more.

This review presents the Oncodarwinian Hypothesis, which proposes a new medical paradigm: that of cancer as a potential macro-immunoadaptive response (susceptible to fine-tuning or reprogramming/management via artificial intelligence-based 3D printed p53 superproteins). A traditional hypothesis-generation method was adopted; it entails observing a biophenomenon longitudinally (tumor-precursor out-of-control cell division), formulating and refining targeted research questions, and then, rooted in a prior interdisciplinary theoretical framework, outlining (per deductive reasoning) a testable answer or statement apt to predict outcomes. Two main theoretical findings emerge from this review: the plausibility of a wireless p53 superprotein molecular biochip (3D printed) and cancer cells’ dual-focus immunological nature. It will be necessary to approach the key issue and prognosis of (supposedly meaningless) uncontrolled cell division in a different light. Basically, the same diseasing cancer also constitutes a self-replicating immunoadaptive algorithm that needs to be deciphered. An interdisciplinary quest to unravel its “source code” involves genomic palaeontology and learning the natural selection programming language — for developing (personalized) artificial intelligence-assisted p53 superproteins.

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Review Article Open Access
Emerging Roles of Hepatocellular Carcinoma Gene Signatures in Prognosis and Immunotherapy: Challenges and Opportunities
Amany Wahb, Ghada A. Abdel-Aleem, Noha O. Shawky, Mohamed El-Kassas
Published online April 23, 2026
Gene Expression. doi:10.14218/GE.2025.00073
Abstract
Hepatocellular carcinoma (HCC) remains one of the most fatal cancers, primarily due to late diagnosis and the lack of effective early biomarkers. Recent advances in multi-omics [...] Read more.

Hepatocellular carcinoma (HCC) remains one of the most fatal cancers, primarily due to late diagnosis and the lack of effective early biomarkers. Recent advances in multi-omics and liquid biopsy technologies hold promise for improving early detection, prognostication, and monitoring of HCC. Understanding the immune landscape of HCC through genetic and epigenetic signatures is essential for identifying therapeutic targets and improving immunotherapy outcomes. This review aims to present current findings on immune-related biomarkers, multi-omics strategies, and biomarker validation in HCC. It also aims to evaluate the role of liquid biopsy and gene signatures in predicting treatment responses, with a specific focus on their applications in immunotherapy. The goal is to provide a comprehensive framework for integrating these emerging tools into clinical practice. The integration of multi-omics approaches has led to the identification of robust gene signatures that predict HCC prognosis and response to immune checkpoint inhibitors. Liquid biopsy technologies, including circulating tumor DNA, provide non-invasive alternatives for monitoring tumor evolution and therapeutic responses. Despite promising results, challenges remain in clinical validation, particularly in cross-platform reproducibility and the interpretation of complex multi-omics data. While genetic biomarkers are rapidly advancing, their clinical application in personalized medicine remains hindered by technical and ethical challenges, such as data privacy, informed consent, and method standardization. The integration of multi-omics data and liquid biopsies offers a promising path toward real-time, personalized treatment and the development of universal prognostic signatures for HCC. However, successful clinical adoption depends on cross-disciplinary collaboration to standardize data protocols and overcome challenges regarding accuracy, reproducibility, and patient privacy.

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Original Article Open Access
Gene–environment Interaction of GWAS Loci and Reproductive History in Uterine Fibroid Risk: A Case-control Study
Liubov Ponomareva, Ekaterina Barysheva, Anna Dorofeeva, Ksenia Kobzeva, Olga Bushueva
Published online October 14, 2025
Gene Expression. doi:10.14218/GE.2025.00056
Abstract
Uterine fibroids (UFs) are common hormone-dependent tumors with a complex etiology involving both genetic and environmental factors. This study aimed to investigate, for the first [...] Read more.

Uterine fibroids (UFs) are common hormone-dependent tumors with a complex etiology involving both genetic and environmental factors. This study aimed to investigate, for the first time, the associations between loci from genome-wide association studies (GWAS) and environmental risk factors in UF development, with a particular focus on gene–environment interactions.

DNA samples from 737 women with UF and 451 healthy controls were genotyped for ten UF-associated GWAS single nucleotide polymorphisms (SNPs) using probe-based polymerase chain reaction in this case-control study.

SNP rs66998222 (LOC102723323, G/A) was associated with decreased UF risk in the total sample (odds ratio (OR) = 0.81, p = 0.038) and in patients with a history of induced abortion (OR = 0.70, p = 0.009). SNP rs11031731 (THEM7P, WT1, G/A) increased UF risk overall (OR = 1.39, p = 0.01), and in women with abortion history (OR = 1.60, p = 0.008) or without pelvic inflammatory disease (OR = 1.43, p = 0.02). SNPs rs641760 (PITPNM2, C/T) and rs2553772 (LOC105376626, G/T) showed protective effects depending on abortion history. SNP rs1986649 (FOXO1, C/T) was associated with later UF onset (p = 0.049) and slower growth (p = 0.017). GWAS loci influence UF-related genes involved in proliferation, inflammation, and hormone metabolism, underscoring their pathogenic role.

Induced abortions and inflammation modify the effects of GWAS-identified UF risk loci, with allele-specific impacts on hormonal, inflammatory, and repair pathways. Replication in diverse cohorts is needed to validate these population-specific effects.

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Hot Topic Commentary Open Access
Dengue Viral Infection and Associated Liver Disease
Moana Da Silva Santiago, George Y. Wu
Published online March 2, 2026
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2025.00566
Review Article Open Access
Bridging Traditional Medicine with Modern Technology: “Omics”-guided Herbal Pharmacovigilance for Integrative Liver Health
Anuradha Singh
Published online March 28, 2026
Future Integrative Medicine. doi:10.14218/FIM.2025.00059
Abstract
This review aims to advocate for a paradigm shift in herbal safety by proposing a cohesive molecular framework that integrates advanced “omics” technologies with artificial intelligence [...] Read more.

This review aims to advocate for a paradigm shift in herbal safety by proposing a cohesive molecular framework that integrates advanced “omics” technologies with artificial intelligence (AI) to address the clinical challenges of herb-induced liver injury (HILI). Traditional herbal medicine constitutes a substantial, yet often unregulated, component of global healthcare, driving high patient exposure alongside a significant and escalating clinical burden of HILI. Current pharmacovigilance systems are critically undermined by fundamental deficits, including severe underreporting, unknown population denominators, and pervasive product quality failures. Furthermore, the complexity of multi-ingredient formulations and the frequency of herb-drug interactions complicate causality assessment, particularly for high-risk drugs. To bridge the gap between empirical practice and contemporary safety standards, this integrated “omics”-AI paradigm transforms herbal safety from a reactive, population-level assessment into an evidence-based, personalized system. By enabling precise risk mitigation, this approach establishes a scientifically rigorous foundation for the future of integrative liver health. In conclusion, the synergy of molecular profiling and computational intelligence provides the necessary tools to modernize herbal pharmacovigilance, ensuring that traditional wisdom is effectively harmonized with modern technological standards for enhanced patient safety.

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Systematic Review Open Access
A Comparison of the Efficacy of Non-chemical versus Chemical Cleansers against Candida Species on Removable Dental Prostheses: A Systematic Review
Mohammed Waleed Nazer, Abdullah Zamil Alzuwaihri, Belal Ammar Alakkad, Majed Ahmed Alamoudi, Mohammed Hasen Alqurashi, Ahmad Mohammad Gharib, Manar Hamed Almehyawi, Mohammed Shammas
Published online January 23, 2026
Journal of Exploratory Research in Pharmacology. doi:10.14218/JERP.2025.00041
Abstract
Candida species, particularly Candida albicans, are major contributors to denture-induced stomatitis because of their ability to form biofilms on removable dental prostheses. Although [...] Read more.

Candida species, particularly Candida albicans, are major contributors to denture-induced stomatitis because of their ability to form biofilms on removable dental prostheses. Although chemical cleansers are effective, concerns regarding material degradation and mucosal irritation have spurred interest in non-chemical alternatives. This review aims to systematically compare the efficacy of chemical and non-chemical denture cleansers in reducing Candida spp. on removable dental prostheses.

A systematic review was conducted according to the PRISMA 2020 guidelines. Comprehensive searches of PubMed, Scopus, and Web of Science (2003–2025) yielded 624 records. After duplicate removal and screening, 20 studies (10 randomized controlled trials (RCTs) and 10 in vitro studies) were included. The risk of bias was assessed using the Cochrane Risk of Bias 2.0 for RCTs and QUIN/SYRCLE tools for in vitro studies.

Chemical cleansers such as sodium hypochlorite (0.25–2.5%), chlorhexidine (0.2–2%), and effervescent peroxide tablets achieved 80–100% colony-forming unit reduction in most studies, with some reporting complete biofilm eradication. In contrast, non-chemical agents showed a 40–85% colony-forming unit reduction rate. Chemical cleansers caused increased surface roughness and discoloration in six of the ten studies included. Non-chemical agents preserved material integrity and were preferred by patients for their taste and ease of use. The risk of bias was low to moderate in 80% of the RCTs and low in 10 of the 13 in vitro studies.

Chemical denture cleansers are more potent antifungal agents, but they may damage prosthetic materials. Non-chemical cleansers offer safe and moderately effective alternatives to chemical cleansers. A personalized, evidence-based oral hygiene regimen is recommended for patients.

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Review Article Open Access
Artificial Intelligence in Genitourinary Pathology: A Translational Readiness Map
Ankush U. Patel, Amanda Dy, Anil V. Parwani, Swati Satturwar
Published online March 13, 2026
Journal of Clinical and Translational Pathology. doi:10.14218/JCTP.2025.00056
Abstract
Artificial intelligence (AI) translation in genitourinary (GU) pathology has progressed unevenly across organs and tasks. This review addresses a central clinical question: which [...] Read more.

Artificial intelligence (AI) translation in genitourinary (GU) pathology has progressed unevenly across organs and tasks. This review addresses a central clinical question: which GU pathology AI applications are deployment-ready, which require further validation, and what frameworks can guide safe implementation? We synthesize evidence across GU organs and introduce pragmatic translation frameworks to guide deployment and prioritize translational research.

Narrative review integrating foundational literature with targeted 2023–2025 publications, emphasizing regulatory milestones, external validation, and prospective studies. Literature was identified through PubMed, Embase, and conference proceedings using structured search terms for AI, digital pathology, and GU organ-specific queries. For each organ/task, we mapped evidence strength, regulatory maturity, generalizability, workflow integration, safety, and feasibility to a Translational Readiness Index (TRI) rubric (0–30 scale).

Prostate biopsy AI demonstrates the strongest maturity (TRI 26/30), supported by U.S. Food and Drug Administration-cleared systems, multi-site validation, and prospective implementations showing efficiency gains and reduced ancillary testing. Bladder cytology shows moderate readiness (TRI 19/30), with commercial offerings supporting pilotable prescreening workflows aligned with the Paris System when paired with uncertainty-aware deferral. Bladder histology, renal neoplasia, and low-prevalence domains (testis, penis) remain emerging (TRI 6–15/30), constrained by label variability, rare subtype underrepresentation, and limited external validation.

The TRI rubric, SURE-Path safety bundle, and VALIDATED/ORCHESTRATE implementation pathway provide a practical template for evidence-based deployment in GU pathology. Clinically defensible translation requires matching intended use to validation evidence, with explicit safeguards for emerging applications.

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Review Article Open Access
Curcumin as a Chemotherapy Compound for Treatment of Breast Cancer: A Review
Mohammad Reza Kasaai
Published online January 30, 2026
Cancer Screening and Prevention. doi:10.14218/CSP.2025.00022
Abstract
Breast cancer (BCA) is one of the most common cancers worldwide, with a high rate of incidence and mortality. This review provides global information on BCA therapy using curcumin. [...] Read more.

Breast cancer (BCA) is one of the most common cancers worldwide, with a high rate of incidence and mortality. This review provides global information on BCA therapy using curcumin. Chemotherapy, as an effective treatment for different stages of BCA, and curcumin, generally regarded as safe compound and an alternative to synthetic drugs, have been described for the treatment of BCA. A few parameters, including nano-curcumin versus bulk curcumin and its encapsulated form versus its corresponding free form, have been discussed. Curcumin, a safe and edible compound with antitumor properties, is a promising medicinal compound for the treatment of BCA. Encapsulation of curcumin enhances its stability and anticancer efficiency. Nano-curcumin exhibits superior properties when compared to its bulk counterparts, leading to notable interactions and effects.

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