Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 3 complete abstracts (667 words), 9 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
A compound formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids.
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: Carbamide; Carmol; Basodexan.
Where it fits in the MeSH classification
Research landscape
PubMed indexes 133,774 records tagged with the MeSH heading “Urea” (counts retrieved 2026-10-31). 18,261 of them (13.7%) were published from 2020 onward, and the busiest period so far is through 1999 with 63,751 records.
Reviews account for 7,444 records (5.6%) and meta-analyses for 614. Randomized controlled trials number 4,427 (3.3%) as a share of all records on the topic.
Show the data
| Period | Records |
|---|---|
| through 1999 | 63,751 |
| 2000-2009 | 22,627 |
| 2010-2019 | 29,135 |
| 2020 onward | 18,261 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 7,444 | 5.6% |
| Meta-analyses | 614 | 0.5% |
| Randomized controlled trials | 4,427 | 3.3% |
Method: PubMed query "Urea"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-31.
Reading the evidence in drugs and chemicals
Studies of a chemical or drug can answer very different questions: what it is and how it behaves in cells and animals, how the body handles it, and whether it changes outcomes in people. Laboratory and animal findings often do not carry over to patients, and observational studies of exposures are confounded by who uses a substance and why. Nothing on this page is a recommendation to use, avoid, start or stop any substance or medicine; talk to a qualified clinician or pharmacist about your own situation. Check the dose, the species, the comparison group and whether a patient-relevant outcome was measured.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
| Study / authors | Year | Source label / design | Europe PMC citations | Licence / source |
|---|---|---|---|---|
| AARS1-mediated AKR1B10 lactylation stabilizes an aerobic glycolysis-positive feedback loop to drive lenvatinib resistance in hepatocellular carcinoma | 2026 | Research article Design not recorded in structured metadata | 12 | cc by PMID 41454479 · DOI · PMC12743142 |
| Lenvatinib plus transarterial chemoembolization and PD-1 inhibitors as conversion therapies for unresectable intermediate-advanced hepatocellular carcinoma: a phase 2 trial and exploratory biomolecular study | 2026 | Research article Design not recorded in structured metadata | 10 | cc by PMID 41565617 · DOI · PMC12823698 |
| Self-Adaptive Allantoin@ZIF8 Nanocomposite Hydrogel with Resveratrol Synergy for MRSA-Infected Wound Regeneration | 2026 | Research article Design not recorded in structured metadata | 6 | cc by PMID 41837579 · DOI · PMC13073323 |
AARS1-mediated AKR1B10 lactylation stabilizes an aerobic glycolysis-positive feedback loop to drive lenvatinib resistance in hepatocellular carcinoma [1]
Abstract reading summary — source excerpts
- Opening excerpt
- BackgroundLenvatinib resistance (LR) represents a significant obstacle in hepatocellular carcinoma (HCC) treatment.
- Closing excerpt
- Targeting AKR1B10 with epalrestat synergizes with lenvatinib to overcome resistance in preclinical models.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (295 words)
BackgroundLenvatinib resistance (LR) represents a significant obstacle in hepatocellular carcinoma (HCC) treatment. Aldo-keto reductase family 1 member B10 (AKR1B10) is involved in tumour metabolic reprogramming; however, its role in LR remains unclear.MethodsBioinformatics analyses of public databases were integrated and validated in established LR HCC cell lines. Functional assays (CCK-8, flow cytometry and Seahorse XF analysis) were performed to assess proliferation, apoptosis and aerobic glycolysis. Post-translational modifications of AKR1B10 were characterized using co-immunoprecipitation, mass spectrometry and western blot.ResultsAKR1B10 was identified as a critical driver of resistance by establishing a metabolic positive feedback loop. Bioinformatics analyses and experimental validation demonstrated that AKR1B10 upregulation correlates with therapeutic resistance. Functional studies indicated that AKR1B10 promotes resistance by enhancing aerobic glycolysis. Mechanistically, alanyl-tRNA synthetase 1 mediates lactylation modification at AKR1B10 lysine 173 (K173), stabilizing AKR1B10 by blocking ubiquitin (Ub)-proteasomal degradation. Stabilized AKR1B10 interacts physically with lactate dehydrogenase A (LDHA), promoting LDHA phosphorylation at Y10 and accelerating glycolytic lactate production. The increased lactate subsequently induces histone H3K18 lactylation (H3K18la), which transcriptionally upregulates LDHA expression. Thus, a self-reinforcing AKR1B10-lactate-LDHA amplification circuit is formed. Clinical analyses confirmed elevated AKR1B10 expression in LR HCC patient tissues. Importantly, targeting this axis with the AKR1B10 inhibitor epalrestat (EPA) synergized with lenvatinib, overcoming resistance in xenograft mouse models and patient-derived xenograft models.ConclusionsThese findings establish AKR1B10 as both a biomarker and a therapeutic target in HCC. They reveal a novel lactylation-driven glycolytic adaptation mechanism and support the clinical translation of combined EPA-lenvatinib therapy.Key pointsAKR1B10 confers lenvatinib resistance by enhancing aerobic glycolysis in HCC cells. AKR1B10 undergoes AARS1-mediated lactylation at K173, stabilizing it by antagonizing ubiquitin-proteasomal degradation. AKR1B10 promotes LDHA Y10 phosphorylation, boosting lactate production, which drives H3K18la-mediated transcriptional upregulation of LDHA, creating a feed-forward loop. Targeting AKR1B10 with epalrestat synergizes with lenvatinib to overcome resistance in preclinical models.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 41454479 · DOI · PMC12743142
Lenvatinib plus transarterial chemoembolization and PD-1 inhibitors as conversion therapies for unresectable intermediate-advanced hepatocellular carcinoma: a phase 2 trial and exploratory biomolecular study [2]
Abstract reading summary — source excerpts
- Opening excerpt
- Conversion therapy remains an uncommon strategy for managing unresectable hepatocellular carcinoma (uHCC) due to limited evidence supporting its efficacy.
- Closing excerpt
- In summary, the LEN-TAP protocol demonstrates promising efficacy and acceptable tolerability as a conversion therapy in uHCC, with peripheral HLA-DR+CD38+CD8+ T cell abundance serving as a potential predictor of therapeutic benefit.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (173 words)
Conversion therapy remains an uncommon strategy for managing unresectable hepatocellular carcinoma (uHCC) due to limited evidence supporting its efficacy. To address this gap, we initiated a prospective phase 2 multicenter trial (NCT04997850) comparing the LEN-TAP regimen, combining lenvatinib, transarterial chemoembolization (TACE), and PD-1 inhibitors, against TACE alone in uHCC patients. The study's primary outcome was salvage liver resection (SLR) rate; secondary measures included objective response rate (ORR), overall survival (OS), event-free survival (EFS), recurrence-free survival (RFS), and safety profile. From October 2020 to November 2021, 142 eligible participants were assigned to LEN-TAP (n = 71) or TACE monotherapy (n = 71). At a median follow-up of 24.2 months, the LEN-TAP cohort exhibited a significantly higher SLR rate (59.2% vs. 18.3%, P +CD38+CD8+ T cells with improved treatment response. These T cells appear to mediate antitumor activity potentially through the CXCR6-PI3K-AKT signaling axis. In summary, the LEN-TAP protocol demonstrates promising efficacy and acceptable tolerability as a conversion therapy in uHCC, with peripheral HLA-DR+CD38+CD8+ T cell abundance serving as a potential predictor of therapeutic benefit.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 41565617 · DOI · PMC12823698
Self-Adaptive Allantoin@ZIF8 Nanocomposite Hydrogel with Resveratrol Synergy for MRSA-Infected Wound Regeneration [3]
Abstract reading summary — source excerpts
- Opening excerpt
- Infected wounds present a formidable challenge to healing due to their complex pathological microenvironment, whereas conventional dressings are often functionally limited and ill-suited to adapt to dynamic wound changes.
- Closing excerpt
- This work provides a novel design paradigm for the development of intelligent, multifunctional therapeutic materials for infected wound management, with significant translational potential for clinical application.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (199 words)
Infected wounds present a formidable challenge to healing due to their complex pathological microenvironment, whereas conventional dressings are often functionally limited and ill-suited to adapt to dynamic wound changes. In this study, based on allantoin-loaded ZIF8 nanoparticles (Alla@ZIF8) and methacrylated quaternary ammonium carboxymethyl chitosan/resveratrol composite hydrogels (RMQCC), we designed and developed an adaptive multifunctional hydrogel system (Alla@ZIF8-Gel). This nanocomposite hydrogel exhibited multiple intelligent features, including pH-responsiveness and morphological adaptability. The quaternary ammonium carboxymethyl chitosan imparted well biocompatibility and robust antimicrobial properties. Electrostatic interactions and hydrogen bonds endowed hydrogels with excellent injectability and self-healing capabilities. The ZIF8 nanoparticles enabled the intelligent, on-demand release of allantoin, thereby promoting tissue regeneration. Resveratrol conferred potent antioxidant, anti-inflammatory, and immunomodulatory effects. The Alla@ZIF8-Gel dynamically modulated drug release kinetics in response to the wound microenvironment, synergistically delivering antibacterial, antioxidant, anti-inflammatory, and tissue-regenerative functions. Both in vitro and in vivo experimental results demonstrated that this adaptive hydrogel markedly accelerated the healing of MRSA-infected wounds, suppressed bacterial proliferation, alleviated oxidative damage and inflammatory responses, and enhanced collagen deposition, re-epithelialization, and neovascularization. This work provides a novel design paradigm for the development of intelligent, multifunctional therapeutic materials for infected wound management, with significant translational potential for clinical application.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 41837579 · DOI · PMC13073323
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article Targeted therapy for hepatocellular carcinoma [4]
- Research article Glibenclamide, metformin, and insulin for the treatment of gestational diabetes: a systematic review and meta-analysis [5]
- Research article A systematic review and meta-analysis of hypoglycemia and cardiovascular events: a comparison of glyburide with other secretagogues and with insulin [6]
- Research article How did lomustine become standard of care in recurrent glioblastoma? [7]
- Research article Accuracy of urea breath test in Helicobacter pylori infection: meta-analysis [8]
- Research article Mortality risk among sulfonylureas: a systematic review and network meta-analysis [9]
References
- Liu Z, Yuan J, Su S, Han J, Zeng N, Ma Y, et al.. AARS1-mediated AKR1B10 lactylation stabilizes an aerobic glycolysis-positive feedback loop to drive lenvatinib resistance in hepatocellular carcinoma. . 2026. PMID 41454479 · DOI · PMC12743142
- Zhang X, Cai H, Peng W, Wang H, Wu J, Zhu X, et al.. Lenvatinib plus transarterial chemoembolization and PD-1 inhibitors as conversion therapies for unresectable intermediate-advanced hepatocellular carcinoma: a phase 2 trial and exploratory biomolecular study. . 2026. PMID 41565617 · DOI · PMC12823698
- Zhu Y, Liu D, Zhao M, Jian X, Peng E, Zhao X, et al.. Self-Adaptive Allantoin@ZIF8 Nanocomposite Hydrogel with Resveratrol Synergy for MRSA-Infected Wound Regeneration. . 2026. PMID 41837579 · DOI · PMC13073323
- Huang A, Yang XR, Chung WY, Dennison AR, Zhou J. Targeted therapy for hepatocellular carcinoma. Signal Transduct Target Ther. 2020. PMID 32782275 · DOI · PMC7419547
- Balsells M, García-Patterson A, Solà I, Roqué M, Gich I, Corcoy R. Glibenclamide, metformin, and insulin for the treatment of gestational diabetes: a systematic review and meta-analysis. BMJ. 2015. PMID 25609400 · DOI · PMC4301599
- Gangji AS, Cukierman T, Gerstein HC, Goldsmith CH, Clase CM. A systematic review and meta-analysis of hypoglycemia and cardiovascular events: a comparison of glyburide with other secretagogues and with insulin. Diabetes Care. 2007. PMID 17259518 · DOI
- Weller M, Le Rhun E. How did lomustine become standard of care in recurrent glioblastoma?. Cancer Treat Rev. 2020. PMID 32408220 · DOI
- Ferwana M, Abdulmajeed I, Alhajiahmed A, Madani W, Firwana B, Hasan R, et al.. Accuracy of urea breath test in Helicobacter pylori infection: meta-analysis. World J Gastroenterol. 2015. PMID 25632206 · DOI · PMC4306177
- Simpson SH, Lee J, Choi S, Vandermeer B, Abdelmoneim AS, Featherstone TR. Mortality risk among sulfonylureas: a systematic review and network meta-analysis. Lancet Diabetes Endocrinol. 2015. PMID 25466239 · DOI
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-10-31.
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Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.