With the development of obese adipose tissue (AT), adipocytes undergo pathological changes from inert energy storage to excessive and active endocrine organs associated with disease hazards. Methyltransferase 3 (METTL3) is an RNA methyltransferase with key roles in AT development, functional maintenance and metabolic homeostasis. Licoisoflavone A (LIC‑A) is a prenylated flavonoid compound derived from licorice, which has anti‑inflammatory, antihypertrophic and antiproliferative activities; however, whether it directly modulates METTL3 expression and affects AT function in obesity remains unknown. In the present study, molecular docking of compounds from the traditional Chinese medicine formula Fangji‑Huangqi Decoction against METTL3, identified 16 top‑ranked candidate molecules. Among these candidates, LIC‑A was identified as a potential upstream regulator of METTL3 and markedly increased METTL3 expression. The effects of TNF‑α and lipopolysaccharide treatments on the inhibition of adipogenesis were successfully recovered by LIC‑A treatment of the adipogenic 3T3‑L1 cells, via the regulation of adipogenic cytokines, as well as the expression of inflammatory factors. These protective effects were similarly abolished by METTL3 knockdown, suggesting that the role of LIC‑A relies on METTL3. Moreover, in vivo data demonstrated that the administration of LIC‑A could notably recover body weight lipid metabolism, insulin resistance and gluconeogenesis in mice with reduced adipose deposition, as well as abate systemic inflammation. The novelty of the present study lies in three aspects: i) LIC‑A was identified as a previously unrecognized upstream positive regulator of METTL3 expression; ii) LIC‑A was demonstrated to alleviate adipokine dysregulation and AT inflammation through a METTL3‑dependent mechanism; and iii) the first in vivo experimental evidence that LIC‑A can improve obesity‑related metabolic disorders by promoting METTL3‑mediated m6A methylation in AT was provided. To the best of our knowledge, this is the first study to link a natural isoflavone compound from licorice to METTL3‑mediated post‑transcriptional regulation in the context of AT dysfunction.
Cervical cancer (CCa) is a worldwide health concern, particularly in low‑ and middle‑income countries. Human papillomavirus infection is a key risk factor in the development of CCa. Noncoding RNAs (ncRNAs), including microRNAs (miRNAs), circular RNAs (circRNAs) and long ncRNAs (lncRNAs), are important regulators of cancer progression, including CCa, offering potential therapeutic targets. Compared with lncRNAs and miRNAs, circRNAs are the least studied ncRNAs. circRNAs, distinguished by a closed‑loop structure and resistance to exonucleases, serve diverse roles in cancer, functioning as miRNA sponges and regulating gene expression. circRNAs are produced primarily by back‑splicing and comprise both intronic and exonic sequences. Notably, circRNAs are key regulators of alternative splicing, as they are able to enhance the expression of splicing factors (SFs) by sequestering miRNAs. Despite their importance, the interactions between circRNAs and SFs in CCa remain to be elucidated. The present review highlights the interplay between circRNAs and SFs in CCa pathogenesis; it describes the influence of SFs on circRNA production, the regulatory feedback between circRNAs and SFs, and the potential implications of this interaction in CCa diagnostics and therapeutics. To conduct the present review a targeted literature search was conducted across PubMed, Scopus and Google Scholar using defined search terms to identify peer‑reviewed studies published between 2006 and 2024. The findings were synthesized to explore the mechanistic insights and translational implications of circRNA‑SF interactions in CCa.
Following the publication of the above article, the authors have contacted the Editorial Office to explain that certain of the western blots featured in Figs. 3A and B, and 6A and B, on p. 2248 and 2250 respectively were chosen incorrectly. Specifically, the data chosen for the CLEC4M blots in Fig. 3A and B, and the p‑JAK1 blots in Fig. 6A and the STAT3 blots in Fig. 6B, were presented incorrectly in these figures. However, the authors retained their original data, and have submitted corrected versions of Figs. 3 and 6, now showing the correct data for the CLEC4M blots in Fig. 3A and B, and the p‑JAK1 blots in Fig. 6A and the STAT3 blots in Fig. 6B. These figures are featured on the next page. Note that the errors made in compiling these figures did not affect the results or the main conclusions reported in the study. All the authors approve of the publication of this corrigendum, and are grateful to the Editor of Molecular Medicine Reports for allowing them the opportunity to publish this. The authors regret their oversight in allowing these errors to be included in the paper, and apologize to the readership for any inconvenience caused. [Molecular Medicine Reports 22: 2245‑2252, 2020; DOI: 10.3892/mmr.2020.11336].
The global burden of bone metabolic disorders necessitates a shift from generic exercise recommendations toward personalized prescription strategies. Exercise confers skeletal protection through mechanotransduction, yet the underlying molecular networks remain incompletely understood. Multi‑omics technologies, including transcriptomics, proteomics, metabolomics and single‑cell spatial approaches, have revolutionized the capacity to decode exercise‑mediated bone adaptation at the systems level. The present review synthesizes current single‑omics landscapes and integrative multi‑omics analyses that elucidate the core regulatory networks, mechanobiological coupling mechanisms and multiorgan crosstalk that are implicated in the bone response to mechanical loading. Translational applications across clinical scenarios such as osteoporosis, osteoarthritis and disuse bone loss are evaluated, and the technical, analytical and translational challenges limiting clinical implementation are addressed. Finally, the present review provides a framework for translating multi‑omics molecular signatures into personalized exercise prescriptions for optimized skeletal health.
Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that certain of the cell migration and invasion data featured in Fig. 2C, G, H, K, L and O on p. 565‑6 were strikingly similar to data which appeared in a handful of other articles written by different authors at different research institutes, one of which had already been published in Journal of Biological Research‑Thessaloniki during the year before this paper was submitted to Molecular Medicine Reports. Owing to the fact that the contentious data in the above article had already been published prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 17: 562‑570, 2018; DOI: 10.3892/mmr.2017.7886].
Preterm brain injury remains a leading cause of long‑term neurodevelopmental impairment despite advances in neonatal care. Oxidative stress (OS), arising from mitochondrial dysfunction, nicotinamide adenine dinucleotide phosphate oxidase activation and iron‑mediated Fenton reactions, selectively damages the developing brain because of immature antioxidant defenses and vulnerable oligodendrocyte progenitor cells. Critically, OS triggers enduring epigenetic modifications including DNA methylation alterations, histone acetylation changes and microRNA dysregulation, thereby translating acute perinatal insults into sustained changes in gene expression. The complex cellular interplay involving microglia, astrocytes and the neurovascular unit determines injury progression and repair capacity. Emerging neuroprotective strategies include antioxidant therapies, pathway‑targeted agents and cell‑based approaches, while artificial intelligence applications show promise for early risk stratification and personalized monitoring, although these tools remain under prospective validation. The present review synthesized current evidence on the pathological cascade from OS to epigenetic dysregulation in preterm brain injury, evaluated the latest advances in neuroprotective interventions and aimed to inform the development of precision‑based, developmentally timed interventions that address the multifactorial nature of preterm brain injury and improve long‑term neurodevelopmental outcomes.
Although apoptosis is regarded as an irreversible and terminal process, recent research has identified anastasis as a cellular mechanism that enables cell recovery even after the activation of executioner caspases. While important in supporting tissue homeostasis following mild or transient injury, anastasis presents significant challenges in oncology, as cancer cells may exploit this phenomenon to evade chemotherapy, subsequently acquiring aggressive traits such as genomic instability, stem‑like properties, and increased metastatic capacity. N‑acetyl‑5‑methoxytryptamine (melatonin), recognized for its antioxidant activity and role as a mitochondrial regulator, has been associated with several biological processes that overlap with pathways involved in anastasis, including mitochondrial bioenergetics, redox homeostasis, and DNA repair mechanisms. However, direct evidence supporting a role for melatonin in regulating anastasis remains limited. The present review consolidated current insights into the molecular regulation of anastasis, examining its biphasic transcriptional profile and oncogenic consequences, while exploring the mechanistic links between melatonin biology and pathways relevant to apoptotic recovery and evaluating the therapeutic prospects of melatonin in targeting anastasis as a strategy to mitigate tumor recurrence and improve clinical outcomes.
Intestinal metaplasia (IM) represents a key stage in the progression of gastric mucosal lesions to gastric cancer, marked by a complex molecular pathogenesis and a lack of effective interventional strategies. Autophagy, a key mechanism for maintaining cell homeostasis, is closely associated with the onset and progression of IM. The present review aimed to summarize the role of autophagy in IM by integrating its association with risk factors and pathogenic mechanisms. The present study evaluated the impact of autophagy on inflammation, immune responses and cellular fate determination during IM. The present study summarized potential autophagy‑mediated therapeutic agents for IM treatment and future research directions and existing limitations, aiming to provide novel insight for preventing and managing this premalignant condition.
Following the publication of the above article, a concerned author drew to the authors' attention that they had apparently used an inappropriate antibody in their study: In the Materials and methods section, the authors had reported the use of Abcam's recombinant antibody against plant homeodomain (PHD) finger protein 1 (a.k.a. PHF1; cat. no. ab184951) to probe for the unrelated protein, tau paired helical filaments (PHFs). The authors acknowledged that they had made a methodological error: They were intending to detect tau phosphorylation at Ser396/404, but mistakenly had used the antibody against PHD finger protein 1 (cat. no. ab184951; Abcam); as a result, the western blot results shown in Figs. 3 and 7 for protein PHF1 were invalid. This error went unnoticed since the two antibodies shared the same abbreviation (PHF1), and the banding patterns obtained with the incorrect antibody appeared similar in trend to what the authors had expected to have found, which unfortunately masked the mistake during their internal data review. The Editor instructed the authors to repeat the PHF1 western blot experiments using the correct PHF1 antibody (Tau‑pSer396/404; cat. no. 87061‑1‑RR; Proteintech Group, Inc.). The new experiments yielded reproducible and valid results, and the authors have replaced the original data relating to protein PHF1 in Figs. 3 and 7; the revised versions of these figures are shown on the next page. Note that these errors did not affect the results or the main conclusions reported in the study. All the authors approve of the publication of this corrigendum, and are grateful to the Editor of Molecular Medicine Reports for allowing them the opportunity to publish this. The authors regret their oversight in selecting the wrong antibody for these specific western blot experiments, and apologize to the readership for any inconvenience caused. [Molecular Medicine Reports 22: 445‑453, 2020; DOI: 10.3892/mmr.2020.11131].
Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that the expression of BAX protein in Jurkat T cells, as shown in the western blots in Fig. 6A on p. 3392, was unexpected, since Jurkat cells have been reported to be BAX‑null [see the paper "A genome‑wide survey of mutations in the Jurkat cell line" by Gioia et al, Vol. 19, article no. 334 (2018)]. Furthermore, upon performing an independent analysis of the data in this paper, it came to light that the control β‑actin western blots featured in Fig. 4A and flow cytometric data included in Fig. 5B were strikingly similar to data that had already been submitted for publication to other journals in other articles written by different authors at different research institutes, one of which has since been retracted. Owing to the fact that the contentious data in the above article had already been submitted for publication prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 20: 3388‑3394, 2019; DOI: 10.3892/mmr.2019.10573].
Immune checkpoint inhibitors (ICIs) have shown promise in cancer therapy by enhancing antitumor immune responses, but patient responses are variable, with some experiencing limited efficacy and others suffering from severe immune‑related adverse events (irAEs). Identifying predictive biomarkers for ICI efficacy and toxicity is required for optimizing patient selection and treatment outcomes. MicroRNAs (miRNAs), small non‑coding RNA molecules that regulate gene expression, have emerged as potential biomarkers due to their role in immune regulation and tumor biology. Studies have shown that miRNA profiles in tumor tissues and blood can predict ICI responses. Specific miRNAs, such as miR‑155, miR‑21 and miR‑146a, are associated with enhanced antitumor responses, whereas others, such as miR‑34a and miR‑200c, are linked to resistance by modulating immune evasion. Additionally, altered miRNA expression reflects immune activation or dysregulation, playing a role in irAEs. The present review discussed the potential of miRNAs as predictive biomarkers for ICI therapy, their challenges in clinical integration and their promise for improving ICI treatment precision and safety, although further research is required for clinical application.
Diabetic cardiomyopathy (DCM) is a major complication of type 1 diabetes mellitus (T1DM) with limited treatment options. Dyrk1a is involved in multiple diseases, comprising neurodegenerative disorders, cancer and diabetes. In addition, Dyrk1a is an emerging therapeutic target. Nonetheless, it remains ambiguous with regard to its role in T1DM‑related DCM. The present study investigated the function and mechanisms of Dyrk1a in DCM. Experimental T1DM was induced through sequential low‑dose streptozotocin administrations via intraperitoneal delivery. The investigation showed conspicuous cardiac upregulation of Dyrk1a protein expression in this T1DM murine model. Pharmacological intervention was performed by employing the Dyrk1a‑targeting compound harmine, administered through oral gavage, which ameliorated cardiac dysfunction characteristic of DCM. This therapeutic efficacy was mechanistically linked to ferroptosis inhibition, which was established through harmine‑mediated attenuation of pathological signatures, namely reduced malondialdehyde accumulation, enhanced glutathione bioavailability, as well as elevated expression of ferroptosis regulators SLC7A11 and GPX4. It is noteworthy that co‑administration of the ferroptosis activator erastin nullified the cardioprotective properties of harmine. Together, these findings establish harmine as an effective modulator of ferroptosis pathways, conferring protection against hyperglycemia‑induced cardiomyocyte injury. Dyrk1a inhibition enhances cardiac function in T1DM by reducing ferroptosis.
Ischemic stroke remains a leading cause of mortality and disability worldwide. Although vascular recanalization is essential for salvaging the ischemic penumbra, subsequent reperfusion may initiate a cascade of secondary brain injury, a pathological process referred to as cerebral ischemia‑reperfusion injury (CIRI). Ferroptosis, an iron‑dependent form of programmed cell death characterized by the excessive accumulation of lipid peroxides and membrane damage, has emerged as a critical driver of neuronal death in CIRI. Growing evidence supports mitochondrial dysfunction as not only a downstream outcome of bioenergetic failure, but also a central regulatory node within the ferroptotic cascade. The present review systematically summarizes how mitochondrial dysfunction increases neuronal susceptibility to ferroptosis across the pathophysiological progression of CIRI, with a particular focus on the underlying mechanisms. Specifically, a multidimensional pathological network composed of multiple mitochondrial abnormalities, including mitochondrial reactive oxygen species bursts, Ca2+ overload and disruption of the mitochondrial quality control system, encompassing mitochondrial biogenesis, mitochondrial dynamics and mitophagy, synergistically amplifies lipid peroxidation and drives neuronal ferroptosis. Finally, advances and future perspectives regarding mitochondria‑centered therapeutic strategies are highlighted, offering novel insights into the development of targeted neuroprotective interventions against CIRI‑induced ferroptosis.
Hyperuricemia (HUA) is primarily attributed to insufficient uric acid (UA) excretion. 6'‑O‑Caffeoylarbutin (CA), the primary bioactive constituent of anti‑gout herbal tea (Que Zui tea), has demonstrated potential urate‑lowering effects; however, its underlying mechanisms require further elucidation. In the present study, a hypoxanthine (HX) and potassium oxonate (PO) induced hyperuricemia (HUA) mouse model was established to assess the effects of different doses of CA. Biochemical analyses, histopathological examination, western blotting and 16S rRNA gene sequencing were conducted to explore the underlying mechanisms. Notably, CA markedly reduced serum uric acid (SUA), serum creatinine (SCr) and blood urea nitrogen (BUN) levels and alleviated renal and intestinal histopathological damage. In the kidney, CA upregulated ATP‑binding cassette sub‑family G member 2 (ABCG2), and downregulated glucose transporter 9 (GLUT9) and urate transporter 1 expression (URAT1). In the intestine, CA increased ABCG2, PDZ domain containing 1 (PDZK1) and tight junction protein expression, while decreasing GLUT9, suggesting improved urate excretion and barrier integrity. 16S ribosomal RNA sequencing revealed that CA was associated with increased gut microbial diversity and reduced abundance of potentially harmful bacteria, including Desulfovibrio. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States‑based prediction suggested accompanying shifts in microbial functions related to transport and metabolism. In conclusion, these findings suggested that CA may exert beneficial effects on HUA involving regulation of renal and intestinal urate transport, improvement of intestinal barrier function and favorable modulation of gut microbiota. CA may therefore serve as a potential candidate for functional food development or therapeutic strategies against HUA.
The ubiquitin‑proteasome system maintains cellular protein turnover and quality control through the coordinated action of ubiquitin ligases and deubiquitinating enzymes (DUBs). While the functions of E3 ubiquitin ligases have been extensively investigated in renal disease, the ~100 human DUBs distributed across seven structurally distinct families have recently emerged as important regulators of renal physiology and pathology. The present review organizes current knowledge of DUB‑mediated regulation in kidney disease around functional themes rather than individual disease categories. The present review discusses how DUBs regulate inflammatory signaling, TGF‑β‑mediated fibrotic responses, epithelial‑to‑mesenchymal transition (EMT), mitochondrial homeostasis, multiple forms of programmed cell death, podocyte homeostasis, and oncogenic pathways in renal cell carcinoma. Several DUBs, including A20 (TNFAIP3), CYLD, USP25 and OTUD5, restrain inflammation and fibrosis, whereas USP11, OTUD1, and USP22 promote disease progression through substrate stabilization. The translational landscape of DUB inhibitors, PROTAC degraders, and the DUBTAC platform for targeted protein stabilization, along with the selectivity and delivery challenges that remain, were discussed. Key unanswered questions, including cell‑type‑specific DUB functions, ubiquitin chain linkage context, and the therapeutic window for DUB modulation in the kidney, are outlined as priorities for future investigation.
Myopia is now recognized as a progressive, potentially sight‑threatening disease rather than just a refractive error, with its prevalence rising rapidly worldwide due to its high occurrence, major vision losses and huge public health cost. The World Health Organization estimates that 2.6 billion individuals in the world were myopic in 2020 this figure is projected to increase to 3.364 billion by 2030. Although myopia may be better controlled in its early stages, it may not be completely reversed at this time. Of all of the methods for controlling myopia, atropine, a muscarinic receptor antagonist, remains an effective pharmacological option for slowing myopia progression in children. However, the mechanisms of action of atropine remain to be fully elucidated. This review provided a systematic review for myopia epidemiology, pathogenesis, the effects and side effects, as well as up‑to‑date possible mechanisms, in the hope of facilitating that researchers in this field elucidate its underlying mechanisms so that clinical ophthalmologists may be able to better control this disease.
Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the Transwell migration and invasion assay experiments shown in Figs. 3D, 6D and F, and 7G and I contained three sets of overlapping sections of data, such that data which were intended to show the results of differently performed experiments had apparently been derived from the same original sources. In addition, the 'si‑FSCN1' data panel for the migration assay experiments shown in Fig. 6D apparently reappeared in Fig. 6 of another paper written by different authors at different research institutes, which was submitted at a later date to the journal Medical Science Monitor. The authors have been contacted by the Editorial Office to offer an explanation for the apparent anomalies in the presentation of the data in this paper, and we are awaiting their response. Owing to the fact that the Editorial Office has been made aware of potential issues surrounding the scientific integrity of this paper, we are issuing an Expression of Concern to notify readers of this potential problem while the Editorial Office continues to investigate this matter further. [Molecular Medicine Reports 22: 5282‑5292, 2020; DOI: 10.3892/mmr.2020.11592].
