International Journal Of Molecular Medicine[JOURNAL]
Sun
200 papers
Arsenic exposure and skin cancer: Mechanisms, clinical evidence and public health implications (Review).
Andreikos DA, Aschner M, Ziogas DC … +2 more , Tsatsakis A, Spandidos DA
Int J Mol Med · 2026 Aug · PMID 42318967 · Full text
Skin is among the most frequent sites of cancer diagnosis, and the global incidence of skin cancer continues to rise despite extensive public health initiatives and preventive strategies. Arsenic, a ubiquitous environmen...
Skin is among the most frequent sites of cancer diagnosis, and the global incidence of skin cancer continues to rise despite extensive public health initiatives and preventive strategies. Arsenic, a ubiquitous environmental metalloid classified as a Group 1 carcinogen, remains an important concern due to widespread exposure through contaminated drinking water, food sources and occupational contact. Arsenic‑associated skin carcinogenesis involves complex, interdependent molecular processes and has been linked to the disruption of redox signalling, altered DNA damage signalling and repair responses as well as epigenetic reprogramming. In keratinocytes, arsenic perturbs redox and stress‑response pathways and may disrupt genome maintenance and cellular stress signalling in experimental systems. Arsenic may also alter microRNA networks and affect telomere and mitochondrial homeostasis, although the contribution of these processes to malignant transformation remains context‑dependent; in melanoma, the carcinogenic mechanisms of arsenic are less well characterized. Clinically, arsenic is recognized as a carcinogen in non‑melanoma skin cancer (NMSC) and evidence from high‑exposure endemic regions, together with occupational cohorts, suggest a dose‑responsive association. For melanoma, clinical evidence is more heterogeneous and subject to substantial potential confounding, although some studies suggest modest risk elevation in high‑exposure or occupational settings. Collectively, convergent mechanistic, experimental and epidemiological data support arsenic as an independent carcinogen, particularly in NMSC. These findings underscore the need for heightened clinical vigilance, particularly in exposed populations, and call for renewed public health strategies and regulatory frameworks to mitigate the persistent global burden of arsenic‑associated skin cancer.
Targeting glutathione metabolism for tumor radiosensitization (Review).
Xu H, Du M, Liang X … +2 more , Xiao X, Chen Z
Int J Mol Med · 2026 Aug · PMID 42318964 · Full text
Radiotherapy represents a cornerstone treatment modality in oncology and primarily mediates tumor cell death through the generation of reactive oxygen species (ROS). Nevertheless, elevated glutathione (GSH) levels within...
Radiotherapy represents a cornerstone treatment modality in oncology and primarily mediates tumor cell death through the generation of reactive oxygen species (ROS). Nevertheless, elevated glutathione (GSH) levels within tumor cells can scavenge these ROS, thereby compromising the efficacy of radiotherapy and promoting the emergence of radioresistance. The contemporary understanding of redox regulation in cancer underscores the strategic relevance of targeting GSH metabolism in the context of radiotherapy. This review comprehensively describes the mechanisms through which GSH metabolism contributes to radioresistance and surveys novel therapeutic approaches aimed at inhibiting GSH synthesis or promoting its depletion to achieve radiosensitization. Both pharmacological compounds and nanotechnology‑enabled delivery systems have been investigated, with an emphasis on their ability to intensify oxidative stress in tumors characterized by high GSHcontent, thus potentially improving radiotherapeutic outcomes.
Moderate downregulation of NDUFA13 promotes cardiomyocytes proliferation and heart regeneration through the glycolysis/c‑Myc/ axis.
Gao Y, Qian N, Jin J … +3 more , Liu J, Wang B, Wang Y
Int J Mol Med · 2026 Aug · PMID 42318953 · Full text
The poor prognosis of heart diseases is largely attributable to the limited proliferative capacity of cardiomyocytes. Cardiomyocyte proliferation and heart regeneration has garnered increasing attention, with a focus on...
The poor prognosis of heart diseases is largely attributable to the limited proliferative capacity of cardiomyocytes. Cardiomyocyte proliferation and heart regeneration has garnered increasing attention, with a focus on the identification of novel therapeutic targets. In the present study, NADH dehydrogenase ubiquinone I α subcomplex 13 (NDUFA13), a subunit protein of mitochondria complex I, was found to serve an important role during this regenerative period of cardiomyocytes. Both and , moderate downregulation of NDUFA13 promoted cardiomyocytes proliferation, increased expression of cell cycle genes, reduced fibrosis and thus benefitted heart regeneration after apical resection. In addition, downregulation of NDUFA13 not only preserved mitochondrial function but also enhanced glycolysis, which is a metabolic shift that is important for modulating the state of cardiomyocytes. Using western blot and reverse transcription‑quantitative PCR, NDUFA13 expression was analyzed at different growth stages in mice and identified its association with cardiomyocyte proliferation. To investigate the role of NDUFA13 , a moderately NDUFA13‑downregulated cell model was developed using siRNA; , Myh6‑cre Ndufa13 mice were generated and performed apical resection surgery. Through proliferation markers, echocardiography and fibrotic staining, the relationship between NDUFA13 and heart regeneration was revealed. To investigate the functional mechanisms, oxidative phosphorylation and glycolytic activity in NDUFA13‑downregulated primary cardiomyocytes was assessed. Upon confirming the changes in glycolytic flux, the expression of c‑Myc and key cell cycle‑related genes was measured. Chromatin immunoprecipitation experiments further revealed c‑Myc binding to the promoter region of . Increasing levels of glycolysis upregulated the expression of c‑Myc, which could bind to the promotor zone of cell cycle gene cyclin D1, thus promoting cardiomyocytes proliferation. Through mitochondrial‑nuclear communication, signals originating from the mitochondria are converted into nuclear transcriptional responses, which in turn drive cellular proliferation. Therefore, the present study demonstrated the key role of NDUFA13 in cardiac regeneration and its potential as a target for heart injury treatment.
Oridonin ameliorates ulcerative colitis by regulating the PI3K/AKT/mTOR signaling pathway to activate autophagy.
Miao Z, Liu B, Zhou X … +6 more , Lu M, Jia N, Zhang H, Qi Y, Tan X, Zhang Q
Int J Mol Med · 2026 Aug · PMID 42318949 · Full text
The present study aimed to investigate the therapeutic effects and underlying mechanism of oridonin (ORI) in ulcerative colitis (UC) using the lipopolysaccharide (LPS)‑induced macrophage inflammatory model and the dextr...
The present study aimed to investigate the therapeutic effects and underlying mechanism of oridonin (ORI) in ulcerative colitis (UC) using the lipopolysaccharide (LPS)‑induced macrophage inflammatory model and the dextran sulfate sodium (DSS)‑induced mouse UC model. Cell Counting Kit‑8 assay was used to determine the appropriate drug concentrations for the experiments. Western blotting and reverse transcription‑quantitative polymerase chain reaction were performed to evaluate the expression levels of proteins and mRNAs related to signaling pathways, autophagy and inflammatory cytokines. The autophagy inhibitor 3‑methyladenine was applied to verify the role of the PI3K/AKT/mTOR pathway. , the disease activity index (DAI) was recorded and colon tissue damage was assessed by hematoxylin and eosin staining. Serum inflammatory cytokines were measured using an enzyme‑linked immunosorbent assay. Network pharmacology based on GeneCards and Traditional Chinese Medicine Systems Pharmacology databases, along with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis, predicted involvement of the PI3K/AKT/mTOR pathway in the pathogenesis of UC, which was further validated by the immunohistochemistry, immunofluorescence and western blotting of colon tissues. The results indicated that ORI significantly reduced the expression of pro‑inflammatory cytokines and increased the anti‑inflammatory cytokine interleukin‑10 in LPS‑stimulated macrophages. In DSS‑induced colitis mice, ORI treatment alleviated body weight loss, decreased DAI scores, improved colon shortening and upregulated the expression of intestinal tight junction proteins. Mechanistically, ORI inhibited the PI3K/AKT/mTOR pathway and altered autophagy‑related molecular markers, as evidenced by increased levels of autophagy‑related (ATG)13, beclin‑1, ATG12, ATG7 and ATG5 as well as decreased expression of p62. In conclusion, ORI alleviates inflammatory responses and mitigates UC‑related pathological changes , which may be associated with suppression of the PI3K/AKT/mTOR pathway and modulation of autophagy‑associated protein markers.
Effects of exercise‑derived extracellular vesicles: Epigenetic regulatory mechanisms and protective roles (Review).
Zhang X, Zhang B
Int J Mol Med · 2026 Aug · PMID 42318940 · Full text
Exercise exerts broad and sustained effects on metabolic homeostasis and overall physiology. However, the circulating mediators connecting localized exercise responses to coordinated systemic adaptation remain poorly def...
Exercise exerts broad and sustained effects on metabolic homeostasis and overall physiology. However, the circulating mediators connecting localized exercise responses to coordinated systemic adaptation remain poorly defined, particularly those involved in inter‑organ communication and long‑term metabolic remodeling. Extracellular vesicles (EVs) have gained significant attention as key mediators in this signaling process, owing to their ability to transport proteins, metabolites, and RNAs between donor and recipient cells. Exercise dynamically modulates EV release, abundance, and cargo composition, suggesting that EVs may act as key mediators of exercise‑induced multisystem adaptation. Notably, exercise may alter the epigenetically active cargo of EVs, regulating epigenetic responses in target organs and ultimately shaping systemic metabolic homeostasis. Given the potential importance of these mechanisms in the long‑term systemic effects of exercise, a comprehensive review of the current evidence is essential. In the present review EV‑mediated epigenetic signaling in exercise is investigated, focusing on how exercise reshapes EV biogenesis and cargo composition, how EV‑associated epigenetic factors regulate recipient‑cell function, and how these processes may contribute to sustained metabolic adaptation. This perspective aims to clarify the mechanistic basis of exercise benefits and to highlight EVs as potential targets for precision diagnostics and therapeutic strategies.
[Retracted] Classical dendritic cells regulate acute lung inflammation and injury in mice with lipopolysaccharide‑induced acute respiratory distress syndrome.
Li L, Dong L, Zhao D … +2 more , Gao F, Yan J
Int J Mol Med · 2026 Aug · PMID 42272266 · Full text
Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that, regarding the lung tissue images shown in Fig. 5B on p. 624, the 'FLT3L+AARDS' and 'DMSO+AARDS' panels contained...
Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that, regarding the lung tissue images shown in Fig. 5B on p. 624, the 'FLT3L+AARDS' and 'DMSO+AARDS' panels contained an overlapping section of data, such that data which were intended to show the results of differently performed experiments had apparently been derived from the same original source. Although the possibility of publishing a corrigendum was considered, upon performing an independent analysis of the data in this paper in the Editorial Office, it came to light that western blot data in Fig. 1A and D had previously been published in a pair of papers in the journal PloS One which were written by different authors at different research institutes. Owing to the fact that the contentious western blot data in the above article were found to be strikingly similar to data that had already been published elsewhere, the Editor of has decided that this paper should instead 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. [International Journal of Molecular Medicine 44: 617‑629, 2019; DOI: 10.3892/ijmm.2019.4208].
[Corrigendum] (‑)‑Epigallocatechin‑3‑gallate attenuates myocardial injury induced by ischemia/reperfusion in diabetic rats and in H9c2 cells under hyperglycemic conditions.
Wu Y, Xia ZY, Zhao B … +6 more , Leng Y, Dou J, Meng QT, Lei SQ, Chen ZZ, Zhu J
Int J Mol Med · 2026 Aug · PMID 42272258 · Full text
Following the publication of the above article, an interested reader drew to the authors' attention that, concerning the Masson trichrome‑stained sections of left ventricles shown in Fig. 6A on p. 395, a portion of the p...
Following the publication of the above article, an interested reader drew to the authors' attention that, concerning the Masson trichrome‑stained sections of left ventricles shown in Fig. 6A on p. 395, a portion of the panel representing the DM+EGCG group (centre panel) contained an overlapping area with a portion of the panel from the DM group (second panel on the left), which was representative of the experiment that lacked EGCG treatment. Upon investigating this figure, the authors have realized that the affected data panels were inadvertently assembled incorrectly. This error arose due to an oversight in image selection made during figure assembly. A revised version of Fig. 6, now showing the correct data panel for the DM+EGCG group (centre panel) in Fig. 6A, is shown on the next page. Also note that the published version of Fig. 6A did not feature labels portraying the different experimental groups in this figure part, and these are now included in the revised figure to improve its clarity. The authors confirm that the error associated with this figure did not have any significant impact on either the results or the conclusions reported in this study, and all the authors agree with the publication of this Corrigendum. The authors are grateful to the Editor of for allowing them the opportunity to publish this Corrigendum; furthermore, they apologize to the readership of the Journal for any inconvenience caused. [International Journal of Molecular Medicine 40: 389‑399, 2017; DOI: 10.3892/ijmm.2017.3014].
Melatonin ameliorates circadian rhythm disruption induced erectile dysfunction by inhibiting oxidative stress mediated pyroptosis via Nrf2/HO‑1 axis.
Yang Q, Li W, Yu Q … +7 more , Shi J, Yang L, Qiao J, Wei X, Gu C, Sun F, Li T
Int J Mol Med · 2026 Aug · PMID 42272256 · Full text
Circadian rhythm disruption (CRD) is highly prevalent in modern society and contributes to numerous disorders, including erectile dysfunction (ED). Melatonin (MT) possesses well‑established functions in regulating circad...
Circadian rhythm disruption (CRD) is highly prevalent in modern society and contributes to numerous disorders, including erectile dysfunction (ED). Melatonin (MT) possesses well‑established functions in regulating circadian rhythm and demonstrating antioxidant ability; however, whether MT could preserve CRD‑induced ED and the underlying mechanism has never been reported. A rat model with CRD‑induced ED was designed by changing light‑dark cycle (2h:2h alteration) and then intraperitoneally administering MT with low (5 mg/kg/day) and high (10 mg/kg/day) dosages. A total of 4 weeks later, rats' erectile function was measured and penile corpus cavernosum was subsequently harvested for analysis. In addition, bioinformatics analysis was performed to filter the possible molecular target, while lipopolysaccharide (LPS)‑treated human umbilical vein endothelial cells (HUVECs) were selected to imitate CRD stimulation in vivo to further verify the underlying molecular mechanism. CRD significantly reduced rats' maximal intracavernous pressure (mICP) and mICP/mean arterial pressure (MAP) ratio, it also inhibited endothelial nitric oxide synthase/nitric oxide/cyclic guanosine monophosphate concentrations and injured normal penile corpus cavernosum structure, suggesting rats' normal erectile function was impaired; however, this CRD‑induced ED was preserved by MT. The and experiments respectively proved that CRD increased oxidative stress of penile corpus cavernosum and HUVECs by reducing nuclear factor erythroid 2‑related factor 2 (Nrf2)/heme oxygenase‑1 (HO‑1) production, while MT increased Nrf2/HO‑1 to inhibit the oxidative stress. Meanwhile, CRD promoted pyroptosis in penile corpus cavernosum and HUVECs by increasing NLR family pyrin domain containing 3 (NLRP3) activation, which was relieved by MT through the attenuation of oxidative stress. Moreover, the reactive oxygen species inhibitor (NAC) inhibited CRD‑induced pyroptosis of HUVECs to preserve normal function, which confirmed that MT alleviated NLRP3‑mediated pyroptosis to preserved CRD‑induced ED by reducing oxidative stress. In conclusion, it was demonstrated that CRD‑induced ED by triggering an oxidative stress‑pyroptosis cascade. Conversely, MT treatment effectively counteracts this pathology by activating the Nrf2/HO‑1 pathway to suppress oxidative stress, thereby attenuating NLRP3‑mediated pyroptosis and ultimately restoring erectile function. These results provide the first systematic evidence for the central role of the oxidative stress‑pyroptosis axis in CRD‑induced ED, establishing a solid theoretical foundation for MT as a promising therapeutic strategy for CRD‑related ED.
Withaferin A, a candidate drug for lupus nephritis, confers renal protection via Pon1‑mediated attenuation of oxidative stress.
Xue M, Feng J, Mao X
Int J Mol Med · 2026 Aug · PMID 42272255 · Full text
Lupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus (SLE). It is characterized by autoantibody deposition and immune complex formation within the kidney, leading to progressive nephron loss and...
Lupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus (SLE). It is characterized by autoantibody deposition and immune complex formation within the kidney, leading to progressive nephron loss and end‑stage renal disease. Suppression of immunology is a cornerstone for managing LN. The present study identified withaferin A (WA) as a promising therapeutic candidate for SLE via connectivity map analysis and validated its efficacy in ameliorating LN in an MRL/lpr mouse model. Candidate drugs for LN were identified via the Connectivity Map database by integrating transcriptomic signatures from GSE135779, GSE162577 and GSE142016. An animal model was established to evaluate the therapeutic efficacy of WA on LN‑associated inflammation and splenic dysfunction, followed by RNA‑sequencing analysis. To elucidate the mechanistic role of PON1 in WA‑mediated protection, siRNA‑mediated knockdown and plasmid‑driven overexpression were performed in HK‑2 cells. Furthermore, the direct impact of WA was assessed using isolated primary B cells. WA improved renal function by mitigating splenic immune cell dysregulation and attenuating renal inflammation. Mechanistically, RNA‑sequencing analysis and functional validation revealed that WA upregulated paraoxonase 1 (Pon1) expression, which in turn alleviates renal injury by decreasing reactive oxygen species via the peroxisome proliferator‑activated receptor signaling pathway. Pon1 activation enhanced cell viability, suppressed inflammatory responses and decreased oxidative stress in HK‑2 cells, underscoring its potential as a novel therapeutic target for LN. Collectively, the findings demonstrate WA is a viable candidate for SLE/LN treatment and Pon1 is a pivotal mediator of its protective effects, thereby providing a dual‑strategy insight for clinical intervention.
Spatial architecture of immunometabolism: Mitochondrial‑organelle interfaces in immune signaling (Review).
Wu Y, Yu H, Xia L … +3 more , Yang L, Zhou Y, Yu Q
Int J Mol Med · 2026 Aug · PMID 42272253 · Full text
Metabolic reprogramming is fundamental to immune cell function, yet the spatial architecture that organizes these metabolic states remains incompletely defined. Rather than functioning as isolated bioenergetic units, mit...
Metabolic reprogramming is fundamental to immune cell function, yet the spatial architecture that organizes these metabolic states remains incompletely defined. Rather than functioning as isolated bioenergetic units, mitochondria act as spatial hubs embedded within dynamic organelle networks that coordinate immuno‑metabolic signaling. In the present review, the structural and functional basis of mitochondrial organelle interfaces were delineated, including membrane contact sites and vesicular trafficking pathways, with the endoplasmic reticulum, lysosomes, peroxisomes, lipid droplets and the nucleus. It was discussed how these interfaces generate specialized microdomains for the localized exchange of calcium, lipids and redox signals, thereby shaping innate and adaptive effector programs. It was further highlighted how mitochondria‑derived vesicles and mitochondria‑containing extracellular vesicles extend this regulatory axis, linking intracellular organelle crosstalk directly to systemic tissue homeostasis. Crucially, maladaptive decoupling of these interface circuits emerges as a recurrent feature of infection, sepsis, cancer, autoimmunity and chronic inflammation diseases. Finally, emerging interface‑targeted therapeutic strategies were evaluated and the technical methodologies required to validate nanoscale interactions were critically assessed. By conceptualizing immunometabolism as a spatially coordinated process, the prsent review provides a comprehensive landscape for decoding immune signaling and identifies tractable avenues for precision immunotherapy.
Urea cycle dysregulation and arginine pathways in the pathogenesis of NAFLD and NASH (Review).
Zhu B, Wang C, Liu P … +4 more , Qu Z, Qi R, Chen S, Niu H
Int J Mol Med · 2026 Aug · PMID 42272250 · Full text
Non‑alcoholic fatty liver disease (NAFLD) and its advanced form, non‑alcoholic steatohepatitis (NASH), are now leading causes of chronic liver disease worldwide. Recent evidence highlights the central role of urea cycle...
Non‑alcoholic fatty liver disease (NAFLD) and its advanced form, non‑alcoholic steatohepatitis (NASH), are now leading causes of chronic liver disease worldwide. Recent evidence highlights the central role of urea cycle and arginine metabolism dysregulation in NAFLD/NASH pathogenesis. Downregulation of key urea cycle enzymes, such as carbamoyl phosphate synthetase 1, ornithine transcarbamylase and argininosuccinate synthase, impairs ammonia detoxification, leading to hyperammonemia, mitochondrial dysfunction and oxidative stress. Epigenetic modifications, notably DNA methylation and histone changes, contribute to this metabolic reprogramming. Aberrant arginine metabolism, particularly the imbalance between urea and nitric oxide (NO) pathways, exacerbates liver inflammation and fibrosis through increased inducible nitric oxide synthase (NOS) activity in macrophages and hepatic stellate cells, driving excessive NO and polyamine production. In contrast, physiological NO signaling via endothelial NOS supports mitochondrial health and metabolic homeostasis. Clinically, urea cycle and arginine metabolites, including blood ammonia and urea cycle metabolites, serve as potential biomarkers for disease severity. Restoring urea cycle function and rebalancing arginine‑NO metabolism through targeted interventions, such as citrulline/arginine supplementation or enzyme modulation, are promising strategies.
Plant‑derived natural products alleviate dexamethasone‑induced skeletal muscle atrophy by modulating FoxO (Review).
Dai W, Wu J, Ma X … +5 more , Wu M, Li K, Gao H, Wang W, Xiao W
Int J Mol Med · 2026 Aug · PMID 42246193 · Full text
Muscle atrophy (MA) is a major global health issue, and systematic strategies for its prevention and treatment are lacking. Diverse factors contribute to MA, amongst which the exogenous over‑supplementation and endogenou...
Muscle atrophy (MA) is a major global health issue, and systematic strategies for its prevention and treatment are lacking. Diverse factors contribute to MA, amongst which the exogenous over‑supplementation and endogenous pathological elevation of glucocorticoids (GCs) are key causes. The present study summarizes MA induced by the GC dexamethasone (DEX) and its molecular mechanisms, including protein metabolism imbalance, mitochondrial dysfunction and abnormalities in epigenetic regulatory proteins, to explore potential therapeutic approaches for MA. FoxO transcription factor serves a central regulatory role in DEX‑induced MA by modulating the ubiquitin‑proteasome system, autophagy‑lysosomal system and energy metabolism pathways. Therefore, FoxO may serve as a critical therapeutic target for DEX‑induced MA. Plant‑derived natural products are promising candidates for the development of clinical drugs for tumors, myocardial infarction and diabetic nephropathy. These products protect against MA by regulating FoxO activity through multiple signaling pathways, including Akt, AMPK, and SIRT. Plant monomer compounds, such as flavonoids, polyphenols and terpenes, exert therapeutic effects and may provide new strategies for the precise prevention and treatment of MA induced by elevated GC levels.
Experimental rodent models of cardiorenal syndrome types 3 and 4: Insights and clinical relevance (Review).
Figueroa SM, Huang S, Reyes-Osorio J … +4 more , Boffa JJ, Amador CA, Chadjichristos CE, Boutin L
Int J Mol Med · 2026 Aug · PMID 42246189 · Full text
Cardiorenal syndrome (CRS) encompasses the bidirectional and complex interaction between cardiac and renal dysfunction. The present review focuses on CRS types 3 and 4, highlighting the negative effects of acute kidney i...
Cardiorenal syndrome (CRS) encompasses the bidirectional and complex interaction between cardiac and renal dysfunction. The present review focuses on CRS types 3 and 4, highlighting the negative effects of acute kidney injury and chronic kidney disease, respectively, on cardiac function. The present review focuses on pathophysiological mechanisms, associating renal impairment with cardiovascular events, paying particular attention to systemic inflammation, oxidative stress, endothelial damage and neurohormonal activation. From fundamental science to clinical applications, the investigation of CRS remains a challenge. In this context, some experimental models mimicking CRS types 3 and 4 have been used, including 5/6 nephrectomy, unilateral ureteral obstruction, renal ischemia‑reperfusion and adenine‑ or cisplatin‑induced kidney injury. While these models are valuable for studying such disease mechanisms, their limitations in mimicking human pathophysiology are discussed, and their strengths and weaknesses are critically addressed. Advancing and refining preclinical models should be prioritized in future research to enhance clinical relevance and accelerate the development of targeted therapies for CRS.
[Retracted] miR‑215 promotes epithelial to mesenchymal transition and proliferation by regulating LEFTY2 in endometrial cancert.
Gao X, Cai Y, An R
Int J Mol Med · 2026 Aug · PMID 42246182 · Full text
Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that western blot data shown in Fig. 1C on p. 1232 were strikingly similar to data in a paper that had previously been...
Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that western blot data shown in Fig. 1C on p. 1232 were strikingly similar to data in a paper that had previously been published in the journal that was written by different authors at different research institutes. Upon performing an independent analysis of the data in this paper in the Editorial Office, it also came to light that the cellular images featured in Fig. 6B on p. 1233 had also previously appeared in another article published in the journal that was similarly written by different authors at different research institutes. Given that the abovementioned data had already been published before the receipt of this paper at , 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. [International Journal of Molecular Medicine 42:1229‑1236, 2018; DOI: 10.3892/ijmm.2018.3703].
Lactate regulates osteoclastogenesis via H3k18la in osteoarthritis.
Fan Z, Fu Q, Sun T … +6 more , Zhong Y, Ma Y, Jian J, Yuan S, Li S, Xu X
Int J Mol Med · 2026 Aug · PMID 42246181 · Full text
Osteoarthritis (OA), characterized by articular cartilage degeneration and subchondral bone remodeling, is a notable cause of disability globally. The present study aimed to explore the role and mechanism of histone H3 l...
Osteoarthritis (OA), characterized by articular cartilage degeneration and subchondral bone remodeling, is a notable cause of disability globally. The present study aimed to explore the role and mechanism of histone H3 lysine 18 lactylation (H3K18la) in OA osteoclast differentiation and verify the therapeutic potential of targeting this pathway. Using a mouse OA model (anterior cruciate ligament transection), RAW264.7 cell experiments, oxmacid‑mediated lactate inhibition and cleavage under targets and tagmentation to map genomic targets, the present study demonstrated elevated H3K18la in OA joint osteoclasts, associated with reduced bone mineral density and aggravated subchondral bone destruction. Analysis of TRAP and lactate indicated that RANKL‑induced osteoclast differentiation increased lactate production, enhancing H3K18la; oxmacid inhibited both of these processes. H3K18la was enriched at the acid phosphatase 5 promoter and directly promoted its transcription. Local oxmacid injection in OA mice decreased osteoclast numbers and alleviated subchondral bone loss. Thus, H3K18la was a key metabolic‑epigenetic mediator linking glycolysis to osteoclast differentiation, representing a novel OA therapeutic target.
[Expression of Concern] Novel insights into the role of HSP90 in cytoprotection of HS against chemical hypoxia‑induced injury in H9c2 cardiac myocytes.
Yang Z, Yang C, Xiao L … +7 more , Liao X, Lan A, Wang X, Guo R, Chen P, Hu C, Feng J
Int J Mol Med · 2026 Aug · PMID 42246179 · Full text
Following the publication of this paper, and an Expression of Concern statement that was published to draw attention to the fact that the Editorial Office are in the process of consulting the authors regarding the fact t...
Following the publication of this paper, and an Expression of Concern statement that was published to draw attention to the fact that the Editorial Office are in the process of consulting the authors regarding the fact that the photos shown in Fig. 5B and D were apparently matching images (doi: 10.3892/ijmm.2025.5618), we have been contacted again by another reader who has highlighted that Fig. 5C and F also contain an overlapping section, albeit that the image has been rotated through 90° and flipped vertically in panel (F). We have contacted the authors again, asking them to provide an explanation for the apparent anomalies in the presentation of Fig. 5 in this paper, although up to this time, no response from them has been forthcoming. Owing to the fact that the Editorial Office has been made aware of these potential issues surrounding the scientific integrity of this paper, we are issuing a second Expression of Concern statement to notify readers of this potential problem while the Editorial Office continues to investigate this matter further. [International Journal of Molecular Medicine 28: 397‑403, 2011; DOI: 10.3892/ijmm.2011.682].
Microbiota‑derived indole‑3‑propionic acid reprograms bone marrow stem cell fate via PPARγ suppression to rescue osteoporosis.
Bai J, Wang R, Fan J … +8 more , Su S, Si G, You Q, Sun A, Hu D, Gao S, Lv Y, Zhou F
Int J Mol Med · 2026 Aug · PMID 42246175 · Full text
Osteoporosis (OP) is increasingly recognised as a disorder driven by impaired lineage allocation of bone marrow stromal cells (BMSCs), characterised by a shift from osteogenesis toward adipogenesis under conditions such...
Osteoporosis (OP) is increasingly recognised as a disorder driven by impaired lineage allocation of bone marrow stromal cells (BMSCs), characterised by a shift from osteogenesis toward adipogenesis under conditions such as oestrogen deficiency and oxidative stress. Although gut microbiota‑derived metabolites have emerged as critical regulators of skeletal homeostasis, their direct role in BMSC fate determination remains poorly understood. In the present study, indole‑3‑propionic acid (IPA) was identified, a metabolite produced by , as a key regulator of bone‑fat balance. Integrative analyses combining 16S rRNA sequencing, metabolomics, transcriptomics and functional assays revealed that IPA levels were significantly reduced in ovariectomised mice and positively correlated with bone mass. Functionally, IPA protected BMSCs from oxidative stress‑induced apoptosis, restored osteogenic capacity, and suppressed adipogenic differentiation. Mechanistically, RNA sequencing and molecular docking analyses demonstrated that IPA modulates the peroxisome proliferator‑activated receptor gamma (PPARγ) signalling pathway, thereby reprogramming BMSC lineage commitment. , oral administration of IPA markedly improved trabecular bone microarchitecture, enhanced bone formation, and corrected marrow adiposity without detectable systemic toxicity. Collectively, the present findings identified IPA as a previously under‑recognised microbiota‑derived metabolite that maintains skeletal homeostasis by restoring the osteogenic‑adipogenic balance through suppression of PPARγ signalling. The present study uncovers a mechanistic link between gut microbial metabolism and BMSC fate regulation and highlights IPA as a promising therapeutic candidate for OP.
Functional hydrogels in cardiovascular therapy: Design, applications and clinical challenges (Review).
Yang Z, Li J, Zhao L … +4 more , Zhang D, Yan C, Liu D, Han Y
Int J Mol Med · 2026 Aug · PMID 42246172 · Full text
Cardiovascular disease (CVD) is the leading cause of mortality worldwide, and conventional treatments (such as pharmacotherapy, stents and bypass surgery) have limited capacity to repair damaged cardiovascular tissue. Hy...
Cardiovascular disease (CVD) is the leading cause of mortality worldwide, and conventional treatments (such as pharmacotherapy, stents and bypass surgery) have limited capacity to repair damaged cardiovascular tissue. Hydrogels, as biocompatible three‑dimensional network materials, demonstrate potential for the treatment of CVD. The present review summarizes functional hydrogels for CVD treatment, including their preparation, applications, current challenges and future perspectives. Hydrogel materials comprise natural polymers, synthetic polymers and composite systems, each with distinct advantages and limitations: Natural polymers offer good biocompatibility but exhibit poor mechanical strength; synthetic polymers provide tunable properties but lack inherent bioactivity; composites combine the advantages of both but are more complex to manufacture. Stimuli‑responsive hydrogels respond to environmental cues and enable on‑demand therapeutic delivery. In terms of clinical applications, hydrogels have potential for post‑infarction myocardial repair, vascular regeneration, heart valve repair and regeneration and heart failure management. They serve as scaffolds, as well as cell and drug delivery carriers. Nevertheless, hydrogels face challenges in clinical translation, including safety, long‑term biocompatibility, mechanical and electrical compatibility with host tissue, thrombogenicity, large‑scale manufacturing, integration with standard care and regulatory approval. In the future, hydrogel systems are may evolve toward stimuli‑responsive, self‑regulating, adaptive and personalized designs, integrate with emerging therapeutic strategies (such as gene therapy, cell therapy, and RNA‑based therapeutics) and be used in conjunction with existing medical devices (stents, vascular grafts, pacemakers, and ventricular assist devices), thereby becoming an important platform for cardiovascular regenerative therapy.
Multi‑scale experimental models for the study of angiogenesis (Review).
Yu Q, Hu J, Yuan S … +4 more , Gan J, Luo M, Wu J, Wang L
Int J Mol Med · 2026 Aug · PMID 42212390 · Full text
Angiogenesis is defined as the formation of new blood vessels originating from pre‑existing vasculature and serves a critical role in physiological developmental processes. In addition, angiogenesis serves important role...
Angiogenesis is defined as the formation of new blood vessels originating from pre‑existing vasculature and serves a critical role in physiological developmental processes. In addition, angiogenesis serves important roles in various pathological conditions, such as diabetic retinopathy, psoriasis, and tumor progression and metastasis. A primary challenge in this field remains the selection of appropriate assays to elucidate the underlying molecular mechanisms, evaluate the efficacy of potential therapeutic agents and identify viable targets within the angiogenic pathway. Given that heterogeneity exists not only amongst endothelial cells themselves but also within the specific microenvironment under investigation, it is crucial to select appropriate assay conditions and cell types that can most accurately reflect the angiogenic pathology being studied. Therefore, the present review documents the advantages and limitations of the principal angiogenesis assays currently in use, including those for the proliferation, migration, two‑dimensional tube formation and three‑dimensional tubulogenesis of endothelial cells , vessel outgrowth from retinal explants, and aortic rings and assays (such as hindlimb ischemia models, corneal neovascularization assays, retinal vascularization assays, zebrafish models, chick chorioallantoic membrane assays and tumor angiogenesis models). The aim of the present review is to perform a comprehensive analysis of angiogenesis models to establish a foundational framework for subsequent experimental studies on angiogenesis‑related pathologies.
Targeting lactylation in hepatocellular carcinoma: Mechanistic insights and therapeutic opportunities (Review).
Chen L, Gao F, Mei Q … +3 more , Li Y, Cai Q, Feng X
Int J Mol Med · 2026 Aug · PMID 42212387 · Full text
Hepatocellular carcinoma (HCC) is a malignant tumor characterized by profound metabolic reprogramming and a pronounced Warburg effect, resulting in excessive lactate accumulation in the tumor microenvironment (TME). Trad...
Hepatocellular carcinoma (HCC) is a malignant tumor characterized by profound metabolic reprogramming and a pronounced Warburg effect, resulting in excessive lactate accumulation in the tumor microenvironment (TME). Traditionally regarded as a metabolic byproduct, lactate has recently been recognized as a substrate for lactylation, offering new insights into tumorigenesis and cancer progression. The present review systematically summarized the molecular basis of lactylation and delineated its regulatory network in HCC. It focused on how lactylation contributes to the malignant phenotype of HCC cells and reshapes the TME, highlighting its roles in tumor progression and metabolic‑immune interactions. Based on current evidence, lactylation‑related features show potential translational value in the diagnosis, treatment and prognosis of HCC. A deeper understanding of lactylation mechanisms may provide novel insights and strategies for precision therapy in HCC.
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