Renal tubular injury has emerged as a critical determinant in the pathogenesis of diabetic nephropathy (DN). Ferroptosis, a recently characterized mode of iron‑dependent regulated cell death, has been implicated in the development of renal tubular damage. Dapagliflozin (DAPA), a sodium‑glucose cotransporter 2 inhibitor, has demonstrated efficacy in attenuating DN progression and preserving renal function. The present study sought to elucidate the inhibitory mechanisms by which DAPA modulates ferroptosis in DN. To this aim, the expression profiles of key molecular markers within the ferroptosis cascade were systematically evaluated using 6‑week‑old male C57BL/6J mice and high‑glucose‑cultured human renal tubular epithelial cells as experimental models. The findings revealed that DAPA notably ameliorated renal histopathological alterations, upregulated the expression of solute carrier family 7 member 11, glutathione peroxidase 4 and ferritin heavy chain 1, whilst concomitantly downregulating transferrin receptor 1. These effects were mediated through the activation of nuclear factor erythroid 2‑related factor 2 (Nrf2) and heme oxygenase‑1 (HO‑1) in C57BL/6J mice. Collectively, these data indicate that the reno‑protective effects of DAPA in DN may be attributable to the suppression of ferroptosis via activation of the Nrf2/HO‑1 signaling axis.

Ferroptosis, an iron‑dependent form of regulated cell death driven by lipid peroxidation, has emerged as a key mechanism underlying tissue degeneration and impaired regeneration in musculoskeletal disorders. Although ferroptosis is associated with conditions such as tendinopathy, sarcopenia, osteoarthritis and osteoporosis, systematic synthesis connecting molecular mechanisms with disease‑specific contexts and translational implications remains limited. The present review summarizes the fundamental molecular mechanisms of ferroptosis, including iron metabolism dysregulation, lipid peroxidation processes and antioxidant defense systems centered on GPX4 and glutathione. Subsequently, the involvement of ferroptosis across major musculoskeletal diseases was investigated, highlighting how iron imbalance, oxidative stress and age‑related alterations collectively contribute to tissue dysfunction and degeneration. Particular emphasis is placed on aging‑associated changes in iron homeostasis and antioxidant capacity as potential amplifiers of ferroptotic vulnerability in musculoskeletal tissues. Experimental modeling strategies and pharmacological modulation approaches used to investigate ferroptosis in musculoskeletal research are further discussed and their mechanistic relevance and translational challenges are analyzed. Finally, the present review outlines emerging therapeutic perspectives and future research directions aimed at improving the understanding and potential clinical targeting of ferroptosis in musculoskeletal disorders. By providing a structured and integrative synthesis, the present review clarifies the role of ferroptosis at the intersection of iron dysregulation, redox imbalance and musculoskeletal decline.

Ferroptosis exerts a recognized role in the pathogenesis of acute kidney injury (AKI) and is considered a critical target for improving its prognosis. Emerging evidence indicates that ferroptosis serves a pivotal role in pathogenesis of AKI and targeting ferroptosis provides a promising therapeutic strategy in treatment of AKI. In the present study, ligustroflavone (LIG), which is a flavonoid with oral activity extracted from Ligustrum lucidum, was found to inhibit ferroptosis through activation of nuclear factor erythroid 2‑related factor 2 (NRF2) via inhibition of GSK3β in vivo and in vitro. In vivo, cisplatin (CDDP) and ischemia‑reperfusion injury (IRI)‑induced murine models of AKI were constructed to evaluate the possible effects of LIG. In vitro, the protective effects of LIG were assessed in cultured mouse renal proximal tubular epithelial cells (TKPTs). Immunostaining, reverse transcription‑quantitative PCR, western blot and lipid peroxidation assays were performed to detect renal tubular injury and ferroptosis. The results of the present study demonstrated that LIG administration significantly ameliorated CDDP or IRI induced renal damage in mice. Additionally, administration of LIG significantly ameliorated lipid peroxide accumulation and inhibited ferroptosis in the kidneys of AKI mice. In vitro, LIG treatment markedly ameliorated CDDP‑induced lipid peroxidation and ferroptosis in cultured TKPTs via GSK3β inhibition and NRF2 activation. Furthermore, knockout of GSK3β also protected against CDDP‑induced cell death and LIG exerted no additional protective effects in GSK3β‑knockout TKPTs. Together, the present findings offer a new potential strategy for AKI therapies by targeting ferroptosis.

Following the publication of the above article, an interested reader drew to the authors' attention that the β‑actin blots featured for the western blots in Figs. 5A and 8A were apparently the same, even though the samples came from different tissues (liver and brain, respectively). Upon re‑examining their original data, the authors have realized that the control blots were erroneously selected for Fig. 8A; moreover, the same processing error was made with the control blots for Fig. 6A (duplicated from those for Fig. 4A) and Fig. 9A (duplicated from Fig. 7A). The revised versions of Figs. 6, 8 and 9, now showing the correct control western blots in Figs. 6A, 8A and 9A, are shown opposite and on the subsequent page. Note that the errors made in assembling these figures did not affect the overall conclusions reported in the paper. All the authors agree with the publication of this corrigendum, and are grateful to the Editor of International Journal of Molecular Medicine for granting them the opportunity to publish this. Furthermore, they apologize to the readership for any inconvenience caused. [International Journal of Molecular Medicine 27: 319‑327, 2011; DOI: 10.3892/ijmm.2010.581].

The present study explored the protective mechanism of hydromorphone (HM) preconditioning in cerebral ischemia/reperfusion injury (CIRI). An animal model of CIRI was established by middle cerebral artery occlusion/reperfusion in male C57BL/6J mice. An I/R cell model was induced by oxygen‑glucose deprivation/reperfusion. Brain tissue injury and cell injury were evaluated by hematoxylin and eosin staining, 2,3,5‑triphenyltetrazolium chloride staining, lactate dehydrogenase testing and a Cell Counting Kit‑8 assay. Nod‑like receptor protein 3 (NLRP3)‑positive expression and caspase‑1 activity were assessed by immunostaining and caspase‑1 activity assays, respectively. Reverse transcription‑quantitative PCR or western blotting were used to quantify the expression levels of microRNA (miR)‑195‑5p, RNA‑binding motif protein 15 (RBM15) and upstream stimulatory factor 2 (USF2). RNA immunoprecipitation (RIP) and dual‑luciferase assays verified the binding between miR‑195‑5p and RBM15, followed by RIP analysis of N6‑methyladenosine (m6A) enrichment on USF2 and quantitative analysis of m6A content. The binding of RBM15 and insulin‑like growth factor 2 mRNA‑binding protein 3 (IGF2BP3) to the USF2 m6A site was analyzed by a dual‑luciferase assay. HM preconditioning inhibited NLRP3‑mediated pyroptosis, alleviated neurological deficits, and reduced inflammatory injury in brain tissue. Mechanistically, hydromorphone (HM) preconditioning targeted RBM15 and reduced IGF2BP3‑mediated m6A modification by upregulating miR‑195‑5p expression, thus decreasing USF2 expression, reducing the enrichment of USF2 on the NLRP3 promoter, and inhibiting NLRP3‑mediated pyroptosis. In conclusion, HM preconditioning may repress NLRP3‑mediated pyroptosis and alleviate CIRI via the effects of miR‑195‑5p/RBM15/USF2.

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 International Journal of Molecular Medicine 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].

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 in vivo and in vitro 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.

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 International Journal of Molecular Medicine 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].

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.

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.