Molecular medicine reports最新文献

Neuroinflammation is a central component of the pathophysiology of ischemic stroke (IS). Suppressing excessive inflammatory responses after stroke can markedly improve patient outcomes. Interleukin‑6 (IL‑6), a key mediator of the inflammatory cascade, serves a notable role in the pathological process of acute IS through multiple mechanisms. Elevated serum IL‑6 levels serve as an important biomarker for predicting the onset and recurrence of IS and are closely associated with disease severity and prognosis. Anti‑inflammatory interventions are notably important during the acute phase and secondary prevention of stroke. Currently, therapeutic strategies targeting the IL‑6/IL‑6R signaling axis are under investigation and have shown promising clinical potential. The present review summarizes the important role of IL‑6 in neuroinflammation associated with IS, its association with disease severity and prognosis and previous advances in anti‑inflammatory therapeutic strategies targeting the IL‑6/IL‑6R pathway during both the acute phase and secondary prevention of IS.

Following the publication of the above paper, the authors contacted the Editor to explain that they had made a couple of inadvertent errors in assembling the data in Figs. 1B and 2B. Specifically, the following issues were identified: first, the immunohistochemical staining images representing CD31 in Fig. 1B on p. 3434 were chosen from the wrong dataset; secondly, the immunohistochemical staining images representing HIF‑1α in Fig. 2B on p. 3435 were similarly included in this figure incorrectly. After having performed an  independent analysis of these data in the Editorial Office, it came to light that certain of the data featured in Fig. 2B had been submitted for publication at around the same time in an article featuring some of the same authors to the journal PLoS One. However, the authors were able to consult their original data, and the revised versions of Figs. 1 and 2, now featuring all the correct data for Figs. 1B and 2B, are shown on the next two pages. Note that these errors did not adversely affect either the results or the overall conclusions reported in this study. All the authors agree with the publication of this corrigendum, and are grateful to the Editor of Molecular Medicine Reports for allowing them the opportunity to publish this. They also wish to apologize to the readership of the Journal for any inconvenience caused. [Molecular Medicine Reports 12: 3432‑3438, 2015; DOI: 10.3892/mmr.2015.3815]

Asthenozoospermia (AZS) is one of the most common causes of male infertility, and the decreased expression and function of cation channel of sperm (CatSper) in the sperm contributes to the pathology of AZS. Phenylethanoid glycosides, such as echinacoside (ECH), a compound derived from Cistanche tubulosa, exhibit therapeutic potential for AZS. However, the underlying mechanisms of ECH treatment on AZS remain to be fully elucidated. The ornidazole‑induced AZS model rats (AZS rats) were treated with ECH in vivo and human sperm were exposed to ECH in vitro. Computer‑assisted semen analysis was used to assess sperm motility. The functional characteristics of epididymal sperm were evaluated by analyzing hyperactivation and acrosome reaction. Reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR), western blotting and calcium imaging analyses were used to analyze the expression and function of CatSper channels. In addition, RT‑qPCR, western blotting and chromatin immunoprecipitation‑qPCR were used to investigate the Sex‑determining region Y‑related high‑mobility‑group box family, member 5 (Sox5)‑mediated transcriptional activation of the CatSper gene. It was found that ECH treatment enhanced sperm motility, hyperactivation and acrosome reaction in AZS rats. In addition, ECH upregulated the expression and function of the four α subunits of CatSper channel, CatSper1 to CatSper4, in model rats. Furthermore, ECH treatment increased the protein expression of Sox5 and its binding to the CatSper1 gene promoter region in the testes of AZS rats. In vitro results further suggested that ECH treatment improved sperm motility and CatSper function in the sperm samples from both healthy subjects and patients with idiopathic AZS (iAZS). The present findings suggest that ECH treatment exerts certain therapeutic effects on iAZS through the functional upregulation of CatSper channels in the sperm. These findings position ECH as a promising complementary and alternative medicine therapeutic for enhancing sperm function and managing iAZS in clinical practice.

With the aging of the population, the incidence of postmenopausal osteoporosis (PMOP) is increasing. Extracts from Artemisiae Scopariae Herba, also known as Yinchen (YC), promote osteogenic differentiation and bone formation; however, the specific mechanism is unclear. The present study aimed to investigate the effects and mechanism of YC on PMOP. Ultra‑performance liquid chromatography‑tandem mass spectrometry was used to determine the potential predominant components of YC, and an ovariectomized (OVX) mouse model was established to evaluate the effects of YC on PMOP and its potential mechanisms. Initially, the therapeutic effect of YC on PMOP was assessed by micro‑CT bone analysis, pathological observation and ELISA detection. Combined with serum ELISA, reverse transcription‑quantitative PCR and immunohistochemical staining, the potential key anti‑PMOP pathway of YC was explored. A total of 2,072 compounds were identified in YC. The main active components of YC included chlorogenic acid, ferulic acid and caffeic acid. Experimental studies provided evidence that YC may improve bone loss and bone microstructure deterioration caused by ovariectomy. YC treatment also upregulated serum estrogen levels, and the expression of osteoprotegerin, runt‑related transcription factor 2 and glutathione peroxidase 4 (Gpx4) in bone tissue. Ovariectomy led to abnormal iron metabolism and increase the accumulation of lipid peroxides. YC reduced liver iron deposition, restored glutathione levels, and downregulated serum tartrate‑resistant acid phosphatase, osteocalcin, ferritin and hepcidin levels in mice. In addition, YC reversed the decreased expression of nuclear factor erythroid 2‑related factor 2 (Nrf2), solute carrier family 7 member 11 (Slc7a11) and Gpx4 in the bone tissues of OVX mice. In conclusion, the present study suggested the effectiveness of YC in potentially reducing ovariectomy‑induced osteoporosis in mice. YC promoted bone formation and improved bone microstructure, potentially by inhibiting ferroptosis via activation of the Nrf2/Slc7a11/Gpx4 pathway in OVX mice.

Doxorubicin (DOX) is an effective anthracycline agent used to combat a number of neoplastic diseases. However, DOX causes cardiovascular toxicity in juvenile and young adult survivors of cancer that can lead to future cardiomyopathy. Thus, it is important to address the cardiovascular toxicity caused by DOX to improve the long‑term health of patients with cancer. Soluble epoxide hydrolase (sEH) and cyclooxygenase‑2 (COX‑2) are implicated in cardiovascular diseases by impairing vascular health and promoting the transition of endothelial cells to mesenchymal cells. Given the role of sEH and COX‑2 in endothelial‑to‑mesenchymal transition (EndMT)‑derived cardiovascular toxicity, the present study aimed to investigate the effect of a dual sEH/COX‑2 inhibitor, 4‑[5‑phenyl‑3‑[3‑[[[[4‑(trifluoromethyl)phenyl] amino]carbonyl]amino]propyl]‑1H‑pyrazol‑1‑yl]‑benzenesulfonamide (PTUPB), on DOX‑induced EndMT‑derived vascular and cardiac toxicity. The mitigating effect of PTUPB on DOX‑induced cardiovascular toxicity was explored in zebrafish. The cardiovascular parameters were measured using the Viewpoint MicroZebralab software. Additionally, the effect of PTUPB on DOX‑induced EndMT was assessed in human endothelial cells. The data from the present study indicated that the inhibition of sEH and COX‑2 using PTUPB reduced DOX‑induced EndMT and vascular toxicity. The data also demonstrated that PTUPB improved cardiac function and morphology in zebrafish incubated with DOX. The results of the present study showed that PTUPB downregulated inflammation and oxidative stress markers, which contributed to the improvement in DOX‑induced cardiovascular toxicity. In conclusion, the findings of the present study indicated that the suppression of sEH/COX‑2 using PTUPB reduced DOX‑induced EndMT and the resulting vascular and cardiac toxicity.

Allergic rhinitis (AR) is a chronic inflammatory disorder of the nasal mucosa, often a comorbid condition with asthma, posing notable challenges for treatment. Current therapies, including corticosteroids and antihistamines, primarily target nasal symptoms but exhibit limited efficacy against concurrent asthma and systemic inflammation. Saponins, a class of bioactive plant‑derived compounds, have garnered attention for their pleiotropic effects, including immunomodulation, anti‑inflammatory activity and antioxidant properties. Saponins, such as ginsenosides, notoginsenosides, astragalosides, saikosaponins and platycodins, modulate key molecular pathways in AR, including T helper 1/2 cell balance, mast cell stabilization and NF‑κB signaling. Their multi‑target action and low toxicity profile give them advantages such as metabolic compatibility, reduced polypharmacy risks and mucosal protection. The present review highlighted the mechanistic insights into saponin‑mediated alleviation of AR and asthma, focusing on their molecular targets, signaling pathways and potential for clinical translation. The present review also discussed current limitations and future directions for the development of saponin‑based therapeutics, providing a potential foundation for novel strategies in allergic airway diseases in the future.

Sepsis is a systemic inflammatory disorder characterized by multi‑organ dysfunction following infection. Sepsis‑induced cardiomyopathy (SIC) represents a prevalent complication that markedly contributes to in‑hospital mortality. The NOD‑like receptor protein 3 (NLRP3) inflammasome serves as an important regulator in SIC pathogenesis, directly impairing cardiac function through multiple mechanisms: i) Driving cytokine storms; ii) inducing cardiomyocyte pyroptosis and apoptosis; iii) disrupting mitochondrial homeostasis; and iv) suppressing autophagy. Molecularly‑targeted NLRP3 inhibitors have been developed, such as MCC950, curcumin, indole‑3‑propionic acid and carvacrol, which have demonstrated cardioprotective effects in cellular and animal models of SIC. Further exploration of NLRP3 mechanisms and resulting therapeutic targets may yield novel strategies for SIC diagnosis and clinical management. The present review examined NLRP3‑mediated pathways involving inflammation, programmed cell death and mitophagy in SIC pathogenesis, summarized pharmacological interventions targeting these pathways and highlighted previous advances in NLRP3 research to inform future therapeutic development and clinical translation.

Ulcerative colitis (UC) is a chronic autoimmune disease characterized by mucosal inflammation and disruption of the intestinal barrier. Current therapies often produce adverse effects, underscoring the need for novel treatment options. Naringin, a flavonoid from Citrus aurantium L., has shown anti‑inflammatory potential in inflammatory bowel disease. However, its role in UC via the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway remains elusive. The present study investigated the therapeutic effects of naringin on UC, with a focus on JAK2/STAT3 signaling and intestinal barrier restoration. The present study employed a dextran sulfate sodium (DSS)‑induced colitis mouse model and IL‑6‑stimulated Caco‑2 cells. Mice were administered 3% DSS for 10 days along with naringin (40 mg/kg) or mesalazine (0.2 g/kg) treatment. Disease activity index (DAI), histopathology, expression of tight junction proteins zona occludens‑1 (ZO‑1) and occludin and JAK2/STAT3 pathway protein activation were evaluated. In Caco‑2 cells, transepithelial electrical resistance (TEER) and fluorescein isothiocyanate‑dextran 4 kDa (FD‑4) permeability assays assessed barrier function, with STAT3 silencing supporting pathway involvement. Naringin markedly alleviated DSS‑induced colitis, reducing weight loss, colon shortening, DAI and histological scores. Furthermore, naringin restored ZO‑1 and occludin expression while suppressing JAK2/STAT3 phosphorylation in colon tissues. In Caco‑2 cells, naringin reversed IL‑6‑induced reductions in TEER and increases in FD‑4 permeability, while enhancing tight junction fluorescence. Furthermore, STAT3 silencing in combination with naringin led to a further decrease in the p‑JAK2/JAK2 ratio compared with that in the IL‑6 group (though to a lesser extent than naringin alone), consistent with the involvement of the JAK2/STAT3 pathway. Collectively, these findings demonstrate that naringin ameliorates UC by promoting intestinal barrier repair through suppression of JAK2/STAT3 activation, highlighting its therapeutic potential for UC.

Splicing factor 3a subunit 2 (SF3A2) has been implicated in an increasing number of tumor types; however, at present, its role in clear cell renal cell carcinoma (ccRCC) has yet to be fully elucidated. Therefore, the aim of the present study was to preliminarily explore the putative function of SF3A2 in ccRCC. To meet this aim, SF3A2 expression in ccRCC tissues was analyzed using The Cancer Genome Atlas Kidney Renal Clear Cell Carcinoma dataset and conducted reverse transcription‑quantitative PCR, western blotting and immunohistochemical staining of ccRCC cell models to validate its functional roles. To evaluate the impact of SF3A2 expression on the proliferation, migration and invasion of ccRCC cells, Cell Counting Kit‑8 assays, colony formation assays, Transwell assays and an in vivo xenograft model were employed. Furthermore, western blot analysis was performed to explore which proteins may be involved in the underlying mechanisms of the effects of SF3A2 in ccRCC progression. SF3A2 was found to be markedly upregulated in ccRCC cells and tissues, and its high expression was associated with poor prognosis. The functional assays and in vivo experiments revealed that SF3A2 knockdown inhibited the proliferation, migration and invasion of the ccRCC cells, whereas its overexpression enhanced these processes. In terms of the underlying mechanism, SF3A2 was shown to promote ccRCC progression via activation of the AKT signaling pathway. In conclusion, the present study identified SF3A2 upregulation as a prognostic marker in ccRCC, which was associated with poor clinical outcomes and accelerated tumor progression. Mechanistically, SF3A2 exerted tumor‑promoting effects through the AKT signaling pathway. Taken together, these findings positioned SF3A2 as a dual‑functional biomarker with translational potential, facilitating prognostic stratification and presenting therapeutic targeting opportunities for ccRCC management.

Ferroptosis is an iron‑dependent form of cell death associated with liver pathologies. However, its role in chronic cholestasis remains to be fully elucidated. The present study therefore investigated the pathological mechanism of ferroptosis in a rat model of α‑naphthyl isothiocyanate (ANIT)‑induced chronic cholestasis and evaluated the therapeutic potential of the iron chelator deferoxamine (DFO). Wistar rats were used to establish a chronic cholestasis model via ANIT administration, with a subset of animals receiving DFO treatment. Wistar rats that were subjected to chronic ANIT exposure were found to develop severe liver injury, characterized by impaired function, inflammation and fibrosis. In addition, pronounced iron deposition and hallmark features of ferroptosis, including elevated lipid peroxidation, depleted glutathione, and aberrant expression of acyl‑CoA synthetase long‑chain family member 4 and cyclooxygenase 2, were observed. Ultrastructural analysis revealed distinctive mitochondrial abnormalities consistent with ferroptosis. Mechanistically, these changes appeared to be mediated by suppression of the Kelch‑like ECH‑associated protein 1/nuclear factor erythroid 2‑related factor 2/heme oxygenase 1 antioxidant pathway and dysregulation of key iron metabolism proteins, including transferrin receptor 1 and ferroportin 1. Intervention with DFO markedly ameliorated the cholestatic injury, reduced iron overload and lipid peroxidation, mitigated mitochondrial damage, and normalized the expression of key proteins involved in ferroptosis, antioxidant defense and iron homeostasis. Taken together, these findings suggested that ferroptosis may be a key pathological mechanism in chronic cholestasis, driven by the concurrent disruption of antioxidant and iron metabolic capacities in hepatocytes. Therefore, targeting iron overload may be a promising therapeutic strategy for cholestasis.