International journal of molecular medicine最新文献

Following the publication of the above paper, it was drawn to the Editor's attention by an interested reader that, regarding the western blot data shown in Fig. 5 on p. 507, the first set of GAPDH bands for the GH3 cell line were strikingly similar to the EGFR protein bands shown for the GT1‑1 cell line in the adjacent set of gels, such that the same data had apparently been used to represent the two different proteins. The authors were contacted by the Editorial Office to offer an explanation for the apparent duplication of data 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 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. [International Journal of Molecular Medicine 47: 500‑510, 2011; DOI: 10.3892/ijmm.2020.4807].

As a key component of the immune system, B cells primarily mediate humoral immunity via the synthesis and secretion of antibodies. In addition, B cells contribute to immune responses via antigen presentation and cytokine secretion. B cell‑targeted therapy has potential for the treatment of autoimmune diseases. However, current B cell‑targeted therapies have limited efficacy when used as monotherapies in clinical settings. In an aim to provide in‑depth understanding of this limitation, the present review discusses the developmental and differentiation pathways of B cells and the mechanisms by which various B cell subsets participate in immune responses, as well as randomized controlled trials on B cell‑targeted therapies conducted on lupus nephritis, an autoimmune disease with a notable inflammatory response. The clinical benefits of these therapies remain modest. This suggests that while B cells may serve a pathogenic role, existing therapies fail to address the fundamental mechanisms underlying disease progression. Targeting the interactions between B and T cells, particularly by inhibiting B cell‑mediated antigen presentation, may represent a promising novel direction for B cell‑targeted therapy.

Osteoarthritis (OA) is one of the most common joint diseases worldwide. Recently, cold‑inducible RNA binding protein (CIRP), a novel identified pro‑inflammatory cytokine, was reportedly increased in the synovial fluid of OA patients. However, its function and the underlying mechanism in OA progression remains unclear. Therefore, the current study investigated the role of CIRP in the progression of OA. It was observed that CIRP and matrix metalloproteinases were highly expressed in OA chondrocytes, whereas collagen Ⅱ exhibited low expression levels. Additionally, CIRP was found to be secreted by OA human chondrocytes in the form of exosomes. CIRP treatment influenced inflammatory related signaling pathway, which in turn affected inflammatory response and extracellular matrix (ECM) degradation in human chondrocytes. Additionally, CIRP induced the nuclear translocation of p65 and promoted ECM degradation dependent the Toll‑like receptor 4 (TLR4)/NF‑κB signaling. The present study also reported that CIRP increased the IL‑1β secretion via the NLR family pyrin domain containing 3 (NLRP3) inflammasome. Furthermore, targeting of CIRP by microRNA‑145 or exosome loading with microRNA‑145 attenuated its role in promoting OA both in vitro and in vivo. The findings indicated that CIRP acts as a pro‑inflammatory factor and activates the TLR4/NF‑κB/NLRP3 pathway, which promotes the inflammatory response, ECM degradation and the progression of OA and targeting CIRP could be a novel strategy for OA treatment.

During antiviral immunity, MHC‑I molecules display endogenous peptides to CD8⁺ T‑cell receptors, prompting cytotoxic elimination of infected cells. The present study focused on dominant epitopes derived from the nucleocapsid protein (NP) of Hantaan virus (HTNV) and revealed their high affinity for the HLA‑I and H‑2 superfamilies. Through immunogenicity and conservation analyses, four selective epitopes were precisely identified. Molecular docking validated the binding characteristics of selective epitopes with MHC‑I molecules. Bidirectional hierarchical clustering analysis uncovered complex interaction patterns between NP 9‑mer peptides and MHC‑I haplotypes. Moreover, in‑depth investigation of 11 HTNV variants revealed three amino acid substitutions (I241S, E242A and F384I) within the four selective epitopes; however, these substitutions did not significantly affect the pan‑HLA‑I immunoreactivity of these epitopes. Safety assessments highlighted the potential of four selective epitopes for practical applications. Utilizing ELISpot, ELISA and flow cytometry, the immunogenicity of these selective epitopes was comprehensively confirmed. In summary, the present study thoroughly evaluated the pan‑MHC‑I immunoreactivity of HTNV NP, providing a robust foundation for developing effective epitope vaccines for population immunity.

Cardiovascular diseases (CVDs) are the leading cause of mortality worldwide and their pathological mechanisms have remained a major focus of research. Notably, copper has an essential role in maintaining cardiovascular homeostasis and disruption of copper metabolism can lead to a range of pathological consequences. The present review summarizes the dynamic balance of copper metabolism, clarifies its regulatory network encompassing intestinal absorption, intracellular transport, tissue storage and excretion, and emphasizes the molecular associations between copper dyshomeostasis and CVDs, including atherosclerosis and stroke. Notably, cuproptosis, a newly identified mode of regulated cell death, provides novel insights into the role of copper‑induced cell death in the cardiovascular system. Based on current research progress, the current review also discusses the value of therapeutics that target copper metabolism, such as copper chelators, ionophores and dietary interventions. Furthermore, key unanswered questions are identified, particularly those regarding the specific molecular pathways linking copper homeostasis to cardiovascular function.

The regulation of methylation and non‑coding RNAs plays important roles in the pathogenesis of osteoporosis. Most microRNAs (miRNAs or miRs) exert their biological functions through target genes. Long non‑coding RNAs function as competing endogenous RNAs. hFOB 1.19 cells were transfected with miR‑4765, LINC00312 and METTL3‑related molecules. LINC00312 and miR‑4765 expression was detected by PCR, whereas cleaved caspase 3 and FOXK2/SFRP1 levels were detected by western blotting. Micro‑computed tomography was used to detect the bone microstructure. Diabetic mice received treatments targeting METTL3 and LINC00312. FOXK2/SFRP1 expression was detected using PCR and immunohistochemistry. The results showed that miR‑4765 overexpression reduced FOXK2/SFRP1 and cleaved caspase 3 expression, causing cell apoptosis. LINC00312 inhibition was observed both in vitro and in vivo. LINC00312 binds directly to miR‑4765, whereas miR‑4765 binds directly to FOXK2/SFRP1. METTL3 and YTHDF2 directly bind LINC00312 and reduce its expression by altering its methylation levels. In conclusion, LINC00312 promotes the apoptosis of hFOB 1.19 cells by targeting the miR‑4765/FOXK2/SFRP1 axis, and METTL3 regulates LINC00312 expression in a YTHDF2‑dependent manner.

The present study investigates the molecular mechanisms of peripheral nerve regeneration by examining the ROCK/PI3K/Akt/GSK3β pathway's role in promoting morphological and functional recovery after peripheral nerve injury (PNI). Using a mouse sciatic nerve crush (SNC) injury model and a dorsal root ganglion (DRG) explant axotomy model, mice and DRG were divided the experimental (treated with DMSO) group, Y27632 group (treated with ROCK inhibitor Y27632), Y + LY group (treated with Y27632 + PI3K inhibitor LY294002), and Y + LY + SB group (treated with Y27632 + LY294002 + GSK3β inhibitor SB216763). Immunofluorescence was used to assess axon density, diameter, myelin thickness and Schwann cell proliferation, while retrograde tracing with cholera toxin subunit B evaluated peripheral‑to‑central reconnection. Behavioral tests measured functional recovery, and in DRG explants, axon regeneration length and growth cone size were quantified. Protein expression analysis of RhoA, ROCK, PI3K, Akt, GSK3β, and their phosphorylated forms was conducted on day 3 post‑axotomy, both in vivo and in vitro. Additionally, RSC96 Schwann cell migration and proliferation were evaluated using scratch assays and EdU staining. Results showed that ROCK inhibition with Y27632 significantly enhanced axonal regeneration, growth cone expansion, retrograde transport, and reinnervation of acetylcholine receptors and Merkel cells, and promoted Schwann cell proliferation and RSC96 migration, leading to thicker myelin sheaths after SNC. These changes mitigated gastrocnemius muscle atrophy, improved muscle strength, gait, and thermal/tactile sensitivity. Co‑treatment with LY294002 blocked these effects, but adding SB216763 restored them. Protein analysis indicated that ROCK inhibition increased phosphorylated PI3K, Akt and GSK3β, whereas PI3K inhibition reduced GSK3β phosphorylation. These findings suggested that ROCK inhibition promotes axon regeneration and remyelination after PNI by enhancing PI3K/Akt phosphorylation and suppressing GSK3β activity, highlighting the therapeutic potential of targeting the ROCK/PI3K/Akt/GSK3β pathway for peripheral nerve repair.

Following the publication of this paper, a concerned reader drew to the Editor's attention that, regarding the western blots shown in Fig. 1A, where the expression levels of salt‑inducible kinase 1 were detected in ovarian cancer tissues, the β‑actin loading controls for patients 4, 6 and 7 were strikingly similar in appearance [also note that, in view of having not received a timely response to this query from the authors, an Expression of concern (DOI: 10.3892/ijmm.2025.5627) was published for this paper]. Moreover, several of the protein bands in this figure were strikingly similar to data which subsequently appeared in another paper written by different authors at different research institutes that was also published in the journal Experimental and Therapeutic Medicine, although this paper has since been retracted. The authors have subsequently replied to say that they are unable to retrieve a portion of the original experimental data, and therefore wish to retract this paper. All the authors agree with the retraction of this article. Both the authors and the Editor of International Journal of Molecular Medicine apologize to the readership for any inconvenience caused. [International Journal of Molecular Medicine 37: 1601‑1610, 2016; DOI: 10.3892/ijmm.2016.2553].

Diabetic nephropathy (DN) and diabetic osteoporosis (DOP) are frequent and debilitating complications of diabetes mellitus (DM), sharing pathological features such as oxidative stress, inflammation and metabolic dysregulation. However, current therapies rarely address these comorbidities simultaneously. In the present study, a type 2 DM rat model presenting both DN and DOP characteristics was established. Rats were treated with Akebia saponin D (ASD), Semaglutide, or their combination. Renal function, calcium‑phosphate metabolism, bone microarchitecture and mechanical properties were evaluated. Network pharmacology, molecular docking and knockdown validation were employed to elucidate underlying mechanisms. Combination therapy markedly improved glomerular structure, decreased fibrosis, restored trabecular bone volume and strength and corrected metabolic imbalance more effectively than monotherapy. Bioinformatic analysis identified the Klotho‑p53 signaling axis as a potential target. ASD exhibited high binding affinity to Klotho in silico and adeno‑associated virus‑mediated Klotho knockdown reversed therapeutic benefits, confirming its pivotal role. ASD and Semaglutide synergistically alleviated both DN and DOP by modulating the Klotho‑p53 axis, offering a promising strategy for comprehensive DM complication management.

Hepatocellular carcinoma (HCC) is among the most common and lethal cancers worldwide and is characterized by complex metabolic and immunological processes throughout its progression. Emerging research has underscored the critical involvement of the gut microbiota and its metabolites, particularly short‑chain fatty acids (SCFAs), in regulating the hepatic immune microenvironment and contributing to the development of HCC. SCFAs play essential roles in the gut‑liver axis by supporting immune homeostasis, modulating lipid metabolism and influencing immune escape mechanisms within the liver. SCFAs are not only products of gut microbiota metabolism but also key regulators of liver metabolism and immune responses. SCFAs play both positive and negative roles in HCC. SCFAs influence T‑cell function and immune responses through the activation of G‑protein‑coupled receptors and the inhibition of histone deacetylases. The present review provided an overview of the current knowledge concerning the regulatory dual effects of SCFAs on the immune microenvironment of HCC, examines their interactions with immune cells via the gut‑liver axis and evaluated their potential as adjuncts in HCC immunotherapy, with the goal of informing future therapeutic strategies.