International journal of molecular medicine最新文献

G protein‑coupled receptor 124 (GPR124) and peroxisome proliferator‑activated receptor γ (PPARγ) constitute two mechanistically distinct signaling molecules that exhibit functional convergence through their opposing regulation of the canonical Wnt/β‑catenin pathway, thereby establishing a critical regulatory network governing inflammatory homeostasis and tissue repair responses. The present comprehensive review elucidates the molecular architecture and pathophysiological significance of the GPR124‑Wnt‑PPARγ regulatory axis, with particular emphasis on its therapeutic implications in chronic inflammatory diseases. GPR124, originally identified as an adhesion G protein‑coupled receptor essential for central nervous system angiogenesis and blood‑brain barrier integrity, functions as a context‑dependent co‑activator of Wnt7a/Wnt7b signaling. By contrast, PPARγ, a ligand‑activated nuclear receptor and master regulator of metabolism and inflammation, exerts potent antagonistic effects on Wnt/β‑catenin signaling through direct β‑catenin degradation mechanisms. The opposing regulation of Wnt signaling by these two receptors establishes a molecular framework that critically influences disease progression in atherosclerosis, diabetic complications, neuroinflammation and cancer‑associated inflammation, with its function being fine‑tuned by tissue‑specific expression patterns and diverse mechanisms. Understanding the GPR124‑Wnt‑PPARγ axis provides novel therapeutic opportunities for combination targeting strategies in chronic inflammatory conditions, where the balance between pro‑angiogenic Wnt activation and anti‑inflammatory PPARγ signaling determines disease outcomes. The present review examines the molecular architecture of GPR124‑PPARγ crosstalk, analyzes pathophysiological implications across multiple organ systems, and evaluates emerging therapeutic strategies for targeting this regulatory network in chronic inflammatory diseases.

Air pollution, an emerging global environmental issue, alongside extreme meteorological conditions exacerbated by climate change, threaten the sustainability of modern society and contribute to the onset and progression of various ear and nose diseases. Nonetheless, the impact of these environmental factors on ear and nose diseases and related dysfunctions remain inadequately explored. The present review involved a comprehensive search of PubMed, Web of Science, the Cochrane Library and Embase for relevant epidemiological and experimental data. How environmental factors contribute to olfactory and auditory system dysfunctions as well as the potential underlying mechanisms from the perspectives of immunity and inflammation were examined in the present review. It was found that air pollution and meteorological factors significantly influence the prevalence of major ear and nose diseases, including allergic rhinitis, otitis media and sudden sensorineural hearing loss. Of note, the present review also provides an examination of the interaction between severe acute respiratory syndrome coronavirus 2 and environmental factors in ear and nose diseases, highlighting how environmental stressors may worsen disease progression. In conclusion, the present review underscores the burden of multimorbidity caused by air pollution and extreme weather and emphasizes the need for more targeted prevention and management strategies for ear and nose diseases.

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by marked genetic heterogeneity and diverse environmental influences. Current treatment approaches focus on symptom management, with only a limited number of effective interventions targeting the underlying causes. Recently, mesenchymal stem cells (MSCs) and their derived exosomes (MSC‑Exos) have emerged as promising candidates for ASD therapy owing to their potent immunomodulatory, neuroprotective and targeted delivery properties. The present review discusses the functions of MSC‑Exos and their potential use in ASD. MSC‑Exos improve neuroinflammation, enhance synaptic plasticity and restore neural network function by delivering bioactive molecules. Moreover, MSC‑Exos exhibit a low immunogenicity, a favorable safety profile and scalability for clinical production. Despite promising results however, clinical trials continue to face challenges, particularly in standardizing the isolation, characterization, dosing and administration routes of exosomes. In addition, significant challenges persist in production processes, quality control and the elucidation of the mechanisms of action. In conclusion, MSC‑Exos represent a groundbreaking, cell‑free therapeutic strategy with substantial potential to target the core pathophysiology of ASD. In the future, multicenter randomized controlled trials and interdisciplinary collaborations will be crucial for translating preclinical findings into the development of effective and transformative therapies for ASD. 

In cells, copper levels are tightly regulated because copper deficiency leads to Menkes disease, anemia and neurodegeneration, whereas copper overload is associated with Wilson disease, liver injury, neurodegeneration and several cancers. Cuproptosis, a form of regulated cell death, depends on the intracellular accumulation of excessive copper. This process induces mitochondrial dysfunction and cell death by disrupting the stability of mitochondrial lipoylated proteins and iron‑sulfur cluster proteins. The present review aimed to summarize the mechanisms underlying cuproptosis in gastrointestinal cancer, with a focus on the relationship between copper metabolism imbalance and tumor initiation and progression, as well as the potential therapeutic applications of cuproptosis‑associated agents in oncology. The application prospects of cuproptosis in gastrointestinal tumor therapy are broad, offering novel therapeutic options that may improve prognosis in patients and survival outcomes.

Following the publication of this article, a concerned reader drew to the Editor's attention that the image showing silica nanoparticles in Fig. 1 on p. 906 had also been used to show the same data in another paper published by the same research group in International Journal of Molecular Medicine. Upon performing a separate investigation of the data in this paper in the Editorial Office, it also came to light that flow cytometric plots featured in Fig. 3 on p. 908 had originally been included in a paper featuring some of the same authors that had already been published in International Journal of Nanomedicine, and western blot data featured in Fig. 7 on p. 910 were originally included in another paper featuring some of the same authors in the journal Stem Cell Research & Therapy. Given the apparent re‑use of the abovementioned data in this article from previously published papers, the Editor of International Journal of Molecular Medicine has decided that this article 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 44: 903‑912, 2019; DOI: 10.3892/ijmm.2019.4265]

Following the publication of this article, a concerned reader drew to the Editor's attention that the image showing silica nanoparticles in Fig. 1 on p. 1232 had also been used to show the same data in another paper published by the same research group in International Journal of Molecular Medicine. Upon performing a separate investigation of the data in this paper in the Editorial Office, it also came to light that, concerning the immunohistochemical images shown in Fig. 8A on p. 1236, five pairs of data panels out of a total of 12 panels included in this figure contained overlapping sections of data, occasionally in different orientations with respect to other panels, such that data which were intended to show the results from differently performed experiments had apparently been derived from a smaller number of original sources. Given the large number of panels in this figure that were revealed to have overlapping sections, the Editor of International Journal of Molecular Medicine has decided that this article 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 43: 1229‑1240, 2019; DOI: 10.3892/ijmm.2018.4045].

Cognitive impairment remains an important global health concern, with the molecular mechanisms regulating its progression being a primary research focus. Ferroptosis, a unique form of programmed cell death characterized by iron‑dependent lipid peroxidation, has been increasingly recognized for its essential role in the progression of various neurodegenerative diseases and diabetes‑associated cognitive impairment. The present review summarizes current evidence on how ferroptosis contributes to cognitive decline and outlines its regulation through lipid, iron and glutathione metabolism; it further discusses how diverse upstream pathologies converge on ferroptosis as a shared mechanism underlying cognitive dysfunction. In addition, recent advances in ferroptosis‑related biomarkers and therapeutic strategies are highlighted, with the aim of providing a clearer framework for understanding its pathogenic roles and guiding future clinical translation.

Hepatic stellate cells (HSCs), specialized liver‑resident pericytes, play pivotal roles in both liver fibrogenesis and regeneration. Following hepatic injury, quiescent HSCs undergo activation and transdifferentiation into myofibroblasts, which drive tissue remodeling and scar formation. Recent advances have uncovered notable phenotypic and functional heterogeneity within HSC populations, with distinct subsets displaying context‑dependent activation states and specialized functions across diverse liver pathologies. The present review synthesizes current insights into the dynamic spectrum of HSC phenotypes and the molecular mechanisms governing their plasticity, emphasizing the mechanisms through which niche‑specific signaling, epigenetic regulation and metabolic reprogramming coordinate their functional diversity. The present review further discuss emerging therapeutic strategies that leverage this heterogeneity to selectively target pathogenic HSC subsets, while preserving their homeostatic roles, thereby opening new avenues for precision anti‑fibrotic therapies and liver regeneration.

Zymogen granule protein 16B (ZG16B), also known as pancreatic adenocarcinoma upregulated factor, is a secretory lectin‑like glycoprotein that serves a crucial role in tumorigenesis and immune regulation. The present review summarizes the latest research progress on the molecular characteristics, biological functions, signaling pathway regulation and clinical importance of ZG16B. Structurally, ZG16B contains an N‑terminal hydrophobic signal peptide, a jacalin‑related lectin domain and a C‑terminal extension. Functionally, ZG16B promotes tumor cell proliferation, migration, invasion and angiogenesis, and increases vascular permeability by activating the Toll‑like receptor, C‑X‑C chemokine receptor type 4, β‑catenin and focal adhesion kinase signaling pathways. In the tumor microenvironment, ZG16B can modulate immune responses, enhance the immunosuppressive functions of myeloid‑derived suppressor cells and M2 macrophages, and also promote the maturation of dendritic cells. Clinically, ZG16B expression is upregulated in pancreatic cancer, ovarian cancer, colorectal cancer, gastric cancer and oral cancer, and its upregulation is associated with a worse prognosis in these malignancies. Several ZG16B‑specific therapeutic strategies, including monoclonal antibodies, RNA aptamers and trans‑splicing ribozymes, have shown preclinical efficacy against malignant tumors. Furthermore, a clinical trial is currently testing the efficacy and safety of PBP1510, a humanized ZG16B antibody, for the treatment of advanced pancreatic cancer. In conclusion, ZG16B may be considered a novel target for cancer diagnosis, prognosis and therapy.

X‑linked retinitis pigmentosa, primarily caused by mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene, represents one of the most severe forms of inherited retinal degeneration, with early onset and rapid progression. Conventional interventions, such as vitamin A or docosahexaenoic acid supplementation, offer limited benefits and fail to halt disease progression. By contrast, gene therapy has emerged as a promising approach to alter the disease course. The present review summarizes the clinical phenotypes and pathogenic mechanisms associated with RPGR mutations, focusing on their disruption of ciliary transport and metabolic homeostasis. The present review further discusses advances in preclinical models, including mice, dogs, zebrafish and induced pluripotent stem cell‑derived organoids, that have facilitated the development of RPGR‑targeted therapies. Adeno‑associated virus‑based gene replacement has shown efficacy in restoring retinal structure and function, and several approaches have progressed to early‑phase clinical trials. Despite encouraging outcomes, challenges such as RPGR coding sequence instability, vector delivery efficiency and long‑term safety remain. The present review integrates current mechanistic understanding and therapeutic progress, providing a translational perspective for precision treatment of RPGR‑associated retinal diseases.