International Journal Of Molecular Medicine[JOURNAL]
Sun
200 papers
Natural products as multi‑target therapies for sepsis‑induced myocardial dysfunction (Review).
Tang F, Liu D, Zhu SC … +2 more , Zhou HM, Qiu XW
Int J Mol Med · 2026 Mar · PMID 41574690 · Full text
Sepsis, an infection‑triggered systemic inflammatory response syndrome, ranks as the third leading cause of death worldwide due to its high incidence and mortality. Sepsis‑induced myocardial dysfunction (SIMD) is a frequ...
Sepsis, an infection‑triggered systemic inflammatory response syndrome, ranks as the third leading cause of death worldwide due to its high incidence and mortality. Sepsis‑induced myocardial dysfunction (SIMD) is a frequent and serious complication that notably increases patient morbidity and mortality. The underlying pathophysiology of SIMD involves a complex interplay of inflammation, oxidative stress, mitochondrial impairment and apoptosis, yet no effective therapies have been established. Thus, uncovering the molecular mechanisms of SIMD, identifying novel therapeutic targets and developing efficacious agents are key. For centuries, natural products have been used in traditional medical systems across China and Asia to manage cardiovascular disease. These compounds can confer cardioprotection by modulating inflammatory pathways, decreasing oxidative stress, inhibiting apoptotic cell death and improving mitochondrial function. The present review aimed to summarize the clinical manifestations and pathophysiology of SIMD and how natural products exert their protective effects. The present study aimed to explore structure‑activity relationships and highlight key molecular targets and representative natural product binding affinities for SIMD‑related proteins. In summary, the present study presents a comprehensive overview of the multi‑targeted strategies employed by natural products against SIMD and provides guidance for the discovery of SIMD‑focused dietary supplements and lead compounds, laying the groundwork for future translational research.
ZG16B: A key regulator of tumor progression and immune microenvironment modulation in cancer (Review).
Chen XM, Liang YB, Zuo JX … +5 more , Yang ZS, Zhang LY, Zhang XY, Wan P, Ke Y
Int J Mol Med · 2026 Mar · PMID 41543187 · Full text
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 revi...
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.
<p>Harnessing MSC‑derived exosomes to modulate the pathophysiology of ASD: Recent advances and therapeutic implications (Review)</p>.
Sun Z, Amjad N, Muhammad M … +1 more , Li Z
Int J Mol Med · 2026 Mar · PMID 41543180 · Full text
<p>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, wi...
<p>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. </p>.
<p>Beyond hepatic stellate cell heterogeneity: Resolving fibrosis, restoring regeneration (Review)</p>.
Gao C, Chen G, Jia H … +4 more , Zhu H, Cai Y, Yang D, Zhao K
Int J Mol Med · 2026 Mar · PMID 41543176 · Full text
<p>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...
<p>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.</p>.
[Corrigendum] CDKN2A (p16INK4A) affects the anti‑tumor effect of CDK inhibitor in somatotroph adenomas.
Chen Y, Li Z, Fang Q … +4 more , Wang H, Li C, Gao H, Zhang Y
Int J Mol Med · 2026 Mar · PMID 41543159 · Full text
<p>Following the publication of the above article and an expression of concern statement (doi: 10.3892/ijmm.2025.5680) after it had been drawn to the Editor's attention by an interested reader that, regarding the western...
<p>Following the publication of the above article and an expression of concern statement (doi: 10.3892/ijmm.2025.5680) after it had been 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, the authors have now replied to the Editorial Office to explain the apparently anomalous appearance of this figure. After having examined their original data, the authors have realized that this figure was assembled incorrectly; essentially, the wrong data were included in this figure to portray the GAPDH bands for the GH3 cell line. The revised version of Fig. 5, now showing the correct GAPDH data for the GH3 cell line, is featured on the next page. The authors can confirm that the error made during the assembly of Fig. 5 did not have a 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 47: 500‑510, 2021; DOI: 10.3892/ijmm.2020.4807]</p>.
[Retracted] Mechanism of cell death induced by silica nanoparticles in hepatocyte cells is by apoptosis.
Yang Y, Du X, Wang Q … +9 more , Liu J, Zhang E, Sai L, Peng C, Lavin MF, Yeo AJ, Yang X, Shao H, Du Z
Int J Mol Med · 2026 Mar · PMID 41543149 · Full text
<p>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 pu...
<p>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 . 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 , 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 . Given the apparent re‑use of the abovementioned data in this article from previously published papers, the Editor of 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]</p>.
[Retracted] Silica nanoparticles induce cardiomyocyte apoptosis via the mitochondrial pathway in rats following intratracheal instillation.
Du Z, Chen S, Cui G … +12 more , Yang Y, Zhang E, Wang Q, Lavin MF, Yeo AJ, Bo C, Zhang Y, Li C, Liu X, Yang X, Peng C, Shao H
Int J Mol Med · 2026 Mar · PMID 41508938 · Full text
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 publ...
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 . 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 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].
Role and mechanisms of ferroptosis in cognitive impairment: From molecular pathways to therapeutic targets (Review).
Ge S, Kong D, Fan S … +5 more , Luo Y, Yin X, Jin Z, Xia W, Ma J
Int J Mol Med · 2026 Mar · PMID 41480709 · Full text
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...
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.
The GPR124‑Wnt‑PPARγ regulatory axis: Molecular mechanisms and therapeutic implications in chronic inflammatory diseases (Review).
Cui MW, Tao SY, Wen T … +1 more , Guo ZL
Int J Mol Med · 2026 Mar · PMID 41480707 · Full text
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 regu...
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.
Environmental exposure to air pollution and climate: Intersecting the impact on ear and nose health and chemosensory function (Review).
Zhang YC, Zhang L, Zhou PT … +6 more , Xie ZH, Zhang WJ, Fan M, Han YX, Liu YH, Liu YC
Int J Mol Med · 2026 Mar · PMID 41480694 · Full text
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...
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.
Role of cuproptosis in digestive system tumors (Review).
Zhang L, Cheng Y, Tang L … +2 more , Zhu J, Tuo B
Int J Mol Med · 2026 Mar · PMID 41480689 · Full text
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 an...
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.
Advances in RPGR gene therapy for X‑linked retinitis pigmentosa: From preclinical insights to clinical application (Review).
Long Y, Qi J, Zhang W … +2 more , Qin H, Yao K
Int J Mol Med · 2026 Mar · PMID 41480687 · Full text
X‑linked retinitis pigmentosa, primarily caused by mutations in the () gene, represents one of the most severe forms of inherited retinal degeneration, with early onset and rapid progression. Conventional interventions...
X‑linked retinitis pigmentosa, primarily caused by mutations in the () 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 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 ‑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 ‑associated retinal diseases.
miR‑205: A dual regulator of angiogenesis in health and disease (Review).
Oltra M, Martínez-Santos M, Ybarra M … +6 more , Pires M, Ceresoni C, Gomis-Coloma C, Medina-Trillo C, Sancho J, Barcia J
Int J Mol Med · 2026 Feb · PMID 41480686 · Full text
The present study evaluated the role of microRNA (miR)‑205 as a dual regulator of angiogenesis, exhibiting both pro‑angiogenic and anti‑angiogenic effects depending on the biological context. miRs are small non‑coding se...
The present study evaluated the role of microRNA (miR)‑205 as a dual regulator of angiogenesis, exhibiting both pro‑angiogenic and anti‑angiogenic effects depending on the biological context. miRs are small non‑coding sequences that regulate gene expression at the post‑transcriptional level and can be transported in extracellular vesicles (EVs), allowing them to modulate biological processes remotely. miR‑205 is involved in multiple cellular processes, such as proliferation, migration, apoptosis and angiogenesis. In angiogenesis its function is contradictory: On one hand, it can inhibit blood vessel formation by suppressing pro‑angiogenic factors such as VEGF and ANG‑2, as demonstrated in diseases such as psoriasis, thyroid cancer and diabetic retinopathy. However, in other contexts, miR‑205 promotes angiogenesis by inhibiting anti‑angiogenic genes such as and , facilitating the activation of the PI3K/AKT pathway and cell proliferation in ovarian cancer and thrombosis. Additionally, the present study highlighted the role of EVs in transferring miR‑205 between cells, thereby influencing angiogenesis and disease progression. Studies in myocardial infarction and cancer models have demonstrated that EVs enriched in miR‑205 can affect blood vessel formation and tumor progression. Similarly, in ocular diseases such as macular degeneration and diabetic retinopathy, miR‑205 encapsulated in EVs has shown therapeutic potential by regulating VEGF levels. In conclusion, miR‑205 emerges as a promising therapeutic target for angiogenic diseases. Its application in EV‑based therapy could represent an innovative strategy for treating vascular disorders. However, further studies are needed to fully understand its mechanisms of action and optimize its clinical application.
Role of SIRT3 in digestive system diseases and therapeutic prospects (Review).
Li J, Liu Q, Yao S … +7 more , Li X, Zhang L, Wang Y, Wen G, An J, Jin H, Tuo B
Int J Mol Med · 2026 Feb · PMID 41456501 · Full text
The family of silent information regulators (sirtuins) constitutes a highly conserved protein family that exhibits two primary enzymatic activities : NAD‑dependent protein deacetylase activity and adenosine diphosphate‑r...
The family of silent information regulators (sirtuins) constitutes a highly conserved protein family that exhibits two primary enzymatic activities : NAD‑dependent protein deacetylase activity and adenosine diphosphate‑ribose transferase activity. Sirtuin 3 (SIRT3), a member of the sirtuin family, is widely expressed in mitochondria‑rich tissues such as the brain, heart, liver and kidney, and functions primarily as a deacetylase. The deacetylations regulated by SIRT3 modulate various metabolic substances and processes within the mitochondrial matrix, playing a crucial role in maintaining normal digestive system function. Therefore, this review focuses on the role of SIRT3 in digestive system diseases to elucidate its function in pathogenic signaling pathways and explore the development of drug targets targeting SIRT3 and related disease pathways, offering new directions for improving the treatment of digestive system‑related diseases.
Activating transcription factors: Orchestrators of macrophage biology in pathological settings (Review).
Liu YC, Zhao JW, Yue XT … +6 more , Chen QJ, Rong SJ, Liu SW, Sun F, Yang CL, Wang CY
Int J Mol Med · 2026 Feb · PMID 41456500 · Full text
Macrophages, an essential component of the innate immune system, exhibit remarkable plasticity and functional heterogeneity governed by the intricate transcriptional regulatory networks. Activating transcription factors...
Macrophages, an essential component of the innate immune system, exhibit remarkable plasticity and functional heterogeneity governed by the intricate transcriptional regulatory networks. Activating transcription factors (ATFs) have recently been recognized to modulate multiple signaling pathways, including the MAPK cascades, endoplasmic reticulum stress response and NF‑κB signaling, thereby regulating macrophage biological processes such as inflammatory response, glucose‑lipid metabolism, cellular stress adaptation, autophagy‑apoptosis balance and senescence. By integrating stress signals and metabolic cues, ATF family members construct a sophisticated regulatory network implicated in the pathogenesis of infectious and inflammatory diseases, metabolic disorders, malignancies and neurodegenerative diseases. Therefore, targeted modulations of ATFs or their associated pathways are considered to be capable of precisely regulating macrophage anti‑inflammatory function, metabolic activity and tissue repair capacity in disease settings. Recent technological advances, such as specific targeted delivery systems and gene‑editing strategies, offer promising avenues for the spatiotemporal ATF‑targeting interventions in macrophages, which is critical for improving therapeutic efficacy and safety. The present review systematically summarized recent advances in the understanding of ATF‑mediated regulation of macrophage development, survival, migration, phagocytosis, activation/cytokine secretion, along with polarization and metabolic reprogramming. It also elucidated the pathophysiological implications of these regulatory mechanisms and critically evaluated the clinical feasibility of ATF‑targeted therapeutic interventions.
Astragaloside IV: A multipotent phytochemical for treating fibrotic diseases (Review).
Wu M, Li K, Wu J … +7 more , Zhang Q, Ma X, Dai W, Gao H, Ding X, Wang W, Xiao W
Int J Mol Med · 2026 Feb · PMID 41456499 · Full text
Fibrosis is a maladaptive response of tissues or organs to adverse stresses, such as chronic inflammation, infection and mechanical injury. It further promotes parenchymal cell loss, abnormal myofibroblast proliferation...
Fibrosis is a maladaptive response of tissues or organs to adverse stresses, such as chronic inflammation, infection and mechanical injury. It further promotes parenchymal cell loss, abnormal myofibroblast proliferation and excessive extracellular matrix buildup, eventually triggering scar tissue hyperplasia or organ injury. Although a moderate fibrotic response is beneficial for compensatory tissue repair induced by exogenous or endogenous injury, excessive fibrosis is the basis for the promotion of multiorgan pathologies, such as cardiac hypertrophy, idiopathic pulmonary fibrosis, or renal tubulointerstitial fibrosis. In industrialized countries alone, fibrotic diseases account for ~45% of all‑cause mortality. Consequently, the development of medications that regulate the activation of growth factors, proliferation of fibrotic effector cells and deposition and degradation of the extracellular matrix is essential. Botanical compounds derived from Chinese medicine are generally considered natural tonics. Among these compounds, astragaloside IV (AS‑IV) is a bioactive product isolated from the roots of Bunge. On the basis of the multitarget therapeutic mechanism of Chinese herbal medicine, AS‑IV may have considerable benefits in improving multiorgan fibrosis and complex fibrotic diseases with multisignal cascades. It can effectively alleviate the fibrosis‑induced dysfunction of major tissues or organs, including the heart, lungs, kidneys and liver, by regulating the signal transduction of reactive oxygen species/caspase‑1/gasdermin D, transforming growth factor‑β/Smads, Wnt/β‑catenin and sirtuin 1‑nuclear factor‑κ B. The present review mainly focused on phytomedicine and highlights the potential of AS‑IV as an antifibrotic medication. It aimed to provide a novel reference for the application of AS‑IV in the nutritional intervention of fibrotic diseases.
Recombinant ADAMTS‑1 promotes muscle regeneration accompanied by downregulation of Notch signaling.
Kim JH, Lee SH, Kim SY … +8 more , Kim JW, Jeong JS, Chung EH, Lee SH, Kim CY, Choi BK, Ko JW, Kim TW
Int J Mol Med · 2026 Feb · PMID 41456440 · Full text
Skeletal muscle satellite cells (MuSCs) play a central role in muscle regeneration; however, their capacity declines with age, contributing to sarcopenia. A disintegrin and metalloproteinase with thrombospondin motifs‑1...
Skeletal muscle satellite cells (MuSCs) play a central role in muscle regeneration; however, their capacity declines with age, contributing to sarcopenia. A disintegrin and metalloproteinase with thrombospondin motifs‑1 (ADAMTS‑1) regulates MuSC activation and differentiation. The present study aimed to investigate the potential of recombinant ADAMTS‑1 (rADAMTS‑1) as a therapeutic strategy to enhance MuSC proliferation and improve regeneration. After barium chloride injection, mice received daily intraperitoneal injections of rADAMTS‑1 at 5 or 10 mg/kg for 1, 3, 7, or 14 days to monitor recovery. Primary skeletal muscle and C2C12 cells were also treated with rADAMTS‑1 to evaluate its effects on gene and protein expression during proliferation and differentiation . The number of MuSCs and the expression of myogenic markers increased in all injured groups by day 3 post‑injury . These levels were particularly elevated in the high‑dose rADAMTS‑1 group and remained sustained until day 14. Grip strength recovered to normal levels by day 7 in the high‑dose rADAMTS‑1 group, suggesting improved functional recovery compared with the untreated controls. In vitro, rADAMTS‑1 treatment induced a dose‑dependent increase in muscle fiber length and upregulation of regeneration‑related factors in primary skeletal muscle cells. Furthermore, C2C12 cells treated with rADAMTS‑1 exhibited enhanced expression of myocyte developmental genes during differentiation. The findings highlighted the therapeutic potential of rADAMTS‑1 for sarcopenia, potentially addressing limitations associated with conventional MuSC‑based treatments.
A comprehensive review on pain: Model, target, therapy, and prospect (Review).
Chang C, Wu X, Liu K … +8 more , Wang L, Adu M, Lin Q, Huang H, Ma Q, Wei R, Wang X, Liu W
Int J Mol Med · 2026 Feb · PMID 41416447 · Full text
Pain serves as both a protective physiological response essential for species survival and a global health issue affecting human well‑being and societal development. The present review systematically summarized and analy...
Pain serves as both a protective physiological response essential for species survival and a global health issue affecting human well‑being and societal development. The present review systematically summarized and analyzed the research progresses on pain through a multidimensional analytical framework encompassing animal models, molecular targets, therapeutic approaches and future prospects. In animal modeling, neuropathic pain paradigms have evolved from traditional mechanical compression to composite models that combine dynamic displacement and chemical stimulation. Cancer‑induced pain models employ orthotopic tumor transplantation to recapitulate bone metastasis and soft tissue invasion mechanisms and visceral pain models combine inflammatory mediators with mechanical distension to replicate clinical manifestations. The above animal models are the main models of pain, each with its own characteristics and applicable scope. The studies of molecular targets have identified voltage‑gated ion channel, G protein‑coupled receptor signaling cascades, and inflammation‑related enzymes as critical analgesic targets, providing a molecular basis for the design of new analgesic drugs. New targets for treating pain are still being studied. Clinical treatment strategies are showing a trend of multimodal integration, with breakthroughs in opioid optimization and non‑opioid innovation in drug therapy, precise analgesia achieved through neuromodulation techniques in intervention therapy, and strengthened chronic pain management dimensions through physical and psychological interventions. Although there are a number of means for treating pain, the research on drugs that can truly cure pain has still a long way to go. The future research and development of analgesics will focus on in‑depth analysis of pathological mechanisms, adverse reactions of opioid drugs, personalized analgesic strategies, and interdisciplinary transformation.
[Retracted] Curculigoside attenuates myocardial ischemia‑reperfusion injury by inhibiting the opening of the mitochondrial permeability transition pore.
Zhao Y, Guo Y, Chen Y … +3 more , Liu S, Wu N, Jia D
Int J Mol Med · 2026 Feb · PMID 41416433 · Full text
Following the publication of this paper, a concerned reader drew to the Editor's attention that a pair of the fluorescence microscopic images shown in Fig. 2A on p. 1518 were strikingly similar to data which had already...
Following the publication of this paper, a concerned reader drew to the Editor's attention that a pair of the fluorescence microscopic images shown in Fig. 2A on p. 1518 were strikingly similar to data which had already been accepted for publication in the journal written by different authors, although the same department and research institute were held in common. Upon performing an independent analysis of the data in this paper in the Editorial Office, it also came to light that flow cytometric data in Fig. 2B had already been submitted for publication in another paper to the journal Drug Design, Development and Therapy that featured some of the same authors, although the experimental conditions in the two papers were reported to be different. Owing to the fact that the contentious flow cytometric and fluorescence microscopic data in the above article had apparently already been submitted for publication elsewhere, the Editor of 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 satisfactory reply. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Molecular Medicine 45: 1514‑1524, 2020; DOI: 10.3892/ijmm.2020.4513].
Selective autophagic degradation of glycolytic activator PFKFB3 contributes to maintaining intestinal epithelial barrier in inflammatory bowel disease.
Pan Y, Yang F, Wang L … +6 more , Yang T, Du G, Xu C, Yang H, Yu M, Xiao W
Int J Mol Med · 2026 Feb · PMID 41384306 · Full text
Inflammatory bowel disease (IBD) is a chronic idiopathic intestinal inflammatory disease with increasing incidence worldwide. However, the treatment of IBD is still limited and has not reached the expected therapeutic ef...
Inflammatory bowel disease (IBD) is a chronic idiopathic intestinal inflammatory disease with increasing incidence worldwide. However, the treatment of IBD is still limited and has not reached the expected therapeutic effect and new therapeutic targets are still to be discovered. Impaired autophagy and abnormal glycolysis levels were observed both in the and intestinal inflammation models, suggesting a relationship between autophagy and glycolysis in IBD. Subsequently, it demonstrated that autophagy negatively regulated the glycolysis of IECs by degradation of the key glycolytic enzyme 6‑phosphofructo‑2‑kinase/fructose‑2,6‑bisphosphatase 3 (PFKFB3). Co‑immunoprecipitation was employed to demonstrate that PFKFB3 ubiquitinated by fizzy and cell division cycle 20 related 1 E3 ligase and was then recognized by P62 autophagy receptor for degradation. Notably, increased PFKFB3 expression was detected both in patients with CD and DSS‑induced colitis. Inhibiting PFKFB3 enzyme activity relieved DSS‑induced intestinal inflammation and intestinal epithelial barrier damage. The present study proposed a combined therapy targeting autophagy and glycolysis might become a new choice for clinical treatment of IBD.
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