International journal of molecular medicine最新文献

The blood‑retinal barrier (BRB), a critical component of the retinal neurovascular unit (NVU), is essential for maintaining retinal homeostasis. Dysfunction of the BRB contributes to vascular leakage, neuronal degeneration and gliosis, which are the core pathological hallmarks of diabetic retinopathy (DR) and retinal vein occlusion (RVO). Despite the importance of the BRB, the molecular mechanisms underlying the preservation of BRB integrity under pathological conditions remain unclear. The present study identified the endothelial receptor unc‑5 netrin receptor B (UNC5B) as a critical regulator of BRB and NVU homeostasis and a potential therapeutic target for neurovascular protection. Analysis of a public Gene Expression Omnibus single‑cell transcriptomic dataset, cell and animal models, and clinical samples revealed reduced UNC5B expression in the aqueous humor of patients and in the retinas of DR and RVO models. In vitro, endothelial knockdown of UNC5B increased apoptosis (assessed by PI/calcein‑AM staining), impaired barrier function (evaluated by BSA uptake and permeability of cell monolayer) and reduced pericyte recruitment, whereas UNC5B knockdown in pericytes had no detectable effects on pericyte proliferation, apoptosis or migration. In vivo, endothelial‑specific UNC5B deficiency markedly exacerbated retinal vascular leakage and structural damage in the DR model, as evidenced by Evans blue leakage, Periodic acid‑Schiff staining and immunofluorescence analyses. Furthermore, UNC5B knockdown abolished the protective effects of high‑dose netrin‑1 administration in DR mice. Endothelial UNC5B modulation, including knockdown and overexpression, affected not only the vascular integrity but also the neural components within the NVU, as evidenced by altered retinal ganglion cell degeneration and glial activation in the DR model, assessed using NeuN, β‑III tubulin and vimentin staining. In the RVO model, endothelial UNC5B deficiency aggravated retinal edema and thinning, as revealed by in vivo retinal imaging. Mechanistically, transcriptomic and protein analyses revealed that UNC5B downregulation was associated with increased extracellular matrix protein deposition and reduced Hippo pathway activity. Collectively, these findings established UNC5B as a key mediator of BRB and NVU stability, and highlighted its therapeutic potential in maintaining vascular integrity and protecting neural elements in retinal vascular diseases.

Osteoporosis is a metabolic bone disease marked by decreased bone mineral density and deterioration of bone microarchitecture. Its development involves complex interactions between genetic factors, nutrition, hormones and lifestyle factors. As the global population is aging, osteoporosis has become a public health concern. Although drug treatments such as bisphosphonates and hormone replacement therapy are available, these options are limited by high costs and adverse side effects, highlighting the need for alternative approaches. The gut microbiota is a regulator of bone metabolism through its metabolites, effects on immune function and role in maintaining intestinal barrier integrity, endocrine signaling and nutrient absorption. Exercise, beyond its role in promoting bone strength through mechanical loading, enhances calcium absorption, thereby modulating gut microbiota composition. Within this context, exercise‑based strategies may provide a promising avenue for both osteoporosis prevention and treatment by targeting the gut‑bone axis, however, the underlying molecular mechanisms remain incompletely understood and additional clinical evidence is required. The present review summarizes how exercise‑induced changes in gut microbiota may influence bone health, also discussing the relevance of these to the management of osteoporosis.

Sepsis‑induced vasoplegia, a life‑threatening complication of sepsis, has become a focal point of research endeavors aimed at determining its complex mechanisms. However, existing investigations predominantly focus on the role of endothelial cells (ECs) in sepsis, inadvertently dismissing the pivotal contribution of vascular smooth muscle cells (VSMCs). The present review highlights the frequently underappreciated role of VSMCs in sepsis‑induced vasodilation, and provides a comprehensive and systematic elucidation of the associated pathophysiological mechanisms. The current review examines the structural characteristics, localization, phenotypic transitions and heterogeneity of VSMCs, emphasizing their critical role in maintaining vascular homeostasis and regulating blood pressure. Subsequently, the review delves into the multifaceted effects of sepsis on VSMCs. Direct injury to VSMCs in sepsis occurs through pathogens. Additionally, the sepsis‑associated cytokine storm can activate key signaling pathways, such as the NF‑κB and p38 MAPK pathways, leading to a phenotypic shift in VSMCs from a contractile state to a synthetic state, thus enhancing their proliferative and migratory abilities. Concurrently, sepsis disrupts the intricate interaction between ECs and VSMCs, and interferes with calcium homeostasis, ultimately resulting in reduced vascular reactivity and abnormal vascular remodeling. Together, these mechanisms contribute to sepsis‑related vascular dysfunction and multiorgan failure. The in‑depth analysis of these processes in the present review offers novel insights into the pathological mechanisms of sepsis‑induced vasoplegia. The current study also provides a theoretical foundation for the development of clinical intervention strategies targeting VSMCs, with the potential to advance sepsis treatment strategies.

Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease, with increasing global prevalence, resulting in a notable increase in the risk of kidney failure and cardiovascular events. Post‑translational modifications (PTMs) are biochemical modifications that occur on specific residues on proteins, leading to an increase in the diversity of proteins and modulation of protein functions. PTMs encompass numerous processes, including phosphorylation, acetylation, methylation, ubiquitination, small ubiquitin‑like modifier‑ylation, glycosylation, palmitoylation, glutathionylation, S‑nitrosylation, sulfhydration, as well as lactylation and neddylation. PTMs are associated with the occurrence and progression of DKD. The present review aimed to summarize PTMs and their roles in the pathophysiological mechanisms of DKD, including cell death, oxidative stress, mitochondrial dysfunction, inflammation and fibrosis.

Diabetic cardiomyopathy (DCM) is a significant complication in patients with diabetes, but its pathogenesis is not fully understood. In recent years, dynamic regulation of lipid droplets (LDs) balance has gradually become a new therapeutic direction with great potential. LDs regulate lipid storage, energy supply and interconnected drivers; for instance, oxidative damage, inflammation, autophagy, ferroptosis, affect the function and cellular homeostasis of cardiomyocytes, macrophages and fibroblasts, and thus participate in DCM. The present review discusses the multiple functions of LDs in regulating DCM by affecting cell homeostasis and summarizes the research progress of therapies targeting LDs and related metabolic pathways, which may inform novel strategies for preventing and treating DCM.

Following the publication of the above article, an interested reader drew to the authors' attention that, concerning the Von Kossa staining experiments shown in Fig. 5E on p. 2002, the 'NC' and 'OvercircRNA‑0079201+miR‑140‑3p mimic' data panels appeared to contain an overlapping section of data, such that data which were intended to show the results of different experiments had apparently been derived from the same original source. In addition, it was also noted that the COL10A1 western blots featured in Fig. 5D were strikingly similar to blots that had appeared in an article in Journal of Cellular and Molecular Medicine by the same research group. In their response, the authors confirmed that the only figure part requiring correction was the 'NC' von Kossa staining panel in Fig. 5E; concerning the COL10A1 western blot in Fig. 5D, after re‑examining the original experimental records and source files, they could confirm that this panel was derived from experiments conducted specifically for the above article. The revised version of Fig. 5, now showing the correct data for the 'NC' data panel in Fig. 5E, is shown on the next page. The authors can confirm that the errors 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 46: 1993‑2006, 2020; DOI: 10.3892/ijmm.2020.4737].

Following the publication of the above article, an interested reader drew to the authors' attention that, concerning the Transwell migration assay images shown in Fig. 6 on p. 287, the data panels for figure parts 6E (the DMSO experiment) and 6G (the pcDNA3.1+DMSO experiment) contained strikingly similar data, albeit with different sizing of the images, suggesting that these data had been derived from the same original source. Upon investigating this figure, the authors realized that this figure had inadvertently been assembled incorrectly: The data panel for the DMSO group in the HTR‑8/SVneo cell migration assay (Fig. 6E) had been duplicated from the correctly displayed pcDNA3.1+DMSO group panel. The revised version of Fig. 6, now showing the correct data panel for Fig. 6E, is shown on the next page. 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 44: 281-290, 2019; DOI: 10.3892/ijmm.2019.4175].

Subsequently to the publication of the above paper, an interested reader drew to the authors' attention that, concerning the immunofluorescence images shown in Fig. 2C on p. 855, the 'Blank/E‑cadherin' and 'TGF‑β2‑SIS3/E‑cadherin' data panels appeared to show the same data, albeit with different intensities of staining. In addition, in Fig. 3B on p. 856, the GAPDH blots shown for the '7 days' and '28 days' experiment gels were strikingly similar in appearance, in spite of different experiments being reported. After having asked the authors to explain the apparent anomalies in these figures, they realized that they had been assembled erroneously. Corrected versions of Figs. 2 and 3, now showing the correct data for the 'TGF‑β2‑SIS3/E‑cadherin' experiment in Fig. 2C and the GAPDH western blots for the '28 days' experiment in Fig. 3B, are shown opposite and on the next page. The errors made in assembling Figs. 2 and 3 did not grossly affect either the results or the conclusions reported in this paper. All the authors agree with the publication of this corrigendum, and are grateful to the Editor of International Journal of Molecular Medicine for allowing them the opportunity to present this; moreover, the Editor and the authors apologize to the readership for any inconvenience caused. [International Journal of Molecular Medicine 42: 851‑860, 2018; DOI: 10.3892/ijmm.2018.3662].

Follistatin‑like protein 1 (FSTL1), a secreted glycoprotein, serves a key role in regulating various biological processes. The present review explores the molecular mechanisms through which FSTL1 influences inflammation, cellular senescence and tumour progression. As a multifunctional protein with both autocrine and paracrine properties, FSTL1 regulates cell survival, proliferation, differentiation and migration, while also modulating immune responses. Evidence indicates that FSTL1 exerts context‑dependent regulatory effects on pathological conditions by modulating signalling pathways, such as TGF‑β, NF‑κB and MAPK. Furthermore, increased FSTL1 expression has been found in the inflammatory synovial tissues of patients with osteoarthritis and it contributes to nucleus pulposus cell inflammation. In conclusion, the distinctive structural features and widespread expression of FSTL1 position it as a key target for understanding the mechanisms underlying inflammation, senescence and tumourigenesis, providing potential options for novel diagnostic and therapeutic strategies for these conditions.

Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that certain of the flow cytometric data shown in Fig. 6E on p. 1109 were strikingly similar to data that had appeared previously in a paper in the journal Toxicology and Applied Pharmacology written by different authors at different research institutes. In addition, a subsequent assessment of the data in the Editorial Office revealed that the cleaved caspase‑3 western blot data in Fig. 4A appeared to match with the protein bands featured in a larger gel slice shown to represent the Livin data in Fig. 5A. In view of the fact that the abovementioned data had already apparently been published prior to its submission to International Journal of Molecular Medicine, the Editor 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: 1103‑1111, 2020; DOI:10.3892/ijmm.2020.4481].