Current Molecular Medicine - Online First

Gastrointestinal cancers, including esophageal cancer, gastric cancer, liver cancer, pancreatic cancer, and colorectal cancer, are a major health burden worldwide, characterized by high incidence and mortality rates. Traditional diagnostic methods are not satisfactory. The compliance of patients with endoscopic examinations is poor, and the sensitivity and specificity of conventional tumor markers are also not high. Liquid biopsy, especially the detection of exosomal microRNAs (miRNAs), as a promising alternative method, has emerged, among which the miR-200 family has been identified as a key regulatory factor in the pathogenesis of gastrointestinal cancers.

A literature search was conducted from 2002 to 2025, and the keywords used included “gastrointestinal cancer”, “miR-200 family”, and “exosomal miRNA”. The studies involved included those on the role of miR-200 in gastrointestinal cancers, as well as research on exosomal miR-200 as a biomarker or therapeutic target. Inclusion criteria include: original studies published in English and peer-reviewed, which explored the biological, diagnostic, prognostic, or therapeutic effects of the miR-200 family in gastrointestinal cancers, and provided the complete papers that are accessible. If the research is a review, a conference summary, an editorial, a duplicate dataset, or lacks sufficient experimental or clinical data related to miR-200, it will be excluded. This literature search was conducted in the PubMed database. After screening, a total of 248 articles were obtained, and finally, 133 studies were included in the analysis. This review adhered to the guidelines of SANRA and employed a narrative research method. The key findings were qualitatively synthesized to summarize the mechanism of miR-200 and its clinical relevance.

MicroRNA-200 regulates the occurrence and development of gastrointestinal cancers by modulating epithelial-mesenchymal transition (EMT), angiogenesis, cancer stem cell properties, and chemotherapy resistance. Its expression in tumor tissues is closely related to clinical pathological features, prognosis, and treatment response. Furthermore, the miR-200 present in exosomes exhibits extremely high stability in circulation and specificity towards cancer.

Studies have shown that miR-200 family regulates the occurrence and development of gastrointestinal cancer by targeting epithelial-mesenchymal transition, angiogenesis, and other characteristics, and its expression is related to clinicopathological characteristics and prognosis. Exosomal miR-200 family has shown good diagnostic performance in gastrointestinal malignancies. In an independent validation cohort, the AUC of combined miR-200a-3p and miR-200b-3p expression in pancreatic ductal adenocarcinoma (PDAC) was 0.97, with a sensitivity of 100% and a specificity of 88%. Notably, combining this miRNA combination with CA19-9 further improved diagnostic accuracy, increasing the AUC of the combined model from 0.86 for CA19-9 alone to 0.997. In addition, miR-200c had a moderate but significant diagnostic and prognostic value for GC, with a combined AUC of 0.75, a sensitivity of 0.74, and a specificity of 0.66. Limitations such as the heterogeneity of studies and the unclear mechanism of exosome packaging can be alleviated by standardized protocols. Future studies should focus on large-scale multi-center trials, in-depth exploration of molecular mechanisms, and standardization of experimental workflow.

Exosomal miR-200 overcomes the limitations of traditional diagnosis and is expected to become a biomarker and therapeutic target for gastrointestinal tumors. The miR-200 family had the strongest diagnostic evidence in pancreatic ductal adenocarcinoma (AUC = 0.97, sensitivity = 100%, specificity = 88%) and gastric cancer (AUC = 0.75, sensitivity = 74%, specificity = 66%). These data highlight its translational potential as a clinically relevant biomarker for early and non-invasive gastrointestinal cancer detection. Validation in large cohorts and the development of targeted therapies will be essential to improve patient outcomes.

The p53 protein plays a major role in maintaining genome stability as well as the response of cells to stress. One of the principal things that regulates p53 is MDM2, and the way it interacts with p53 is of great significance in the degradation of p53. This dephosphorylation of p53 by Wip1 increases its affinity to MDM2, which causes p53 degradation. Wip1 is used to increase the growth of tumors by undermining the p53 pathway. However, the active form of p53 can be retained with the help of preventing Wip1, and this fact makes it useful as a target of cancer treatment. An ever-increasing body of preclinical evidence suggests the possibility that Wip1 inhibitors would be used alongside potent MDM2 inhibitors to enhance p53 activity and enhance treatment outcomes. The purpose of the review was to examine studies pertaining to the action of a Wip1 inhibitor and Nutlin-3a in order to induce p53 functionality.

We searched Google Scholar, PubMed, and other search engines using such terms as MDM2 inhibitors, Wip1 inhibitors, and Nutlin. Newer articles published after 2020 were chosen to ensure that the recent findings are included.

Wip1, an attractive antineoplastic target to control the p53 pathway, is a dephosphorylator of p53 at serine-15. Nutlin-3a with a Wip1 inhibitor appears to act synergistically to push p53 half-maximal inhibitory concentrations (IC50) into the low micromolar range. This combination greatly stimulates downstream p53-dependent response, which leads to a strong reduction of cell proliferation.

We find that MDM2 inhibitors in combination with Wip1 inhibitors are synergistic in stimulating p53 activity. The results emphasize the need to use a combination of p53 induction and the inactivation of its suppressors in the treatment of cancer.

As p53 is the most commonly mutated gene across a broad range of tumors, enhancing p53 activity is a prerequisite for achieving potent therapeutic effects. We envision that combination therapies involving Nutlin-3a, Wip1 inhibitors, and other effective cancer treatments may synergistically improve p53 activity and enhance therapeutic outcomes.

This study aimed to investigate the regulatory mechanism of the LncRNA HULC/miR-556-5p axis in endothelial cell injury associated with heart failure and its impact on endothelial cell function. Specifically, we explored how HULC interacts with miR-556-5p to modulate cell survival, apoptosis, inflammation, and autophagy in response to Ang II-induced injury.

Human cardiac microvascular endothelial cells (HCMECs) were utilized as the study model. Ang II-induced HCMEC injury was simulated by treating cells with 100 nM Ang II for 24 hours. The expression levels of HULC, miR-556-5p, and related proteins were assessed using techniques, such as real-time quantitative PCR and Western blot. Cell apoptosis was detected using flow cytometry, and inflammatory cytokine release (TNF-α, IL-1β, and IL-6) was analyzed via ELISA. Cell viability was assessed using MTT assays. Immunoblotting was employed to evaluate the phosphorylation status of key signaling molecules, including AMPK and FOXO3.

We observed a crucial role of the LncRNA HULC/miR-556-5p axis in Ang II-induced HCMEC injury. Overexpression of HULC significantly suppressed miR-556-5p activity, thereby reducing cell apoptosis and the release of inflammatory cytokines while promoting cell survival. Further experimental results indicated that miR-556-5p regulated cell function by reducing the expression level of FOXO3 and modulating the AMPK signaling pathway. Additionally, miR-556-5p markedly decreased cellular autophagy levels, further supporting its regulatory role in endothelial cell injury associated with heart failure.

This study elucidates the important role of the LncRNA HULC/miR-556-5p axis in endothelial cell injury associated with heart failure. Our findings provide new insights into the pathophysiological mechanisms of heart failure and highlight the potential therapeutic value of targeting this axis to improve endothelial cell function.

Stem cells play a pivotal role in immunomodulation and tissue repair, and their functions can be influenced by TLR signaling. The Toll/interleukin-1 receptor domain-containing protein C (TcpC), secreted by Uropathogenic Escherichia coli, can inhibit host immunity by interfering with TLR pathways. As mitochondria are crucial for stem cell function, there may be links between TcpC and mitochondrial homeostasis.

We isolated MSC mitochondria using magnetic beads coated with a monoclonal antibody against the outer mitochondrial membrane protein OMP25 and conducted a proteomic study to examine the MSC mitochondrial proteome with or without TcpC. Bioinformatics analyses, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and protein-protein interaction (PPI) network analysis, were employed.

A total of 33 proteins with significant changes in abundance were identified: 4 increased in abundance, including glycolytic enzymes (Pkm [FC=1.6599, p=0.0217]) and stress response proteins (Ywhaq [FC=1.4666, p=0.04502]); and 29 decreased, mainly related to mitochondrial oxidative phosphorylation (e.g., Atp5f1e [FC=0.001, p=0.00120], Ndufa11 [FC=0.001, p=0.00674]) and protein quality control (e.g., Grpel1 [FC=0.46663, p=0.02083], Hspa9 [FC=0.48089, p=0.0435], Pitrm1 [FC=0.12764, p=0.01388]).

The possible effects of TcpC on the MSC mitochondrial proteome are reported here for the first time. This information provides a clearer understanding of MSCs in the context of infectious disease and offers a scientific basis for future stem cell therapy research.

TCP-C intervention leads to a series of differentially expressed proteins in MSC mitochondria, which are involved in several functional clusters, including oxidative phosphorylation, respiratory electron transport, the tricarboxylic acid cycle, glyoxylate and dicarboxylate metabolism, branched-chain amino acid catabolism, and cristae formation.

Menstrual hygiene practices are a critical health concern, and if neglected, they may lead to reproductive tract infections (RTIs), toxic shock syndrome, and other vaginal diseases. To prevent these conditions, antiseptic and antibacterial properties must be incorporated into sanitary napkins.

In this study, nanolayered topsheets were synthesized by embedding silver nanoparticles (AgNPs) into PVA in Aloe vera extract, which was then coated onto a non-woven fabric. The polymer-entrapped AgNPs in Aloe vera (AgNPs + PVA + Aloe vera) were characterized using UV-visible spectrometry, dynamic light scattering (DLS), zeta potential, FTIR, and SEM analyses.

The release kinetics of AgNPs from the coated fabric were studied in simulated vaginal fluid (SVF), showing an initial burst release followed by sustained release. The toxicity of the released nanosilver was evaluated both in vitro using A375 cells and in vivo using zebrafish embryos, establishing a safe dose of 3 μM. The antimicrobial effect of the coated fabric was tested against S. aureus and E. coli, showing clear zones of inhibition.

The AgNPs and the coated fabric demonstrated comparable antimicrobial activity.

This product has potential for use in coating sanitary napkins to provide skin-soothing and antimicrobial effects.

Sorafenib is a first-line drug for hepatocellular carcinoma (HCC). Understanding the regulatory mechanisms of sorafenib resistance is critical to inhibit sorafenib resistance and develop novel therapeutic strategies. Here, we aimed to study the role of SSR2 (signal sequence receptor subunit 2) in sorafenib resistance of HCC.

3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, colony formation assay, and cell viability assay were used to determine the role of SSR2 in sorafenib resistance of HCC. Co-immunoprecipitation (CoIP) was used to determine the interacting protein of SSR2.

We found SSR2 was upregulated in sorafenib-resistant HCC tissues. In addition, in HCC patients, SSR2 was associated with both poor response to sorafenib and poor clinical outcomes. Functional assay showed that SSR2 promoted sorafenib resistance in HCC cells. Mechanistically, SSR2 suppressed ferroptosis. Further analysis showed that SSR2 interacted with ferroptosis master regulator glutathione peroxidase 4 (GPX4) and increased the catalytic activity of GPX4, leading to inhibition of ferroptosis. Induction of ferroptosis could reverse the promotion effect of SSR2 overexpression on sorafenib resistance.

SRR2 plays a critical role in sorafenib resistance generation. However, the detailed mechanism of SRR2 increasing the catalytic activity of GPX4 will be further studied.

In summary, we reveal that SSR2 enhances sorafenib resistance of HCC via interacting with GPX4 and inhibiting ferroptosis, providing a potential target for HCC treatment. The molecular mechanism of GPX4-SSR2 interaction in ferroptosis will be further studied.

Intrauterine Adhesions (IUA), a common gynecological condition often caused by infection or endometrial injury, significantly impact women's reproductive and mental health. Its unclear pathogenesis hinders the development of effective treatments. Adiponectin, a bioactive protein with anti-inflammatory and anti-fibrotic properties, may offer therapeutic potential. This study investigates adiponectin's effects and mechanisms in IUA to inform new clinical strategies..

Endometrial tissues from IUA patients and controls were analyzed via immunohistochemistry to assess NLRP3, IL-1β, TGF-β1, and adiponectin expression. A human IUA cell model was established by stimulating human endometrial stromal cells (HESCs) with TGF-β1 (10 ng/ml, 48 hours). Interventions using the NLRP3 inhibitor MCC950, activator nigericin sodium salt, and adiponectin were applied. Protein and mRNA expression levels of NLRP3, IL-1β, TGF-β1, α-SMA, and COL1A1 were evaluated via Western blot and RT-qPCR. In vivo, IUA model rats were treated with adiponectin, and uterine morphology, gland count, collagen deposition, and inflammatory/fibrotic markers were analyzed.

NLRP3, IL-1β, and TGF-β1 expression were significantly upregulated in IUA patient tissues, while adiponectin was downregulated (P<0.05). In the TGF-β1-induced IUA cell model, NLRP3 inhibition with MCC950 reduced IL-1β and TGF-β1 levels, whereas NLRP3 activation with nigericin increased them. Adiponectin intervention significantly decreased NLRP3, IL-1β, TGF-β1, α-SMA, and COL1A1 expression in vitro (P<0.05). In IUA rats, adiponectin improved uterine morphology, increased endometrial glands, reduced collagen fiber deposition, and downregulated NLRP3, IL-1β, and TGF-β1 expression (P<0.05).

Adiponectin alleviates endometrial inflammation and fibrosis in IUA, potentially by modulating the NLRP3/IL-1β/TGF-β1 signaling pathway. These findings highlight adiponectin’s role in mitigating IUA progression and provide a theoretical basis for its clinical applications.

Adiponectin reduces inflammation and fibrosis in IUA by suppressing the NLRP3/IL-1β/TGF-β1 axis, offering new insights for IUA treatment strategies.

The present study aimed to examine the functions of heat shock protein 90 (HSP90), NF-κB, C3, and C5a in cardioprotective effects induced by vericiguat in mice.

Male mice were randomly assigned to six groups: sham, ischemia/ reperfusion (I/R), vericiguat preconditioning (VPre), VPre + HSP90 inhibitor geldanamycin (GA), vericiguat postconditioning (VPost), and VPost + GA. An experimental mouse model of I/R was established in mice through surgery and treatments with vericiguat and GA. The following parameters were assessed: myocardial infarct size; cardiomyocyte apoptosis; cTnI, CK-MB, and LDH serum levels, protein expression levels of Bcl-2, Bax, HSP90, NF-κB, and complement components C3 and C5a, and mRNA expression levels of IL-1β, TNF-α, and ICAM-1.

Vericiguat significantly attenuated the myocardial infarct size induced by I/R injury; suppressed cardiomyocyte apoptosis; reduced serum levels of myocardial markers (CK-MB, LDH, and cTnI); decreased C5a, and C3 levels, NF-κB signaling, and expression of inflammatory cytokine (ICAM-1,TNF-α, and IL-1β); and enhanced HSP90 and Bcl-2 expression levels. However, GA reversed these effects.

The study contributes to the investigation of the crosstalk between HSP90 and complement in the protective effects of vericiguat on myocardial I/R injury. However, further in-depth research is needed to explore the underlying mechanisms of vericiguat's cardioprotective effects against myocardial I/R injury.

HSP90 plays a crucial role in the cardioprotective effects of vericiguat, providing new insights into its mechanisms of action.