Human Cell最新文献

Human cultured cells have been established from various normal and diseased tissues, serving as valuable in vitro cellular models. Normal cell strains play an important role in reference standards for human cells in in vitro experiments; however, they often lack essential features. In this study, 13 human cell strains derived from apparently normal three different tissues were examined to characterize their molecular signatures. Each cell strain exhibited sequence variants without any notable pathogenic mutations. Although cell strains originated from three types of tissues-lung, skin, and umbilical cord-were identified by the expression of EYA4, IGFBP3, and CXCL6, respectively, conventional cellular subtypes corresponding to in vivo tissue origins would not be applicable to the cell strains. Transcriptome analysis revealed that some key mesenchymal stromal cell (MSC) markers-NT5E, THY1, and ENG-were expressed in all 13 cell strains, implying that these cells represent immature fibroblasts possessing characteristics of MSCs. Mitochondrial DNA (mtDNA) copy number in the NB1RGB cell strain increased proportionally with the population doubling level (PDL), whereas HUC-F2 cells, which did not undergo freeze-thaw cycles, showed no change in mtDNA copy number at higher PDLs. This suggests that the influence of cryopreservation needs to be taken into account and that cultured cells can be assessed based on mtDNA copy number. Normal cell strains share common characteristics despite variations arising from human genetic diversity and tissue of origin, providing fundamental insights into cultured cells.

The pathogenesis of recurrent miscarriage (RSA) is highly complex. Studies indicate that abnormal polarization of decidual macrophages is critical for pregnancy failure. The aim of this research is to investigate the function of M1 polarization of macrophages in antiphospholipid syndrome (APS)-associated RSA and the potential mechanisms involved. Macrophages from decidual tissues was assessed by flow cytometry. In vitro, THP-1 monocytes were induced by anti-β2GPI/β2GPI and M1 polarization ratio was quantified. Pro-inflammatory cytokine levels were measured by ELISA, and TLR2/MyD88/NF-κB pathway proteins were analyzed via Western blot. To examine the impact of M1 macrophages on epithelial-mesenchymal transition (EMT), migration, and invasion of trophoblasts, THP-1 and HTR-8/SVneo cells were co-cultured. The NF-κB inhibitor JSH-23 was then applied to treat THP-1 cells to assess its impact on M1 macrophage-induced trophoblast behavior. An aPL-induced abortion mice model was constructed to determine whether blocking NF-κB could inhibit decidual macrophage M1 polarization and improve pregnancy outcomes. In RSA-aPL patients, decidual M1 macrophages proportion and TLR2 expression were significantly increased, and the MyD88/NF-κB pathway was activated. Anti-β2GPI/β2GPI triggered the differentiation of THP-1 cells into M1 macrophages and activated the TLR2/MyD88/NF-κB pathway, while silencing TLR2 suppressed the M1 polarization. Furthermore, M1-polarized macrophages inhibited EMT, migration, and invasion of HTR-8/SVneo cells, which could be reversed by JSH-23. Moreover, JSH-23 reduced M1 polarization of decidual macrophages in aPL-induced abortion mice, improving pregnancy outcomes. In conclusion, this study confirms that activation of the TLR2/MyD88/NF-κB pathway promotes the M1 macrophage polarization and has a significant impact on APS-associated RSA.

Coronary artery disease, a leading cause of mortality, underscores the need for biomarkers that can predict acute coronary syndrome (ACS) occurrence and outcomes. MicroRNAs (miRNAs) are increasingly recognized as potential markers. This study aimed to identify a plasma miRNA signature in ACS patients undergoing elective cardiac catheterization and to investigate miR-100's potential as an ACS prognostic biomarker. Plasma samples from 100 patients with suspected ACS were analyzed. qPCR revealed significantly elevated plasma miR-29a-3p, miR-100, miR-192, and miR-194-5p in ACS patients, and multiplex ELISA showed increased myeloperoxidase. Sub-network enrichment analysis identified TP53 as a central regulator of the miRNA-gene interaction network. In H9c2 cardiomyoblasts, hypoxic treatment (1% O₂) induced significant cytotoxicity and increased intracellular and released miR-100 levels. Western blotting further showed that hypoxia suppressed p53, HMGB1, NF-κB, and Bcl-2 expression. Consistent with the predicted regulatory network, siRNA-mediated p53 silencing markedly reduced constitutive miR-100 expression and triggered compensatory upregulation of inflammatory and survival-related proteins, including TLR4, NF-κB, and Bcl-2. Conversely, miR-100 overexpression significantly increased p53 protein levels and reduced the pro-survival factor Mcl-1, whereas miR-100 inhibition produced the opposite effect. These findings define a reciprocal p53/miR-100 regulatory axis that influences inflammatory and survival signaling in cardiomyoblasts. In conclusion, both clinical profiling and mechanistic studies support miR-100 as a promising early prognostic biomarker for ACS and suggest that hypoxia-induced disruption of the p53/miR-100 axis may contribute to cardiomyoblast vulnerability. Further studies are warranted to explore its therapeutic potential.

Gout, a common disease, develops after prolonged hyperuricemia with elevated serum uric acid (SUA) levels. Sex, overweight/obesity, heavy drinking, and aging all increase risk. Common dysfunctional variants (polymorphisms) in the ABCG2/BCRP gene are major genetic causes of gout/hyperuricemia. Early management would thus have potential benefits for public health. Several studies report the effectiveness of nurse-led care for gout management. We evaluate here the individual and population genetic effects of ABCG2 in 9244 Japanese study participants, in all of whom ABCG2 variants had a higher population-attributable fraction (PAF; approximately 30%) for progression of hyperuricemia than those for other typical environmental risk factors (overweight/obesity, heavy drinking, and aging). PAFs for aging in males and heavy drinking in females were not significant. All these factors also showed significant individual risk of increased SUA level, and ABCG2 variants had sufficient effect size to allow them to be converted into other environmental factors. To implement genome-personalized nursing, we then mapped onto the process a theoretical framework that is based on a psychological model from behavioral change theory. Because the present results for convertibility will improve the predictability of genetic effects, cognitive interventions by nurses based on individual variants could therefore encourage both inducements of behavioral change: efficacy expectations (self-efficacy) and outcome expectations. We conclude that the framework would function effectively based on cognitive interventions by nurses/paramedics. This theoretical framework has potential as a basis for implementing genome-personalized prevention, medicine and nursing of gout/hyperuricemia, and for optimizing nurse-led care.

HSPA8, a crucial molecular chaperone, has been implicated in the promotion of cancer across various malignancies. The clinical significance of HSPA8 in gastric cancer (GC) and its molecular contribution to tumour progression are unknown. Sequencing data from the GEO and TCGA databases, along with independent immunohistochemical data, revealed that HAPA8 was upregulated in GC tissues and was associated with tumour stage. HSPA8 knockdown decreased GC cell proliferation, migration, and invasion in vitro. According to the results of transcriptome sequencing and western blotting, HSPA8 suppression primarily affects the Wnt/β-catenin signalling and glycolysis pathways. In nude mice, HSPA8 knockdown drastically reduced tumour growth. The results of the current study validated the oncogenic function of HSPA8 in GC. Its overexpression is linked to GC development and poor clinicopathology.

Neuroinflammation is a key mechanism in epileptogenesis. Thiolutin (THL), an inhibitor of NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome, targets a central driver of the neuroinflammatory cascade. However, its role in regulating epileptogenesis and associated pathological changes remains unclear. In this study, we examined the effect of THL on epileptic seizures and neuropathological alterations. Electrode-implanted mice were stimulated with kainic acid (KA) to induce epileptic seizures and subsequently treated with THL, with MCC950 serving as a positive control. The anti-epileptic effects of THL were evaluated by recording brain wave changes and seizure scores, seizure frequency, and total duration within 2 h after KA induction. Cognitive function and neuropathological changes were assessed by the Morris water maze test, novel object recognition test, hematoxylin and eosin staining, Nissl staining, and TUNEL staining. NLRP3 inflammasome activation was analyzed by immunofluorescence and western blot. THL treatment improved brain waves, reduced seizure scores and frequencies, and shortened total seizure duration in KA-induced epileptic mice. THL treatment also reduced neuronal loss, attenuated neuronal apoptosis, and improved cognitive dysfunction in epileptic mice, accompanied by reduced activation of NLRP3 inflammasomes in hippocampal neurons and microglia. These findings suggest that THL exerts neuroprotective effects by blocking NLRP3 inflammasome activation, thereby mitigating neuroinflammatory responses, neuronal injury, and cognitive dysfunction in epileptic mice. Collectively, our results highlight THL as a promising therapeutic agent for epilepsy.

Esophageal cancer (EC) remains a highly aggressive malignancy with limited therapeutic success, partly due to heterogeneous responses to neoadjuvant chemotherapy (NAC). Tumor-derived exosomes and tumor-associated macrophages play critical roles in shaping the immunosuppressive tumor microenvironment, but their crosstalk in EC chemoresistance remains unclear. In this study, we identified tumor-derived exosomal miR-145-5p as a potential predictor of poor NAC response. Elevated exosomal miR-145-5p levels were associated with increased M2 macrophage infiltration and enhanced expression of M2 markers in EC tissues. Mechanistically, miR-145-5p promoted M2 macrophage polarization through the suppression of transferrin receptor (TFRC) and subsequent disruption of iron uptake. Consequently, these tumor-promoting M2-polarized macrophages enhanced EC cell proliferation, migration, invasion, and cisplatin resistance. In vivo, macrophages overexpressing miR-145-5p facilitated tumor growth and markedly weakened the therapeutic effects of cisplatin. Overall, our findings reveal that EC cells utilize exosomal miR-145-5p to remodel macrophages into a pro-tumorigenic phenotype through TFRC-dependent iron metabolic reprogramming, contributing to malignant progression and chemoresistance. Exosomal miR-145-5p may represent a promising biomarker for NAC response and a therapeutic target to improve treatment outcomes in EC.

Human cellular models used as materials in 183 articles published in *Human Cell* during 2025 comprise a total of 313 samples (Table 1, Tables S1, S2). This highlights current trends in research involving human cells and raises concerns about the use of these materials.

The interaction between the transforming growth factor beta (TGFβ) signaling pathway and long non-coding RNAs (lncRNAs) has been known to contribute to the progression and metastasis of digestive system cancers. Dysregulated expression of lncRNAs associated with the TGFβ-Smad signaling pathway is correlated with several clinical features in digestive system cancers. These lncRNAs regulate multiple biological functions, including epithelial-to-mesenchymal transition (EMT), tumor growth, and immune responses. They interact with key molecules in the TGFβ-Smad pathway to influence gene transcription and cellular behavior. Alterations in the expression of these lncRNAs can serve as valuable biomarkers for early detection and prognosis. Targeting the lncRNA-TGFβ axis offers a novel approach to cancer treatment. This review summarizes the interactions between the TGFβ signaling pathway and lncRNAs in digestive system cancers, highlighting their potential in diagnosis, prognosis, and therapy.