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The development of physiologically relevant three-dimensional (3D) culture systems is essential for modeling tumor complexity and improving the translational impact of cancer research. We established a 3D in vitro model of human hepatocellular carcinoma (HCC) using a marine collagen peptide-based (MCP-B) biomimetic hydrogel scaffold optimized for multicellular spheroid growth. Compared with conventional two-dimensional (2D) cultures, the MCP-B hydrogel more accurately recapitulated native tumor biology while offering simplicity, reproducibility, bioactivity, and cost efficiency. HCC cells cultured in MCP-B hydrogel displayed tumor-associated behaviors, including enhanced proliferation, colony formation, migration, invasion, and chemoresistance, and enriched cancer stem cell (CSC) populations. Molecular analyses revealed upregulated expression of genes associated with multidrug resistance; stemness regulation and markers; epithelial–mesenchymal transition (EMT) transcription factors, markers, and effectors; growth factors and their receptors; and cancer progression. The spheroids also retained liver-specific functions, suppressed apoptotic signaling, and exhibited extracellular matrix remodeling signatures. Collectively, these findings demonstrate that the 3D HCC model using MCP-B hydrogel recapitulates key hallmarks of tumor biology and provides a robust, physiologically relevant platform for mechanistic studies of HCC and CSC biology. This model further holds translational value for preclinical drug screening and the development of novel anti-HCC and anti-CSC therapeutics.

Polydopamine (PDA) surface coatings are widely used in biomedical engineering to enhance cell–substrate interactions; however, their effects on cancer-cell behavior remain unclear. In this study, we investigated how PDA-coated two-dimensional (2D) culture surfaces influence oncogenic traits of human prostate cancer (PC) cells in vitro. Using LNCaP, DU145, and PC3 cell lines, we found that PDA-coated substrates markedly increased the adhesion, migration, invasion, proliferation, and colony formation in a dose- and time-dependent manner. PDA exposure also induced epithelial–mesenchymal transition (EMT), upregulated cancer stem cell markers (CD44, CD117, CD133, Sox2, Oct4, and Nanog), and elevated expression of metastasis- and chemoresistance-associated molecules (MMP-2, MMP-9, MDR1, and MRP1). Mechanistically, PDA coatings enhanced integrin α2β1-associated cell adhesion, accompanied by increased focal adhesion kinase (FAK) phosphorylation and downstream activation of JNK signaling. Pharmacological inhibition of integrin α2β1 (BTT-3033), FAK (PF573228) and JNK (SP600125) effectively abrogated PDA-induced malignant phenotypes and restored chemosensitivity to cabazitaxel, cisplatin, docetaxel, curcumin, and enzalutamide. Collectively, these findings identify PDA-coated surfaces as a simple, efficient, and reductionist in vitro platform for studying adhesion-mediated signaling and phenotypic plasticity in PC cells, while acknowledging that further validation in three-dimensional (3D) and patient-derived models will be required to establish in vivo relevance.

Natural killer (NK) cells, key effectors of innate immunity, are classically categorized into CD56dim and CD56bright subsets in humans. While murine NK cell heterogeneity has become increasingly recognized, the classification of mature NK cell subsets remains incompletely defined. Here, we comprehensively characterized CD127+ NK cells in mice and identified them as a distinct, mature subset, developing independently of the thymus and interleukin (IL)-15 signaling. Flow cytometric analyses revealed that CD127+ NK cells are broadly distributed across lymphoid and non-lymphoid tissues—including in C57BL/6 wild-type and athymic Foxn1−/− mice—and exhibit a surface phenotype distinct from CD127− NK and thymus-derived CD127+ NK cells. Functional assays demonstrated that CD127+ NK cells produce interferon-γ and exert cytotoxic activity, despite expressing markers typically associated with immature NK cells. CD127+ NK cells were absent in IL-7Rα−/− mice but present in IL-15−/− and IL-15Rα−/− mice, indicating a selective dependence on IL-7 signaling. IL-7 promoted their proliferation and activation both in vitro and in vivo. These findings revise current models of NK cell development by identifying a novel, IL-7-responsive, IL-15-independent, thymus-independent, and functionally competent CD127+ NK cell subset that is phenotypically distinct from helper-like innate lymphoid cells (ILCs). This study provides a framework for future investigations on NK cell heterogeneity, tissue specialization, and cytokine-mediated regulation.

Polydopamine (PDA) surface coatings are widely used in biomedical engineering to enhance cell–substrate interactions; however, their effects on cancer-cell behavior remain unclear. In this study, we investigated how PDA-coated two-dimensional (2D) culture surfaces influence oncogenic traits of human prostate cancer (PC) cells in vitro. Using LNCaP, DU145, and PC3 cell lines, we found that PDA-coated substrates markedly increased the adhesion, migration, invasion, proliferation, and colony formation in a dose- and time-dependent manner. PDA exposure also induced epithelial–mesenchymal transition (EMT), upregulated cancer stem cell markers (CD44, CD117, CD133, Sox2, Oct4, and Nanog), and elevated expression of metastasis- and chemoresistance-associated molecules (MMP-2, MMP-9, MDR1, and MRP1). Mechanistically, PDA coatings enhanced integrin α[sub.2]β[sub.1]-associated cell adhesion, accompanied by increased focal adhesion kinase (FAK) phosphorylation and downstream activation of JNK signaling. Pharmacological inhibition of integrin α[sub.2]β[sub.1] (BTT-3033), FAK (PF573228) and JNK (SP600125) effectively abrogated PDA-induced malignant phenotypes and restored chemosensitivity to cabazitaxel, cisplatin, docetaxel, curcumin, and enzalutamide. Collectively, these findings identify PDA-coated surfaces as a simple, efficient, and reductionist in vitro platform for studying adhesion-mediated signaling and phenotypic plasticity in PC cells, while acknowledging that further validation in three-dimensional (3D) and patient-derived models will be required to establish in vivo relevance.

Polydopamine (PDA) surface coatings are widely used in biomedical engineering to enhance cell-substrate interactions; however, their effects on cancer-cell behavior remain unclear. In this study, we investigated how PDA-coated two-dimensional (2D) culture surfaces influence oncogenic traits of human prostate cancer (PC) cells in vitro. Using LNCaP, DU145, and PC3 cell lines, we found that PDA-coated substrates markedly increased the adhesion, migration, invasion, proliferation, and colony formation in a dose- and time-dependent manner. PDA exposure also induced epithelial-mesenchymal transition (EMT), upregulated cancer stem cell markers ( , , , , , and ), and elevated expression of metastasis- and chemoresistance-associated molecules ( , , , and ). Mechanistically, PDA coatings enhanced integrin α β -associated cell adhesion, accompanied by increased focal adhesion kinase (FAK) phosphorylation and downstream activation of JNK signaling. Pharmacological inhibition of integrin α β (BTT-3033), FAK (PF573228) and JNK (SP600125) effectively abrogated PDA-induced malignant phenotypes and restored chemosensitivity to cabazitaxel, cisplatin, docetaxel, curcumin, and enzalutamide. Collectively, these findings identify PDA-coated surfaces as a simple, efficient, and reductionist in vitro platform for studying adhesion-mediated signaling and phenotypic plasticity in PC cells, while acknowledging that further validation in three-dimensional (3D) and patient-derived models will be required to establish in vivo relevance.

To assess the effects of early goal-directed therapy (EGDT) on reducing mortality compared with conventional management of severe sepsis or septic shock. We included a systemic review, using the Medline and EMBASE. Seventeen randomized trials with 5765 patients comparing EGDT with usual care were included. There were no significant differences in mortality between EGDT and control groups (relative risk [RR], 0.89; 95% confidence interval [CI], 0.79-1.00), with moderate heterogeneity (I2=56%). The EGDT was associated with lower mortality rates when the mortality rate of the usual care group was greater than 30% (12 trials; RR, 0.83; 95% CI, 0.72-0.96), but not when the mortality rate in the usual care group was less than 30% (5 trials; RR, 1.03; 95% CI, 0.92-1.16). The mortality benefit was seen only in subgroup of population analyzed between publication of the 2004 and 2012 Surviving Sepsis Campaign guidelines, but not before and after these publications. This meta-analysis was heavily influenced by the recent addition of the trio of trials published after 2014. The results of the recent trio of trials may be biased due to methodological issues. This includes lack of blinding by incorporating similar diagnostic and therapeutic interventions as the original EGDT trial.

Hyaluronic acid (HA) is a linear high-molecular-weight polysaccharide with useful biomedical applications. Streptococcus zooepidemicus, a typical HA-producing bacterium, requires an animalderived nitrogen source such as tryptone, peptone or sheep blood as a nutrient. Sixteen nonanimal-derived (NAD) nitrogen sources were tested as a replacement for the expensive animalderived nitrogen sources, which may have safety issues. Among the sixteen tested NAD nitrogen sources, a yeast-derived nitrogen source (YE 0251) showed the highest HA productivity, which was equivalent to the control HA production medium containing tryptone in a 5-L jar and in 3,000-L industrial fermentations. In the 3,000-L fermentation, YE 0251 increased cell mass (dry cell weight) and HA production by 11% and 8%, respectively, compared with the control HA production medium. The final specific volumetric productivity (0.41 g/L • h) was improved by about 70% after reducing the fermentation time from 20 h to 12 h, compared to the conventional production medium.