Human Cell[JOURNAL]
Sun
200 papers
An overview of the developments in 3D cancer cell models, assay techniques, and imaging modalities.
Wheeler NH, Dada KA, Minnaar CA
Hum Cell · 2026 Apr · PMID 41934569 · Full text
Cancer biology is a constantly evolving field of study due to the dynamic and complex nature of biological systems. The unique role of in vitro assays in cell biology has led to numerous transformations in our understand...
Cancer biology is a constantly evolving field of study due to the dynamic and complex nature of biological systems. The unique role of in vitro assays in cell biology has led to numerous transformations in our understanding of the functional and structural details of the cells and tissues that comprise these systems. However, the traditional monolayer assays have been reported to fall short of the in vivo physiology of cells. This has led to the development of 3D cell models, such as spheroids and organoids, that aim to recapitulate the intricate structural and functional behaviour of in vivo tumours. This review describes passive methods of spheroid formation (scaffold-free and scaffold-based) and the limitations that have driven the development of engineered active design methods to increase the physiological relevance of the model. Traditional assays need to be modified to evaluate these models, accounting for their architecture, density, and microenvironment gradients. Current developments in performing 3D cell assays include increased reagent concentration and incubation periods; however, many protocols still require single-cell analysis. We present a review of assay developments that maintain the spatial and contextual information that makes the 3D models physiologically relevant. Additionally, we introduce the advances in microscopy techniques that provide deeper visualisation of these models.
Ubiquitously expressed prefoldin-like chaperone (UXT) regulates putrescine metabolism and promotes colorectal cancer progression.
Chen M, Huang S, Gong L … +3 more , Wu X, Li Y, Wu H
Hum Cell · 2026 Apr · PMID 41931169 · Publisher ↗
Colorectal cancer (CRC) is a prevalent and increasingly common malignancy that poses significant threats to patient survival and quality of life. This study investigates the role of ubiquitously expressed prefoldin-like...
Colorectal cancer (CRC) is a prevalent and increasingly common malignancy that poses significant threats to patient survival and quality of life. This study investigates the role of ubiquitously expressed prefoldin-like chaperone (UXT) in regulating polyamine metabolism, particularly putrescine, and its impact on CRC progression. Through comprehensive bioinformatics analysis, UXT was identified as a key factor positively correlated with putrescine abundance in CRC cell lines. Clinical samples confirmed upregulation of UXT and its positive correlation with putrescine levels. Functional assays revealed that UXT knockdown reduced cell viability, migration, and invasion, while overexpression enhanced these phenotypes. Additionally, UXT knockdown decreased putrescine levels and increased the expression of ornithine decarboxylase antizymes (OAZ1, OAZ2, OAZ3), which negatively regulate polyamine synthesis. Conversely, UXT overexpression exhibited the opposite effects. In vivo experiments using a subcutaneous xenograft tumor model in nude mice showed that UXT overexpression enhanced tumor growth and putrescine levels, and UXT overexpression is associated with an increase in M2 macrophage markers, along with reduced M1-associated markers, while UXT knockdown inhibited these effects. These findings suggest that UXT contributes to CRC progression by regulating polyamine metabolism and macrophage polarization, demonstrating its potential as a therapeutic target to disrupt metabolic pathways essential for cancer cell survival and proliferation.
Advancing diagnostic biomarkers in Alzheimer's disease: interdisciplinary innovations and technological frontiers.
Patwekar F, Patwekar M, Wei LS … +3 more , Sharma R, Varghese R, Mohammed A
Hum Cell · 2026 Apr · PMID 41925947 · Publisher ↗
Developing diagnostic biomarkers for Alzheimer's disease (AD) is at the cutting edge of interdisciplinary research and technical advancement. This comprehensive analysis investigates potential options for improving diagn...
Developing diagnostic biomarkers for Alzheimer's disease (AD) is at the cutting edge of interdisciplinary research and technical advancement. This comprehensive analysis investigates potential options for improving diagnostic accuracy and early detection of AD. Identifying biomarkers other than Aβ and tau proteins, such as synaptic dysfunction markers and metabolic indicators, is a novel technique. Integrating multi-omics data provides a comprehensive picture of AD pathophysiology, assisting in the discovery of biomarkers and treatment targets. Advances in technology, notably nanotechnology and biosensors, show promise for highly sensitive and specific platforms capable of identifying AD-related biomarkers in physiological fluids. AI and machine learning algorithms are critical in analyzing large datasets, improving pattern identification, and increasing diagnostic accuracy. Predictive models based on various biomarkers and clinical data open the way for personalized medicine methods in the treatment of AD. More advancements in PET and MRI tracers are required for targeted and sensitive imaging of specific AD-related clinical alterations. Wearing gadgets and seeing digital health signs have helped us to find diseases early and track them over time. They even allow monitoring from afar and all the time. This comprehensive review brings together new developments and teamwork across different fields. In this way, it guides to enhance how to identify AD. By mixing these new methods, we aim to change the diagnosis of AD early and accurately. This allows us to focus on treatments and push forward new cures for AD.
CBC3T-3: a novel patient-derived cisplatin-resistant distal cholangiocarcinoma cell line harboring multiple TP53 missense mutations.
Xi J, Bai M, Zhong R … +14 more , Huang C, An R, Gao L, Ma H, Tian L, Zhao J, Jiang N, He X, Wang L, Dong Z, Yue P, Lin Y, Bai Z, Meng W
Hum Cell · 2026 Mar · PMID 41917613 · Full text
Distal cholangiocarcinoma (dCCA) is a malignant tumor characterized by a challenging diagnosis, high invasiveness, and extremely poor prognosis. Research on dCCA is limited by the scarcity of reliable patient-derived pre...
Distal cholangiocarcinoma (dCCA) is a malignant tumor characterized by a challenging diagnosis, high invasiveness, and extremely poor prognosis. Research on dCCA is limited by the scarcity of reliable patient-derived preclinical tumor models. This study established a novel human distal cholangiocarcinoma cell line, CBC3T-3, and systematically characterized its biological properties, genomic features, and potential for clinical application. This cell line was extracted from postoperative distal cholangiocarcinoma tumor from a 54-year-old male patient. It was stably passaged (> 50 generations) through primary culture and condition optimization, preserving the same pathology as that of the primary tumor. Whole-exome sequencing (WES) confirmed somatic mutations, tumor mutation burden, single-sample clonal structure, driver genes, and drug resistance genes in CBC3T-3 cells, revealing their genomic characteristics. Functional assays demonstrated that CBC3T-3 cells exhibit strong capabilities for proliferation, migration, and invasion in vitro. In a subcutaneous xenograft model in immunodeficient mice, palpable tumor nodules developed within 4 weeks, reflecting the clinical characteristics of rapidly progressive disease. Drug sensitivity analysis revealed that, compared with TFK-1 cells, CBC3T-3 cells presented significantly greater responses to paclitaxel, gemcitabine, and oxaliplatin but relatively poor responses to 5-FU and cisplatin. The integration of drug resistance gene findings from WES suggests that TP53 missense mutations may mediate primary resistance to cisplatin. The establishment of the CBC3T-3 cell line enhances the research toolkit for dCCA. Its genomic characteristics and functional plasticity provide a reliable preclinical tumor model for developing precision therapies and investigating drug resistance mechanisms.
Arginine deprivation induces ROS dependent autophagic cell death in human acute myeloid leukemia cells.
Taki F, Farhat M, El-Atat O … +3 more , Al-Samman S, Assaf N, Abi-Habib RJ
Hum Cell · 2026 Mar · PMID 41910852 · Publisher ↗
In this study, we assess the activation of autophagy and its impact on cytotoxicity following [HuArgI (Co)-PEG5000]-induced arginine deprivation in AML cells. We have previously shown that arginine deprivation is selecti...
In this study, we assess the activation of autophagy and its impact on cytotoxicity following [HuArgI (Co)-PEG5000]-induced arginine deprivation in AML cells. We have previously shown that arginine deprivation is selectively cytotoxic to AML cells and that cell death is caspase independent and non-apoptotic, hence the mechanism of cell death remained elusive. We tested a panel of 7 AML cell lines, and we first demonstrated that the cytotoxicity of [HuArgI (Co)-PEG5000] to AML cells is long-term and sustained despite re-expression of overexpression of ASS1 in all cell lines. We also demonstrated that arginine deprivation leads to a prolonged and extensive activation of autophagy starting at 24 and lasting up to 120 h in all cells. Autophagy was shown to induce cell death since its inhibition using chloroquine (CQ) significantly decreased [HuArgI (Co)-PEG5000]-induced cytotoxicity, indicating autophagic cell death in AML cells following arginine deprivation. Moreover, we showed that arginine deprivation leads to ROS accumulation and that neutralizing ROS using N-acetylcysteine (NAC) does not affect the autophagic response but completely reverses the cytotoxicity of arginine deprivation, demonstrating that death by autophagy is dependent on ROS generation in AML cells.
Rolled amniotic membrane for practical vascular graft development: a scoping review.
Murtadha AH, Anuar NNM, Ishak MF … +2 more , Yazid MD, Sulaiman N
Hum Cell · 2026 Mar · PMID 41843024 · Publisher ↗
Small-diameter vascular grafts remain a clinical challenge due to thrombosis, stenosis, and poor long-term patency of synthetic substitutes. Decellularised human amniotic membrane (dHAM), derived from placental tissue, o...
Small-diameter vascular grafts remain a clinical challenge due to thrombosis, stenosis, and poor long-term patency of synthetic substitutes. Decellularised human amniotic membrane (dHAM), derived from placental tissue, offers a promising alternative because of its natural extracellular matrix, low immunogenicity, and broad availability. A scoping review was conducted to assess the practicality of rolling dHAM as a tubular vascular graft. Systematic searches of PubMed, Scopus, Web of Science, and EBSCOhost identified 238 records. After duplicate removal and screening, eight studies met the inclusion criteria and were analysed. dHAM was fabricated into multilayered tubular constructs with customisable dimensions. Decellularisation protocols efficiently removed cellular components while preserving ECM integrity, resulting in strong in vitro biocompatibility and mechanical performance. The addition of silica nanoparticles improved graft robustness by enhancing interfacial self-adherence. Preclinical studies in rats and rabbits demonstrated successful implantation with long-term patency up to 16 months, with minimal thrombosis, stenosis, or aneurysm formation. In a porcine carotid model, dHAM outperformed expanded polytetrafluoroethylene by reducing neointimal hyperplasia and promoting endothelialisation. dHAM offers tunable mechanical performance, regenerative potential, and accessibility, positioning it as a strong candidate for small-diameter vascular grafts. To advance towards clinical application, the existing body of evidence remains limited, underscoring the need for further research to evaluate rolling-based strategies and their reproducibility, optimisation potential, and clinical translatability.
Unveiling TNFRSF19: a novel tumor suppressor targeting endoplasmic reticulum stress and LGR5/Wnt/β-catenin in cervical cancer.
Wei X, Su L, Chen R … +2 more , He T, Wu C
Hum Cell · 2026 Mar · PMID 41840262 · Publisher ↗
TNF Receptor Superfamily Member 19 (TNFRSF19) has been implicated in the advancement of several types of cancer. However, its function and mechanism in cervical cancer (CC) remain unclear. Additionally, while ER stress i...
TNF Receptor Superfamily Member 19 (TNFRSF19) has been implicated in the advancement of several types of cancer. However, its function and mechanism in cervical cancer (CC) remain unclear. Additionally, while ER stress is proposed as a therapeutic target in cancer, its relationship with TNFRSF19 in CC is unknown. This study aimed to investigate the role and underlying mechanisms of TNFRSF19 in CC. The expression of TNFRSF19 was investigated utilizing the GEPIA database and subsequently validated in 35 paired clinical CC tissue samples. The impact of TNFRSF19 overexpression on cellular proliferation, apoptosis, and endoplasmic reticulum (ER) stress was evaluated in C33A and HeLa cell lines through CCK-8 assays, colony formation assays, and flow cytometry. The interaction between TNFRSF19 and LGR5, along with its inhibitory effect on the Wnt/β-catenin pathway, was analyzed using co-immunoprecipitation (Co-IP), immunofluorescence, and western blotting techniques. Additionally, an in vivo xenograft tumor model in nude mice was developed to substantiate the tumor-suppressive function of TNFRSF19. TNFRSF19 expression was significantly reduced in CC tissues and cell lines. TNFRSF19 overexpression substantially inhibited cell proliferation and colony formation, and induced apoptosis in vitro, while also suppressing tumor growth in vivo. Mechanistically, TNFRSF19 facilitated apoptosis through the activation of ER stress and directly interacted with LGR5 to inhibit the LGR5/Wnt/β-catenin pathway. The pro-apoptotic and tumor growth-inhibitory effects induced by TNFRSF19 were diminished by the ER stress inhibitor 4-phenylbutyric acid (4-PBA). Moreover, the inhibitory effect on cell proliferation mediated by TNFRSF19 was effectively reversed upon the restoration of LGR5 expression. This study demonstrates that TNFRSF19 functions as a novel tumor suppressor in CC by activating ER stress and inhibiting the LGR5/Wnt/β-catenin pathway, highlighting its potential as a therapeutic target for CC treatment.
Femtosecond label-free imaging evaluates the metabolism of mesenchymal stromal cells.
Liu J, Liu Y, Xiong B … +4 more , Cao H, Li X, Tian C, Wang H
Hum Cell · 2026 Mar · PMID 41803368 · Publisher ↗
Mesenchymal stromal cells (MSCs) hold significant promise in regenerative medicine, yet their clinical application is hindered by challenges such as cellular heterogeneity and quality control. This study aims to develop...
Mesenchymal stromal cells (MSCs) hold significant promise in regenerative medicine, yet their clinical application is hindered by challenges such as cellular heterogeneity and quality control. This study aims to develop a rapid, noninvasive method for evaluating the quality of MSCs using femtosecond laser label-free imaging (FLI). We examined the proliferation, metabolic dynamics, and differentiation potential of MSCs from various tissue sources, including human dental pulp, umbilical cord, and fat, across different passages. Conventional experiments show that as the number of passages increases, the morphology of MSCs alters, proliferation capacity decreases, β-galactosidase activity linked to aging rises, and both osteogenic and adipogenic differentiation abilities markedly decline. FLI technology effectively captures these changes: reduced NAD(P)H/FAD ratio in higher-passage cells suggests decreased metabolic activity, while enhanced aging-related fluorescence signals, such as lipofuscin, align with cellular senescence. In the assessment of differentiation capability, increased fluorescence intensity of NAD(P)H and FAD signals indicates heightened metabolic activity within the cells. With the passages increasing, the fluorescence intensities of NAD(P)H and FAD decline, suggesting diminished ability of cell differentiation. Furthermore, during osteogenic differentiation, the optical REDOX ratio (FAD/(NAD(P)H + FAD)) decreases with successive passages, whereas during adipogenic differentiation, it increases. Three-dimensional FLI of suspension cells further reveals that the cells of lower-passage exhibit greater spatial heterogeneity in metabolic signals, possibly reflecting more active mitochondrial function. This study demonstrates that FLI technology can effectively assess the proliferation activity, senescence, and differentiation potential of MSCs through noninvasive, dynamic monitoring of their metabolic status and morphological features, offering a novel approach for standardized quality assessment of MSCs preparations.
Establishment and characterization of NCC-GCTB16-C1: novel patient-derived cell line of giant cell tumor of bone.
Kono K, Shiota Y, Osaki J … +9 more , Shu TT, Kamio S, Iwata S, Nishino S, Yoshida A, Ohtsuki S, Ohtori S, Kawai A, Kondo T
Hum Cell · 2026 Mar · PMID 41801630 · Publisher ↗
Giant cell tumor of bone (GCTB) is a locally aggressive osteolytic bone tumor characterized by recurrent mutation in the H3-3A gene. Although surgical resection remains the mainstay of treatment, a considerable proportio...
Giant cell tumor of bone (GCTB) is a locally aggressive osteolytic bone tumor characterized by recurrent mutation in the H3-3A gene. Although surgical resection remains the mainstay of treatment, a considerable proportion of patients experience local recurrence or pulmonary metastasis, and effective systemic therapy has not yet been established. Given the inherent clinicopathological heterogeneity of GCTB, we established a novel patient-derived cell line, NCC-GCTB16-C1, from the primary tumor of a patient with GCTB to expand the experimental resources available for translational research. The cells exhibited stable proliferation over a 3-month period, retained the characteristic H3-3A mutation, and formed spheroids with variable morphologies under three-dimensional conditions. They also demonstrated invasive and migratory behavior consistent with the biological properties of GCTB. Proteomic analysis revealed that NCC-GCTB16-C1 exhibited properties similar to those of the original tumor tissue. Thus, NCC-GCTB16-C1 provides an in vitro model that faithfully reflects the molecular and phenotypic features of GCTB, offering a valuable tool for mechanistic studies and preclinical drug evaluation.
Herbacetin alleviates acute doxorubicin cardiotoxicity via regulating the ERK1/2-FOXO3a signaling pathway.
Bian S, Li X, Zhu P … +6 more , Jiang Z, Yan C, Wei S, Luo L, Zhu Y, Luo L
Hum Cell · 2026 Mar · PMID 41774278 · Publisher ↗
Doxorubicin (DOX) is a commonly prescribed chemotherapeutic regimen, but its practice is challenged by cardiotoxicity risks. Herbacetin (HBT), a bioactive flavonoid compound, has demonstrated anti-oxidative, anti-inflamm...
Doxorubicin (DOX) is a commonly prescribed chemotherapeutic regimen, but its practice is challenged by cardiotoxicity risks. Herbacetin (HBT), a bioactive flavonoid compound, has demonstrated anti-oxidative, anti-inflammation, and anti-tumor properties. This study aimed to evaluate the protective effects of HBT against DOX cardiotoxicity along with the underlying mechanisms. In vitro, HBT enhanced cell survival, prevented DNA damage, reduced mitochondrial ROS, and maintained mitochondrial integrity in DOX-treated cardiomyocytes. Using an acute DOX cardiotoxicity rat model, HBT prevented DOX-induced declined cardiac function and reversed cardiac remodeling depicted by increased cell size. RNA sequence analysis of PBS-, DOX-, and DOX + HBT-treated H9c2 cardiomyocytes suggested the involvement of the MAPK signaling pathway in cardioprotective effects of HBT. Specifically, the level of phosphorylated ERK1/2 was increased in DOX-treated cardiomyocytes, which declined in the presence of HBT. The decreased level of FOXO3a (downstream factor of ERK1/2) by DOX was further restored by HBT. Lastly, the knockdown of FOXO3a abrogated the cardioprotective benefits of HBT. Our data suggest that HBT mitigates acute DOX cardiotoxicity via regulating the ERK1/2-FOXO3a signaling pathway, highlighting its potential as a novel therapeutic agent against DOX cardiotoxicity.
The sialyltransferase ST3GAL1 mediates MUCL1 sialylation to exacerbate breast cancer progression.
Cui C, Feng J, Shang B … +5 more , Guo Q, Wang S, Wang Q, Cheng F, Zhou Y
Hum Cell · 2026 Mar · PMID 41770470 · Publisher ↗
Breast cancer is highly heterogeneous and involves complex molecular mechanisms, posing significant therapeutic challenges. Glycosylation modifications, particularly sialylation, play a critical role in tumor progression...
Breast cancer is highly heterogeneous and involves complex molecular mechanisms, posing significant therapeutic challenges. Glycosylation modifications, particularly sialylation, play a critical role in tumor progression. The sialyltransferase ST3GAL1 is highly expressed in breast cancer, yet its functional interaction with MUCL1 and underlying mechanisms remain elusive. Using in vitro and in vivo models, this study systematically investigated the ST3GAL1-mediated sialylation of MUCL1 and its functional impact on breast cancer progression. The results demonstrated that ST3GAL1 directly binds to MUCL1 and catalyzes its sialylation, thereby increasing MUCL1 protein stability and promoting malignant phenotypes. ST3GAL1 knockdown significantly inhibited cell proliferation, migration, and invasion while inducing apoptosis; its overexpression resulted in the opposite effects. These protumorigenic phenotypes were effectively reversed by treatment with the sialyltransferase inhibitor Lith-O-Asp or MUCL1 knockdown. Moreover, ST3GAL1 knockdown suppressed tumor growth and lung metastasis in vivo. These findings reveal a novel ST3GAL1-MUCL1 regulatory axis that drives breast cancer progression through sialylation, offering a promising target for glycotherapy.
DKK1 exacerbates dental pulp inflammation: insights from RNA-sequencing analysis.
Liang Q, Ding J, Xie J … +3 more , Chen Y, Su W, Liao C
Hum Cell · 2026 Feb · PMID 41758406 · Publisher ↗
Dickkopf-related protein 1 (DKK1) has been implicated in several inflammatory diseases; however, its role in pulpitis remains poorly understood. This study aimed to investigate the role and underlying molecular mechanism...
Dickkopf-related protein 1 (DKK1) has been implicated in several inflammatory diseases; however, its role in pulpitis remains poorly understood. This study aimed to investigate the role and underlying molecular mechanisms of DKK1 on pulpitis using inflamed dental pulp cells (DPCs) as the experimental model. RNA-sequencing (RNA-seq) was conducted on varying concentrations of lipopolysaccharide (LPS)-treated DPCs. Subsequent bioinformatic analyses revealed distinct transcriptional expression patterns between moderate inflammation induced by 1 μg/ml LPS and excessive inflammation induced by 10 μg/ml LPS. Furthermore, the addition of recombinant DKK1 (200 ng/ml) to DPCs treated with 1 μg/ml LPS further enhanced the production of pro-inflammatory cytokines. Bioinformatic analyses based on RNA-seq data identified 24 hub genes in DKK1-stimulated inflamed DPCs, among which the interleukin-17 (IL-17) signaling pathway was the most significantly enriched. Correspondingly, recombinant DKK1 increased the expression of IL-17 receptor in inflamed DPCs. Taken together, these findings indicate that under moderate inflammatory conditions, DKK1 exacerbates inflammation in DPCs through enhancing the production of pro-inflammatory mediators, potentially via modulation of the IL-17 signaling pathway. Thus, targeting DKK1 might have therapeutic potential for promoting the resolution of moderate pulpitis and preventing its severe progression.
MKRN2 enhances hepatocellular carcinoma proliferation through the p38 MAPK pathway.
Chen X, Yan Z, Du X … +7 more , Zhang Z, Liu X, Zhang J, Hu L, He K, Wang J, Han Y
Hum Cell · 2026 Feb · PMID 41741886 · Publisher ↗
Elucidating the molecular mechanisms underlying hepatocellular carcinoma (HCC) pathogenesis is crucial for the development of targeted therapies. Makorin-2 (MKRN2), a member of the makorin RING zinc finger protein family...
Elucidating the molecular mechanisms underlying hepatocellular carcinoma (HCC) pathogenesis is crucial for the development of targeted therapies. Makorin-2 (MKRN2), a member of the makorin RING zinc finger protein family, acts as an E3 ubiquitin ligase that regulates post-translational modifications. Although emerging evidence implicates MKRN2 in the oncogenesis of various malignancies, its biological role in HCC remains poorly characterized. In this study, we found that MKRN2 expression was significantly upregulated in HCC and correlated with poor patient prognosis. To functionally validate the role of MKRN2, we performed CCK-8, colony formation, and EdU assays. Consistently, the results showed that MKRN2 depletion markedly attenuated the proliferative capacity of HCC cells. Subsequently, RNA-seq analysis in Huh-7 cells indicated that MKRN2 was involved in cell cycle regulation and the p38 MAPK signaling pathway. Furthermore, flow cytometry assays demonstrated that MKRN2 depletion arrested the cell cycle at the G1/S transition. Mechanistically, MKRN2 was shown to regulate c-Myc activation via the p38 MAPK pathway, thereby promoting cell cycle progression and enhancing proliferation. In addition, in vivo experiments confirmed that MKRN2 knockdown suppressed tumor growth in xenograft mouse models. In conclusion, our results demonstrate that MKRN2 promotes cell cycle progression and drives proliferation through activation of the p38 MAPK signaling pathway in HCC cells, highlighting its potential as a therapeutic target for HCC.
5-Azacytidine induces sensory hair cell marker expression in human inner ear cells in vitro.
Deng M, Hu Z
Hum Cell · 2026 Feb · PMID 41739281 · Publisher ↗
Adult human inner ear hair cells have extremely limited regenerative ability, and the inaccessibility of human inner ear tissue makes studying regeneration challenging. In this study, we examined whether 5-azacytidine (5...
Adult human inner ear hair cells have extremely limited regenerative ability, and the inaccessibility of human inner ear tissue makes studying regeneration challenging. In this study, we examined whether 5-azacytidine (5-aza) could induce hair cell-like differentiation using our previously established human utricular cell (HUC) line. Our results showed that treatment with 40-80 μM 5-aza was non-toxic, as confirmed by cell counting and calcein/propidium iodide assays. BrdU incorporation analysis showed that fewer treated HUCs entered the S-phase, indicating reduced cell proliferation following 5-aza treatment. Reverse transcription PCR revealed that 5-aza induced the expression of hair cell genes (Myo7a, Pou4f3, Atoh1, and Myo6), which were absent in untreated cells. Immunofluorescence confirmed the expression of hair cell proteins in 5-aza-treated cells, including Myosin VIIa, Pou4f3, Atoh1, Myosin VI, and Calretinin. Additionally, FM1-43 uptake assays indicated the emergence of functional mechanotransduction-like channels in 5-aza-treated HUCs. Together, these results demonstrate that 5-aza reduces proliferation and promotes differentiation of HUCs toward a hair cell-like phenotype. This finding provides new insight into the molecular mechanisms regulating human sensory hair cell differentiation in vitro and highlights the potential of HUCs as a model for studying human inner ear hair cell regeneration.
Establishment and characterization of a novel sinonasal adenosquamous carcinoma cell line, TC717, with a high tumor mutational burden.
Kuga R, Yamamoto T, Iwasaki T … +4 more , Taniguchi M, Manako T, Yamamoto H, Oda Y
Hum Cell · 2026 Feb · PMID 41731210 · Publisher ↗
We established and characterized a novel human sinonasal adenosquamous carcinoma (ASC) cell line, TC717, derived from a 64-year-old, never-smoking woman. The patient received neoadjuvant chemotherapy followed by total ma...
We established and characterized a novel human sinonasal adenosquamous carcinoma (ASC) cell line, TC717, derived from a 64-year-old, never-smoking woman. The patient received neoadjuvant chemotherapy followed by total maxillectomy but succumbed to disease 6 months after therapy initiation. TC717 recapitulated the histologic and immunohistochemical hallmarks of ASC, including squamous differentiation (p40 positivity) and mucin production. The cells displayed a stable doubling time of ~ 27 h. WES revealed a high TMB in both the primary tumor tissue (43.0 mut/Mb) and the TC717 cell line (34.0 mut/Mb), and pathogenic TP53 c.614A > G and BRAF c.1574 T > C variants, neither previously reported in ASC. TC717 provides a valuable preclinical platform for investigating sinonasal ASC biology and for evaluating genotype-directed therapies.
The role of macrophages in peritoneal dialysis-associated peritoneal fibrosis.
Shu J, Sun Z, Zhao W … +2 more , Zhu Y, Wang Q
Hum Cell · 2026 Feb · PMID 41718827 · Publisher ↗
The peritoneum is the largest and most complex serous membrane in the body belonging to the category of semi-permeable membrane. Peritoneal dialysis, which is based on this principle, has become a primary treatment for p...
The peritoneum is the largest and most complex serous membrane in the body belonging to the category of semi-permeable membrane. Peritoneal dialysis, which is based on this principle, has become a primary treatment for patients with end-stage kidney disease. Compared to hemodialysis, peritoneal dialysis is not only simple to operate and less expensive, but also better at preserving residual kidney function. However, peritoneal dialysis-associated fibrosis has become the leading cause of peritoneal function loss and treatment withdrawal. Macrophages play a critical role in the pathogenesis of peritoneal fibrosis. Previous studies have shown that macrophages could affect peritoneal fibrosis through multiple mechanisms, including the activation of signaling pathways in peritoneal mesothelial cells that induce their phenotypic transformation (such as the CX3CL1-CX3CR1 pathway) with mesenchymal cells and the induction of epithelial-mesenchymal transition (EMT). This review summarizes the current understanding of the macrophage-peritoneal fibrosis relationship, providing new ideas for further molecular research, diagnosis, and treatment.
SIRT1 reduced DDX5 neddylation to attenuate myocardial ischemia/reperfusion injury.
Liang Y, Huang G, Zhu X … +3 more , Huang C, Liu H, Shu L
Hum Cell · 2026 Feb · PMID 41667717 · Publisher ↗
BACKGROUND: SIRT1 exhibited a protective role in myocardial ischemia/reperfusion injury (MI/RI), but the related mechanisms remained unclear. In this study, the regulation of SIRT1 on neddylation modification in MI/RI wa...
BACKGROUND: SIRT1 exhibited a protective role in myocardial ischemia/reperfusion injury (MI/RI), but the related mechanisms remained unclear. In this study, the regulation of SIRT1 on neddylation modification in MI/RI was explored. METHODS: H9C2 cells underwent hypoxia and reoxygenation (H/R) to mimic MI/RI in vitro, and C57BL6 mice were employed to establish MI/RI model for the in vivo experiments. Mass spectrometry analysis was employed to screen the possible modified substrates of NEDD8; Western blot was performed to detect protein level; CCK8 was performed to assess cell viability; flow cytometry, TUNEL, and Cardiac Troponin T (cTNT) double staining were performed to assess cardiomyocytes apoptosis; TTC and HE staining were performed to assess infarction area and pathological changes of cardiac tissues in MI/RI mice, respectively. RESULTS: MLN4924 (an inhibitor of NEDD8-activating enzyme (NAE)) significantly reversed the elevated NEDD8 conjugated protein (p < 0.001) and reduced SIRT1 protein levels (p < 0.001) induced by H/R in H9C2 cells. Dead-box helicase 5 (DDX5) was screened as the possible modified substrate of NEDD8 via mass spectrometry. H/R further reduced DDX5 protein level (p < 0.001) and increased DDX5 neddylation in H9C2 cells, while which were reversed by MLN4924 or LV-SIRT1 (p < 0.05). Also, SIRT1 increased DDX5 protein level by enhancing DDX5 stability via reducing its neddylation. Functionally, hypoxia decreased cell viability (p < 0.001) and increased cell apoptosis (p < 0.001) and ROS level (p < 0.001) in H9C2 cells, whereas they were all reversed by LV-SIRT1 (p < 0.05, p < 0.001) or LV-DDX5 (p < 0.05, p < 0.001). The in vivo experiments revealed that LV-DDX5 reversed the increased infarction area (p < 0.05), necrotic myocardial fibers and cardiomyocytes apoptosis (p < 0.001) in MI/RI mice. CONCLUSION: These results suggested that SIRT1 increased DDX5 protein level to reduce cardiomyocytes apoptosis and ROS level via the inhibition of DDX5 neddylation, thus alleviating MI/RI.
Conditioned medium from human adipose-derived mesenchymal stromal cells can modulate cell migration and morphology of keratinocytes in vitro.
Rodrigues C, Paim TC, Zanatelli C … +4 more , Prignon EVS, Azevedo JG, Naasani LIS, Wink MR
Hum Cell · 2026 Feb · PMID 41629724 · Full text
The regenerative ability of the skin is orchestrated by different types of cells, including mesenchymal stromal cells (MSCs). Their role in wound healing is being widely studied due to their capacity to produce a secreto...
The regenerative ability of the skin is orchestrated by different types of cells, including mesenchymal stromal cells (MSCs). Their role in wound healing is being widely studied due to their capacity to produce a secretome able to modulate their microenvironment. In this context, MSCs factors can be isolated using in vitro cell culture and be experimentally tested for a series of clinical conditions, such as skin repair. In this study, we produced conditioned medium (MSC-CM) using primary cultures from human adipose-derived MSCs. This medium was used as treatment in a culture of keratinocytes cell line from adult human skin (HaCaT) to investigate the modulation of their dynamics. We analyzed cell proliferation, migration, and changes on cell morphology by labeling the actin filaments and nuclei. The factors released by MSCs were able to improve both the proliferation and migration of keratinocytes. In addition, there was an increase in the amount of actin stress fibers, filopodia protrusions, and nuclei irregularities. The MSCs secretome modified the migratory patterns of keratinocytes, being observable through their morphological changes. At least in part, this modulation was caused by the TGF-β1 signaling, considering that its antagonist, SB 431542, lead to a reduction of approximately 76% in the migration of HaCaT cells through the porous membranes of transwell chambers. Together, our data contribute to a better understanding of the role of MSCs on keratinocytes during wound healing and reinforce the importance to investigate their potential in dermal regeneration therapies.
The interplay between circadian rhythm components and apoptosis in health and disease.
Khezri MR, Panah SM, Ghasemnejad-Berenji M … +5 more , Ghasemnejad-Berenji H, Mehrzadi S, Fard AA, Rezabakhsh A, Rahnama M
Hum Cell · 2026 Jan · PMID 41619122 · Publisher ↗
In humans, circadian rhythm regulates the expression of numerous protein-coding genes across nearly all cell types, playing a central role in maintaining health. However, circadian rhythm components interact with a wide...
In humans, circadian rhythm regulates the expression of numerous protein-coding genes across nearly all cell types, playing a central role in maintaining health. However, circadian rhythm components interact with a wide variety of intracellular signaling pathways. Through these interactions, the circadian system interfaces with various pathologies by governing different molecular mechanisms. Evidence suggests that the interaction between circadian rhythms and apoptosis plays a pivotal role in both health and disease, warranting careful investigation. Apoptosis, one of the main mechanisms of programmed cell death, is essential for establishing maintaining cellular homeostasis in the human body. Alterations in apoptotic activity occur during the progression of cancer, as well as in various autoimmune and neurodegenerative diseases. Conversely, bidirectional interactions between circadian components and apoptotic factors offer new insights into disease development. Therefore, this review highlights the links between circadian rhythms and apoptosis across health and disease states, aiming to identify potential therapeutic interventions based on this connection.
Construction of a risk model based on exosome-related genes predict clinical prognosis and therapeutic response and revealing TIMP1 as a promising target in colorectal cancer.
Gao X, Zhang T, Li T … +3 more , Zhang Y, Zhang X, Jing H
Hum Cell · 2026 Jan · PMID 41612047 · Publisher ↗
Various exosome-derived proteins have been reported to play essential roles in regulating colorectal cancer progression and affecting the prognosis of cancer patients. It is necessary to explore the critical exosome-rela...
Various exosome-derived proteins have been reported to play essential roles in regulating colorectal cancer progression and affecting the prognosis of cancer patients. It is necessary to explore the critical exosome-related genes in colorectal cancer. In this study, 23 differentially expressed exosome-related genes associated with prognosis in colorectal cancer (CRC) were identified based on two datasets, The Cancer Genome Atlas (TCGA) and exoRbase. Based on machine learning-Boruta and lasso-Cox regression-nine essential genes were finally identified, and a risk model was constructed. The risk model was able to predict the prognosis of the patients well. Specifically, the prognosis of high-risk patients was worse, and the prognosis of low-risk patients was better. Multivariate Cox regression revealed that the risk model was an independent prognostic factor. Mechanism studies showed that pathways such as MYOGENESIS, APICAL JUNCTION, Epithelial-Mesenchymal Transition (EMT), ANGIOGENESIS, and KRAS SIGNALING DN were highly enriched in the high-risk group. In addition, tumor-promoting immune cells, such as Treg cells and macrophages, exhibited increased activity in the high-risk group, suggesting that high-risk patients may be less responsive to immunotherapy. Furthermore, in multiple external immunotherapeutic and chemotherapeutic datasets, we found that high-risk patients are less sensitive to therapy than low-risk patients, suggesting that this risk score may predict immune and chemotherapy response. Scoring the importance of nine genes, we found that TIMP1 was the most critical exosome-related gene in colorectal cancer patients. Knockdown of TIMP1 in colorectal cancer cells significantly inhibited the proliferation and migration of colorectal cancer cells. In conclusion, we identified several crucial colorectal cancer exosome-associated genes using public datasets and machine learning, and constructed risk models to predict prognosis and response to immunotherapy. TIMP1 was further identified as a critical oncogene in patients with colorectal cancer. Our results provide a theoretical basis for subsequent exosome-based preclinical trials.
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