Cardiac fibrosis is a prevalent pathological feature in the progression of various cardiovascular diseases, including heart failure, myocardial infarction, and dilated cardiomyopathy, particularly in their advanced stage...Cardiac fibrosis is a prevalent pathological feature in the progression of various cardiovascular diseases, including heart failure, myocardial infarction, and dilated cardiomyopathy, particularly in their advanced stages. Its primary mechanism involves the abnormal activation of cardiac fibroblasts and excessive deposition of extracellular matrix, which ultimately results in decreased myocardial compliance and cardiac dysfunction. The Hippo signaling pathway, an evolutionary conserved kinase cascade, not only regulates organ development and tissue homeostasis but has also been shown to play a critical role in cardiac fibrosis. Notably, the Hippo pathway demonstrates cell-specific regulatory functions across different cardiac cell types, including cardiomyocytes, fibroblasts, and immune cells. This systematic review elucidates the molecular mechanisms by which the Hippo pathway influences cardiac fibrosis, emphasizing its cell type-dependent roles. It analyzes the complexity of its roles from the perspectives of cross-talk between pathways, various types of cardiac diseases, and different stages of disease progression. Additionally, it summarizes recent advancements in anti-fibrotic drugs that target this pathway, thereby providing a theoretical foundation for the development of novel therapeutic strategies in cardiac fibrosis.
Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related mortality worldwide, with poor prognosis largely attributed to late-stage diagnosis and therapeutic resistance. Cisplatin (DDP) resistance is a majo...Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related mortality worldwide, with poor prognosis largely attributed to late-stage diagnosis and therapeutic resistance. Cisplatin (DDP) resistance is a major challenge in NSCLC treatment. Emerging evidence highlights the critical role of N6-methyladenosine (m6A) RNA modification in regulating cancer progression and drug resistance, with methyltransferase-like 3 (METTL3) serving as the key methyltransferase mediating m6A deposition on RNAs. In this study, we investigated the role of the circular RNA hsa_circ_0003176 in DDP-resistant NSCLC and its regulation by m6A modification. We found that hsa_circ_0003176 was significantly downregulated in DDP-resistant NSCLC cells and functioned as a tumor suppressor by promoting autophagy, inhibiting glycolysis, and reversing DDP resistance. Mechanistically, METTL3-mediated m6A modification suppressed hsa_circ_0003176 expression, while hsa_circ_0003176 directly targeted and destabilized ribosomal protein S6 kinase B1 (RPS6KB1) mRNA, a key regulator of mTORC1 signaling, thereby inhibiting NSCLC progression. In addition, in vivo xenograft models confirmed that hsa_circ_0003176 overexpression suppressed tumor growth and enhanced DDP sensitivity. Our study reveals the METTL3/m6A/hsa_circ_0003176/RPS6KB1 pathway as a critical pathway in NSCLC chemoresistance, offering novel therapeutic targets for overcoming DDP resistance.
Ethambutol (EMB)-induced optic neuropathy (EON) is a clinical concern. Ferroptosis, involving iron and toxic reactive oxygen species (ROS), causes unique cell death, but its mechanism in EON is unclear. This study aims t...Ethambutol (EMB)-induced optic neuropathy (EON) is a clinical concern. Ferroptosis, involving iron and toxic reactive oxygen species (ROS), causes unique cell death, but its mechanism in EON is unclear. This study aims to explore the EON mechanisms. Wistar rats were used to establish an EON model by administering EMB at 50 mg/kg daily for 8 weeks. Retinal ganglion cells (RGC-5 cells) were used for in vitro experiments. Histological staining, MTT assays, flow cytometry, western blot analysis, dual-luciferase reporter assay, chromatin immunoprecipitation, and high-throughput sequencing were conducted to investigate cell death modes and molecular changes. EMB treatment leads to significant cell loss and structural damage in RGCs of EON model, predominantly through ferroptosis. We confirm increased ROS levels, downregulation of SLC7A11 and GPX4, and decreased glutathione (GSH) levels, upregulation of malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) levels in EMB-treated RGC-5 cells. Furthermore, sequencing data reveal that in RGC-5 cells treated with EMB, the differentially expressed genes (DEGs) primarily exhibited alterations in biological functions associated with metabolism, stress response, and apoptotic regulation. Specifically, EMB inhibits the expression of succinate dehydrogenase enzyme B (SDHB), thereby disrupting antioxidant defenses and facilitating ferroptosis. Moreover, Smad4 has been pinpointed as a pivotal transcription factor in regulating SDHB expression. Notably, its interaction with the promoter region of SDHB is inhibited by EMB. This study provides compelling evidence for the involvement of ferroptosis in EON and highlights SDHB and Smad4 as potential therapeutic targets for mitigating this adverse effect.
Lung adenocarcinoma (LUAD), the most prevalent and aggressive form of non-small cell lung cancer. Natural compounds have gained increasing attention as potential anti-cancer agents. The therapeutic potential of chebulagi...Lung adenocarcinoma (LUAD), the most prevalent and aggressive form of non-small cell lung cancer. Natural compounds have gained increasing attention as potential anti-cancer agents. The therapeutic potential of chebulagic acid (CA)-a hydrolysable tannin with documented anti-proliferative properties-has not been investigated in LUAD. In the present study, functional experiments revealed that CA treatment markedly suppressed proliferation and induced mitochondrial-dependent apoptosis of LUAD cells. In addition, CA augments natural killer (NK) cell migration by enhancing LUAD CCL5 production. Quantitative proteomics identified FBXO38 as the most significantly upregulated protein following CA treatment. FBXO38 silencing abrogated CA-induced CCL5 production and NK cell migration in LUAD cells. The in vivo experiments showed that CA significantly inhibited tumor growth and enhanced NK cell infiltration in mice, accompanied by decreased Ki67 proliferating cells, increased cleaved caspase-3 apoptotic cells, and upregulated FBXO38 expression. Collectively, our findings demonstrate that CA may be exert anti-LUAD effects through FBXO38/CCL5-mediated NK cell recruitment.
The growth of human pulmonary arterial smooth muscle cells (hPASMCs) is one of the key contributors to vascular remodeling in pulmonary arterial hypertension (PAH). Although histone deacetylase 3 (HDAC3) has been implica...The growth of human pulmonary arterial smooth muscle cells (hPASMCs) is one of the key contributors to vascular remodeling in pulmonary arterial hypertension (PAH). Although histone deacetylase 3 (HDAC3) has been implicated in acute lung injury and pulmonary fibrosis, its role in hypoxia-induced PAH remains unclear. Here, the function and associated mechanisms of HDAC3 in hypoxia-induced hPASMC proliferation were investigated. A hypoxia-induced hPASMC model was constructed to evaluate the role of HDAC3 in cell proliferation under hypoxic conditions. The effects of HDAC3 siRNA and ruxolitinib, a JAK pathway inhibitor, were assessed to explore the regulatory mechanism of HDAC3 in vascular remodeling. Hypoxia significantly upregulated both HDAC3 mRNA and protein. Inhibition of HDAC3 attenuated hypoxia-induced proliferation in hPASMCs. Moreover, HDAC3 inhibition downregulated CSF2 and suppressed proliferation by inactivating the JAK2/STAT5 axis. In contrast, HDAC3 overexpression enhanced CSF2 expression, activated JAK2/STAT5, and promoted hPASMCs' proliferation under hypoxia. Notably, the pro-proliferative and pathway-activating effects of HDAC3 overexpression were reversed by CSF2 silencing or ruxolitinib treatment. HDAC3 plays a key role in hypoxia-induced hPASMC dysfunction. Its inhibition mitigates aberrant proliferation through a CSF2-dependent inactivation of the JAK2/STAT5 pathway under hypoxia. These results indicate the potential of using HDAC3 for treating hypoxia-induced PAH.
Hydatidiform mole (HM) is a pathological pregnancy characterized by excessive trophoblast proliferation and the absence of embryonic tissue development, predominantly sporadic in onset. Recurrent hydatidiform mole (RHM)...Hydatidiform mole (HM) is a pathological pregnancy characterized by excessive trophoblast proliferation and the absence of embryonic tissue development, predominantly sporadic in onset. Recurrent hydatidiform mole (RHM) affects approximately 1%-4% of HM patients, among which familial RHM (FRHM) is extremely rare and classified as a monogenic autosomal recessive disorder. NLRP7 (NLR family, pyrin domain containing 7) is the major pathogenic gene for RHM, in which affected individuals have a profound impairment in fertility and a markedly elevated risk of malignant transformation. Yet mechanistic research remains constrained by ethical limitations in human embryo studies and the absence of animal models recapitulating HM phenotypes. Here, we report the generation and characterization of iPSC lines from FRHM patients harboring homozygous NLRP7 variants c.2078G > A (p.Arg693Gln) and c.2161 C > T (p.Arg721Trp), respectively. These cellular models offer a unique platform to dissect molecular pathways driving NLRP7-mediated reproductive failure, overcoming long-standing barriers in FRHM pathogenesis research.
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 v...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 fun...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 potenti...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% O) 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.
Nakayama A, Hayano K, Ueno M
… +21 more, Miyoshi Y, Nakashima H, Shimizu S, Hashimoto I, Toba M, Kikuchi R, Takehana N, Miura M, Kawamura Y, Toyoda Y, Mizuno T, Tanabe R, Hamada Y, Tamura T, Kato Y, Mitsuda Y, Nakaoka H, Yamamoto K, Tsunoda M, Shinomiya N, Matsuo H
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 (polymorphism...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 progres...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....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 macroph...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...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. Dysregul...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.
The objective of this research was to investigate the effects of proven antioxidant compounds identified in Nitraria retusa leaf extracts (Nr-extracts) on glioblastoma (GBM) cells. The antioxidant capacity was evaluated...The objective of this research was to investigate the effects of proven antioxidant compounds identified in Nitraria retusa leaf extracts (Nr-extracts) on glioblastoma (GBM) cells. The antioxidant capacity was evaluated in nonenzymatic, enzymatic, and cellular systems. The antitumoral effect was demonstrated first by studying the inhibition of glioblastoma cell growth, then by examining the inhibition of cell adhesion to various purified extracellular matrix (ECM) proteins, and finally by assessing the ability of Nr-extracts to abolish the invasion of collagen gel by human glioblastoma cell spheroids. The methanolic extract (Nr-MeOH), through its isorhamnetin and carbohydrate derivatives, showed the highest antioxidant capacity. The cytotoxicity study of Nr-extracts, in the absence and presence of TEMODAL (TPZ), revealed that the chloroform extract (Nr-Chl), through its β-sitosterol and in combination with TEMODAL, exerted a more significant apoptotic effect on glioblastoma cells than TEMODAL alone. However, only the Nr-Chl and Nr-MeOH extracts inhibited the attachment of U87 cells to fibronectin, vitronectin, and collagen I. In addition, Nr-MeOH more significantly reduced U87 cell invasion compared with Nr-Chl extract. In conclusion, flavonols and sterols demonstrated strong antitumoral and free radical-scavenging activities, suggesting that a potentially synergistic therapeutic approach for glioma can be developed.
George A, Nair S, Prabhash K
… +13 more, Thakur S, Gera P, Singh A, Chaturvedi P, Rane S, Pradhan T, Sen S, Barkume M, Shetty D, Chaubal K, Ghosh A, Kamte S, Kode JA
Being topmost cancer in India, oral cancer management warrants discovery of novel biomarkers, treatment strategies, and targets to help with early diagnosis, treatment, and recovery. To have a continuous supply of cells,...Being topmost cancer in India, oral cancer management warrants discovery of novel biomarkers, treatment strategies, and targets to help with early diagnosis, treatment, and recovery. To have a continuous supply of cells, the study was aimed at generation and characterization of established cell line from buccal mucosa (BM) tumors from patients of Indian origin which can be developed as a pre-clinical tool for biomedical application. Surgically resected tumor tissue from histo-pathologically confirmed oral cancer were processed for explant culture. TBM-02 cell line was passaged and characterized for morphology and function. Further, the cell line was silenced for inflammasome pathway gene NLRP3 to evaluate its linkage with oral cancer tumorigenesis. TBM-02, successfully established from BM, was maintained up to 100 passages, exhibited epithelioid morphology, high EpCam expression and triploid ploidy with chromosomal aberrations. Novelty and human origin of TBM-02 was authenticated by Short Tandem Repeats profiling and comparison with DSMZ database. TBM-02 revealed tumorigenic potential in vitro and in vivo which was abrogated on silencing NLRP3. Increased expression of NLRP3, hallmark of chronic inflammation in TBM-02, was validated at protein and gene level and in xenograft. TBM-02 demonstrated migratory potential and was found to be a sensitive tool to study drug response. RNA sequencing demonstrated upregulation of oral cancer-associated genes and pathways. Thus, in current study, we have reported development of novel cell line from early-stage buccal mucosa cancer patient which has a strong potential to be developed and to be used as pre-clinical model for improving oral cancer management and therapeutics.
Circular RNAs (circRNAs) are involved in cardiovascular disease development and progression. We identified has_circ_0000437 from three pairs of clinical samples using a circRNA microarray and predicted the has_circ_00004...Circular RNAs (circRNAs) are involved in cardiovascular disease development and progression. We identified has_circ_0000437 from three pairs of clinical samples using a circRNA microarray and predicted the has_circ_0000437 sponge let-7f-5p using bioinformatics. We expanded the sample to confirm the expression, correlation, and diagnostic value of has_circ_0000437, let-7f-5p and RAS-like proto-oncogene B (RALB) in rheumatic valvular heart disease (RVHD). The effects of has_circ_0000437 and let-7f-5p on biological function were observed in hVICs cells. To explore the molecular pathogenesis of has_circ_0000437 in the RVHD process, the target binding protein RAS-like proto-oncogene B (RALB) of has_circ_0000437 was obtained using label-free mass spectrometry and parallel reaction monitoring. The influence of the has_circ_0000437/let-7f-5p/RALB axis on the expression of mitogen-activated protein kinase (MAPK)-related proteins in the inflammatory signaling pathway predicted by Kyoto Encyclopedia of Genes and Genomes (KEGG) during RVHD was measured using Western blotting. We found that let-7f-5p was at low expression and negatively correlated with has_circ_0000437, which had a diagnostic value with an area under the curve of 0.998 after the combined diagnosis. Has_circ_0000437 and let-7f-5p had binding sites, and let-7f-5p alleviated the effect of has_circ_0000437 on the proliferation, migration, and cycle progression of hVICs. The inhibitory effect of has_circ_0000437 on hVICs apoptosis was diminished. Mechanism studies showed that has_circ_0000437 promotes the MAPK pathway through has_circ_0000437/let-7f-5p/RALB axis. These findings suggest that the has_circ_0000437/let-7f-5p/RALB axis promotes the MAPK pathway, proliferation, migration, and cycle progression in RVHD, inhibiting the apoptosis process, thereby promoting RVHD development. This pathway may suggest a target for RVHD diagnosis and treatment.