Cell Biology International最新文献

Chronic lung inflammation affects alveolar–capillary permeability and results in impaired gas exchange which may lead to edema, acute lung injury, and acute respiratory distress syndrome. The serine/threonine kinase NEK2, a member of the NIMA-related kinase family, regulates the cell cycle. This kinase was recently implicated in lung inflammation progression since it has been involved in barrier dysfunction and reactive oxygen species generation. This study investigated the effects of a selective NEK2 inhibitor, NCL 00017509, in a murine model of LPS-induced ALI. C57BL/6 male mice received an intratracheal injection of saline or LPS and were post-treated with NEK2 inhibitor or vehicle. Bronchoalveolar lavage fluid (BALF) was collected via tracheal catheterization, and western blot analysis was used to detect protein expression levels. Administration of the NEK2 inhibitor significantly reduced BALF protein concentration, indicating mitigation of lung edema. Moreover, NEK2 inhibition attenuated LPS-induced activation of the JAK/STAT, MAPK signaling, and reduced IL-1α, IL-1β, and IL-17A expression in lung tissues. Furthermore, NEK2 inhibition counteracted LPS-induced Grp94 and BiP suppression. Overall, it is suggested that NEK2 inhibition may alleviate complications related to vascular barrier dysfunction.

Platelet-rich plasma (PRP) contains a complex mixture of growth factors, cytokines, chemokines, miRNAs, hormones and ions that can modulate early reparative events, yet its effects on osteoblastic commitment remain unclear. We examined the transcriptional response of human mesenchymal stem cells (MSCs) exposed for 24 h or 7 d to conditioned media containing PRP or lyophilized PRP (lyPRP), using osteoinductive medium (OM) as positive control. A targeted 48-gene panel spanning differentiation (RUNX2, SP7, ALPL), adhesion/cytoskeleton (ITGB1, PXN, SRC), cell-cycle regulators (CDKs, CDKNs, MKI67) and receptor tyrosine-kinase/PI3K nodes was quantified, with two-way ANOVA testing time and treatment effects; multivariate structure was explored by PCA and correlation networks. PRP and lyPRP consistently upregulated proliferation/viability and adhesion modules - most notably cyclins/CDKs, SRC-axis and selected RTK/PI3K components - while exerting limited induction of canonical osteogenic drivers. Compared with OM, RUNX2, SP7 and ALPL remained lower under PRP or lyPRP, indicating weaker osteoinductive pressure despite preserved metabolic fitness. PCA and network analyses separated PRP/lyPRP from OM, revealing distinct coordination of signaling programs over time. Collectively, PRP and lyPRP favor early proliferative and matrix-interaction states in MSCs but display reduced transcriptional push toward osteogenic differentiation relative to OM. These data support PRP's role in priming cellular proliferation and microenvironmental readiness while underscoring the need for dosing, timing and formulation strategies if osteoinduction is the therapeutic goal.

Endometriosis (EMS), a multifactorial and chronic benign gynecological disease characterized by ectopic endometrial growth, remains poorly understood in its pathogenesis. Proline, glutamic acid, leucine-rich protein 1 (PELP1), implicated in various diseases, has not been studied in EMS. Here, we investigated the functional role and molecular mechanisms of PELP1 in EMS progression. Using ectopic and eutopic endometrial tissues from EMS patients, we showed that PELP1 was significantly upregulated in ectopic lesions. Knockdown of PELP1 in primary ectopic endometrial stromal cells (Ec-ESCs) and the mouse model inhibited proliferation, angiogenesis, and inflammation. Mechanistically, PELP1 interacted with FHL2 to potentiate transcriptional activation of downstream factors, such as CCND1, CCND2, CDK6, ANG, CCL2, and MMP3. These findings demonstrate that PELP1 promotes EMS progression and highlight its potential as a novel therapeutic target.

Sodium tanshinone IIA sulfonate exerts several pharmacological effects; however, its mechanism in skeletal muscle injuries remains unknown. We explored the biological function of sodium tanshinone IIA sulfonate in skeletal muscle injury and elucidated its underlying mechanisms. We established a skeletal muscle injury model following blunt trauma and transforming growth factor-β1-induced NIH/3T3 cell models. Morphological changes, collagen deposition, and fibrosis in the muscle tissues were evaluated, and cell proliferation was determined. The expression of myogenic differentiation markers in C2C12 cells, including myogenic differentiation 1 and myosin heavy chain, and the activity of the transforming growth factor-β1/Smad3 and phosphoinositide 3-kinase/protein kinase B/cyclooxygenase-2 signaling pathway were measured. Compared to the model group, the sodium tanshinone IIA sulfonate-treated group showed reduced inflammatory cell infiltration, collagen deposition, and fibrosis. Transforming growth factor-β1 and cyclooxygenase-2 expression and Smad3 and phosphoinositide 3-kinase/protein kinase B pathway activation were inhibited by sodium tanshinone IIA sulfonate. In vitro, sodium tanshinone IIA sulfonate treatment significantly reduced NIH/3T3 cell proliferation and downregulated p-Smad3, transforming growth factor-β1, and cyclooxygenase-2 expression in a dose-dependent manner. Moreover, sodium tanshinone IIA sulfonate enhanced myogenic differentiation 1 and myosin heavy chain expression in C2C12 cells. Furthermore, sodium tanshinone IIA sulfonate inhibited the activation of transforming growth factor-β1/Smad3 and phosphoinositide 3-kinase/protein kinase B/cyclooxygenase-2 signaling pathway in skeletal muscle fibrosis. Thus, sodium tanshinone IIA sulfonate exerted a suppressive effect on skeletal muscle fibrosis via the transforming growth factor-β1/Smad3 and phosphoinositide 3-kinase/protein kinase B/cyclooxygenase-2 signaling pathways, providing a new therapeutic approach for skeletal muscle fibrosis.

Dysregulation of epoxide hydrolase 2 (‌EPHX2) is associated with the pathogenesis of various diseases. However, the functional role of EPHX2 in ulcerative colitis remains unclear. In this study, we demonstrate that EPHX2 plays a critical role in driving the pathological breakdown of barrier integrity in a colitis model. Pharmacological inhibition of EPHX2 significantly ameliorated Dextran Sulfate Sodium (DSS)-induced colitis. Notably, conditional knockout of EPHX2 in intestinal epithelial cells (IECs) conferred protection against colitis-associated mucosal damage. Moreover, EPHX2 deletion in IECs led to increased Muc2 expression and a higher number of goblet cells by promoting goblet cell differentiation, while the expression levels of tight junction proteins (ZO-1, occludin, and claudin-1) remained unchanged. These findings identify a previously unrecognized role of EPHX2 in IECs and suggest that targeting EPHX2 may represent a promising therapeutic strategy for ulcerative colitis.

Melasma and other hyperpigmentation disorders represent a significant challenge in dermatology. Tranexamic acid (TXA), traditionally known for its antifibrinolytic activity via inhibition of plasminogen activation, has recently emerged as a promising depigmenting agent. However, its cellular effects on skin cells involved in melanogenesis remain poorly understood. In this study, we investigated TXA's impact on melanocytes, keratinocytes, and inflammatory cells. TXA directly inhibited melanin synthesis in B16 melanoma cells, with an additive effect when combined with α-arbutin. In keratinocytes and macrophages, TXA attenuated inflammatory responses triggered by the plasminogen/plasmin (Plg/Plm) pathway. Moreover, TXA reduced lipopolysaccharide-induced pro-inflammatory gene expression in mouse macrophages, suggesting interference with Toll-like receptor-mediated inflammation. These findings highlight TXA's multifaceted actions on skin cells involved in pigmentation and support its therapeutic potential in melasma and potentially other skin diseases.

Renal fibrosis driven by TGF-β/Smad3 signaling is a critical factor in the advancement of chronic kidney disease, and partial epithelial-to-mesenchymal transition (EMT) in tubular cells plays a significant role in this process. In this study, we explored the reno-protective role of biochanin A (BCA), a natural isoflavone, in mice with unilateral ureter obstruction (UUO) and in cultured renal tubular TCMK1 cells stimulated with the profibrotic cytokine TGF-β1. Our results demonstrated that BCA (20 and 50 mg/kg) dose-dependently ameliorated structural damage in UUO kidneys with reduced extracellular matrix deposition and downregulated levels of fibrotic genes Col1a1, fibronectin, and α-SMA. In vitro, BCA (5 and 10 μg/mL) also exhibited a dose-dependent anti-fibrosis effect in TCMK1 cells induced by TGF-β1. Moreover, BCA prevented tubular partial EMT by mitigating the upregulation of mesenchymal marker genes N-cadherin and vimentin in UUO kidneys and TGF-β1-induced TCMK1 cells. BCA treatment also reversed the reduced staining of Lotus Tetragonolobus Lectin and peanut agglutinin, two markers of mature renal tubular epithelia, in UUO kidneys. Mechanistically, BCA inhibited Smad2 and Smad3 phosphorylation and specifically downregulated Smad3 protein expression, without affecting Smad2, in TGF-β1-stimulated TCMK1 cells. Most importantly, in TGF-β1-treated TCMK1 cells, Smad3 overexpression abolished the anti-fibrosis and anti-EMT effects of BCA. In conclusion, our findings demonstrate the potential of BCA as a therapeutic agent against renal fibrosis by inhibiting TGF-β/Smad3 signaling-mediated tubular partial EMT.

Gastric cancer (GC) is one of the most prevalent malignant tumors worldwide, with limited treatment efficacy and high drug resistance. Natural compounds offer promising therapeutic potential due to their multitarget and low-toxicity profiles. This study aimed to explore the anticancer effects of Oroxin A (OA), a natural flavonoid, and its underlying mechanisms in gastric cancer. A series of in vitro assays and organoid models were used to assess OA's effects on cell viability, proliferation, and migration. Mechanistic investigations included RNA-sequencing, Western blot analysis, immunofluorescence, and electron microscopy. OA significantly inhibited gastric cancer cell growth and migration while showing minimal toxicity to normal gastric epithelial cells. OA induced autophagic, rather than apoptotic, cell death. Mechanistically, OA activated the MAPK/ERK signaling pathway, upregulated REDD1, and inhibited mTOR signaling, leading to enhanced autophagy. REDD1 overexpression amplified this effect, whereas knockdown reversed it. OA induces autophagic cell death in gastric cancer cells via the MAPK/ERK/REDD1 pathway, providing a promising natural compound candidate for gastric cancer therapy.

Glioblastoma is the most aggressive type of brain tumor, with a dismal prognosis, highlighting the urgent need for novel biomarkers and therapeutic targets. Recent advances in transcriptomics and proteomics have revealed the critical role of small open reading frame (sORF)-encoded micropeptides, a previously overlooked class of polypeptides derived from noncoding RNAs (ncRNAs), in glioblastoma pathogenesis. In this review, the current knowledge on the functional mechanisms of these micropeptides—including MP31, SHPRH-146aa, AKT3-174aa, and others—which regulate tumor metabolism, proliferation, angiogenesis, and therapeutic resistance, is synthesized. These micropeptides act as molecular switches by modulating key pathways or stabilizing tumor-suppressive proteins. We outline methods for identifying sORFs and validating their translation potential and functional characteristics. Emerging evidence highlights their diagnostic and prognostic value, as well as their therapeutic potential as peptide-based drugs or targets for precision oncology. Despite the challenges in detecting low-abundance micropeptides, their specificity and functional diversity make them promising candidates for improving glioblastoma management. Future studies should prioritize clinical translation and mechanistic exploration to harness their full potential in combating this lethal disease.