Cell Biochemistry and Biophysics最新文献

Endometrial cancer is a prevalent type of cancer among women worldwide. The irregularity of the PI3K/AKT/mTOR signaling pathway plays a role in the pathogenesis of many cancer types. MicroRNAs are small noncoding RNAs that play crucial roles in the pathogenesis of different cancer types. MicroRNAs target many key components of the PI3K/AKT/mTOR pathway in human tumors. In this study the PI3K/AKT/mTOR pathway was affected in endometrial cancer, and the expression levels of miR-7, miR-17, miR-145, miR-155, miR-206, miR-221, miR-222 were determined. In addition, in silico analyses were examine the molecular interactions between miRNAs and target genes. Identifying dysregulated miRNA expression in endometrial cancer is important for developing miRNA-based therapeutic strategies. In our study, Grade 1 (n = 16), Grade 2 (n = 16), Grade 3 (n = 16), tissues diagnosed with endometrioid adeno carcinoma, control 1 (n = 16) secretory phase and control 2 (n = 16) proliferative phase healthy endometrial tissues without endometrial cancer were included. miRNA expression analysis was performed using the real-time PCR. In our study, the expression of miR-7-5p, miR-145-5p, and miR-206 decreased, whereas the expression of miR-17-5p, miR-221-3p, and miR-222-3p increased in endometrial cancer (p < 0,05). Statistically significant results were not obtained to for the expression levels of miR-21-5p and miR-155-5p. miR-7-5p targets PIK3CD, PIK3R3, PIK3CB and AKT3, miR-17-5p targets PIK3R1 and AKT3, miR-21-5p target PIK3R1, miR-145-5p target AKT3, miR-155-5p targets PIK3CA and PIK3R1, miR-206 target PIK3C2A, miR-221-3p and miR-222-3p target PIK3R1 as identified via in silico analysis. These results can shed light on the development of molecular-targeted therapy strategies. Treatment strategies can be developed by designing ASOs, LNAs, miRNA antagomirs, or miRNA sponges for upregulated miR-17-5p, miR-221-3p, and miR-222-3p, and miRNA mimics for downregulated miR-7-5p, miR-145-5p, and miR-206.

Prostate cancer (PCa) is a major cause of cancer-related mortality in men. This study explores the anticancer potential of Quercetin, a polyphenolic compound with antioxidant and anti-inflammatory properties, by network pharmacology, molecular docking, and molecular dynamics simulation approaches. Target genes for Quercetin and PCa were identified from the bioinformatics databases MalaCards, Comparative Toxicogenomics Databases, SwissTargetPrediction, and Traditional Chinese Medicine Systems Pharmacology, and the obtained genes were matched using the Venny platform to find out the common genes. We obtained 11 preliminary genes and analyzed them in ShinyGO-0.77 databases to obtain genetic otology data. Then, we constructed a protein-protein interaction network in STRING, which enabled us to identify six hub genes AKT1, EGFR, MMP2, MMP9, PARP1, and ABCG2. Hub genes were analyzed in the TISIDB database for immune cell infiltration. Furthermore, a molecular docking study between the target proteins and Quercetin was performed in the SwissDock databases. Subsequently, we corroborated the docking with molecular dynamics studies using GROMACS software. Gene Ontology and KEGG pathway analyses revealed that Quercetin influences oxidative stress, mitochondrial function, and metalloproteinase activity. Immune cell infiltration analysis highlighted correlations between key genes and specific immune responses, suggesting a modulatory role of Quercetin in the tumor microenvironment. Finally, docking and molecular dynamics analysis showed that Quercetin has a stable interaction with the hub genes. In conclusion, these findings underline the potential of Quercetin to induce apoptosis, inhibit angiogenesis, and suppress metastasis, proposing it as a promising therapeutic tool for the treatment of PCa. However, additional experimental studies are required to translate these findings into clinical practice.

Idiopathic Pulmonary Fibrosis (IPF) is a severe, rapidly advancing disease that drastically diminishes life expectancy. Without treatment, it can progress to lung cancer. The precise etiology of IPF remains unknown, but inflammation and damage to the alveolar epithelium are widely thought to be pivotal in its development. Research has indicated that activating the NLRP3 inflammasome is a crucial mechanism in IPF pathogenesis, as it triggers the release of pro-inflammatory cytokines such as IL-1β, IL-18, and TGF-β. These cytokines contribute to the myofibroblast differentiation and extracellular matrix (ECM) accumulation. Currently, treatment options for IPF are limited. Only two FDA-approved medications, pirfenidone and nintedanib, are available. While these drugs can decelerate disease progression, they come with a range of side effects and do not cure the disease. Additional treatment strategies primarily involve supportive care and therapy. Emerging research has highlighted that numerous flavonoids derived from traditional medicines can inhibit the critical regulators responsible for activating the NLRP3 inflammasome. These flavonoids show promise as potential therapeutic agents for managing IPF, offering a new avenue for treatment that targets the core inflammatory processes of this debilitating condition.

Chronic Kidney Disease (CKD) is an irreversible pathological condition resulting from the gradual accumulation of nephrotoxic substances. The application of the "Kidney Toxicity" theory in CKD treatment holds significant research potential and promising clinical prospects. We established a murine model of unilateral ureteral obstruction (UUO) and administered the traditional Chinese medicine prescription Suyin detoxification prescription (SDP). The efficacy of SDP was assessed by comparing the expression levels of Klotho, NF-κB, pNF-κB, VEGF, α-SMA, pERK1/2, and ERK1/2 proteins with those in the Sham operation group using immunohistochemistry, RT-qPCR, and Western Blot techniques. The study revealed a significant reduction in the expression of Klotho and VEGF proteins during the progression of renal fibrosis in mice, while there was a marked increase in the levels of pNF-κB, α-SMA, and pERK1/2 proteins, demonstrating statistical significance (p < 0.05). In UUO mice treated with a high dose of SDP, these proteins exhibited an opposite expression trend compared to that observed in pure operated model mice, with statistically significant differences (p < 0.05). Subsequently, we investigated the relationship between Klotho protein and the ERK/NF-κB signaling pathway-related proteins in human umbilical vein endothelial cells (HUVECs). Knockdown of Klotho protein in HUVECs confirmed its potential as a target for SDP's renal protective effects in vivo by regulating ERK/NF-κB signaling pathway-related proteins to some extent. The renoprotective effect of SDP is mediated through modulation of Klotho protein expression in renal tissues, thereby influencing the ERK/NF-κB signaling pathway and ameliorating the inflammatory processes associated with renal fibrosis. The present study has significantly contributed to the advancement and refinement of the pathogenesis of "Kidney Toxicity" as well as the therapeutic approach of "Kidney Detoxification".

Acute myeloid leukemia (AML) is a challenging hematologic malignancy with a poor prognosis. STYX, a catalytically inactive phosphatase, is overexpressed in various cancers and has been shown to promote cellular proliferation. However, its clinical relevance and impact on AML cell behavior remain poorly understood. This study investigates the role of STYX in AML and elucidates its underlying molecular mechanisms. Peripheral blood samples were collected from 50 patients with AML and 25 healthy controls, and the expression of STYX and FBXW7 was analyzed using RT-qPCR and Western blot. THP-1 cells (AML cell line) were transfected with lentivirus vectors to overexpress STYX, FBXW7, or CCNE1. The effects of these proteins on THP-1 cell proliferation and apoptosis were assessed by RT-qPCR, Western blot, CCK-8, EdU, and TUNEL assays. Interactions between STYX and FBXW7, as well as FBXW7 and CCNE1, were confirmed via STRING analysis and endogenous co-immunoprecipitation (CO-IP). Furthermore, the ubiquitination level of CCNE1 was examined through immunoprecipitation (IP) and Western blot. Upregulated STYX mRNA and protein levels, along with downregulated FBXW7 mRNA and protein levels, were observed in peripheral blood samples from MLL-AF9 fusion gene-positive AML cases, with a negative correlation between STYX and FBXW7. Overexpression of STYX in AML cells increased cell viability, promoted proliferation, and inhibited apoptosis, thus accelerating AML progression. STYX overexpression also facilitated the interaction with FBXW7, downregulated FBXW7 expression, and impaired the ubiquitin-mediated degradation of CCNE1. FBXW7 overexpression reversed STYX-induced proliferation and apoptosis effects in AML cells, while CCNE1 overexpression counteracted the suppressive effects of FBXW7 on AML progression. STYX promotes AML proliferation by disrupting the ubiquitin degradation pathway of CCNE1 through its interaction with FBXW7, thereby accelerating disease progression. These findings indicate that targeting STYX may offer a promising therapeutic approach for AML.

Epithelial-mesenchymal transition (EMT) induced by transforming growth factor-β (TGF-β) is involved in hepatocellular carcinoma (HCC) growth and metastasis. Our study aimed to investigate the role of molecules interacting with CasL 1 (MICAL1) in regulating TGF-β-triggered EMT in HCC and the related mechanisms. After detecting MICAL1 expression and prognostic value in HCC, in vitro assays including CCK-8 assay, EdU staining, flow cytometry assay, Transwell assay, western blotting, and RT-qPCR and in vivo metastasis assay was conducted to evaluate the influence of MICAL1 knockdown on the proliferation and apoptosis as well as TGF-β-induced EMT and metastasis of Huh7 and MHCC97H cells. MICAL1 was highly expressed in HCC, and its high expression was related to histological grade, TNM stage, and shorter overall survival of HCC patients. MICAL1 silencing suppressed proliferation, promoted apoptosis, and curbed TGF-β1-triggered cytoskeletal remodeling, EMT, and metastasis of HCC cells. MICAL1 knockdown impeded TGF-β1-induced upregulation in phosphorylated-Smad2/3 protein levels and reduced Smad2/3 mRNA levels in HCC cells. MICAL1 downregulation enhanced the polyubiquitination and proteasomal degradation of TβRI. Additionally, MICAL1 silencing suppressed tumor growth and lung metastasis in Huh7-derived xenograft mouse models. Collectively, MICAL1 knockdown impairs TGF-β1-stimulated EMT and metastasis of HCC cells by restraining Smad2/3 phosphorylation and activation.

Acute kidney injury (AKI) and acute lung injury (ALI) are major complications of intra-abdominal sepsis, leading to increased mortality. Phellodendrine (PHE) is a characteristic and important active ingredient of Phellodendri Cortex, possessing multiple pharmacological properties. This study intends to explore the effect of PHE on intra-abdominal sepsis-induced AKI and ALI. An intra-abdominal infection-induced rat model of sepsis was established by fecal intraperitoneal injection, followed by the administration of PHE. ELISA was used to determine plasma levels of inflammatory cytokines. Hematoxylin-eosin, Periodic acid Schiff, and Masson trichrome staining were employed for histopathological analysis of rat kidney and lung tissues. Western blotting was used to estimate the AKT/NF-κB signaling-related protein levels. The results showed that PHE improved the survival rate of septic rats and reduced plasma levels of proinflammatory cytokines. PHE administration attenuated pathological lesions in the kidneys and lungs of septic rats. Mechanistically, PHE treatment blocked AKT/NF-κB signaling in septic rats' kidneys and lungs. In conclusion, PHE ameliorates intra-abdominal sepsis-induced kidney and lung injury possibly by inactivating AKT/NF-kB signaling.

To investigate the effects and potential mechanism of miR-634 that regulates aquaporin 5 (AQP5) to regulate the inflammatory response and apoptosis in LPS-induced human nasal epithelial cells (HNEpCs). The mRNA expressions of miR-634 and AQP5 in the tissues of patients with chronic rhinosinusitis (CRS) and LPS-induced HNEpCs were detected by qRT-PCR. Western blotting was performed to detect the protein expression of AQP5 in HNEpCs. The apoptosis was assessed by flow cytometry. The cell viability was detected by CCK-8 kit. Combined with bioinformatics analysis, dual-luciferase reporter and western blotting, the interaction between AQP5 and miR-634 were predicted and verified. It proved that the mRNA expression of miR-634 in CRS group was significantly up-regulated, while AQP5 was down-regulated. And the expression of AQP5 in CRS group was down-regulated compared with control group. In vitro experiments indicated that the expression of miR-634 increased gradually, while AQP5 decreased gradually with the increase of LPS concentration. The cell viability was inhibited and apoptosis was promoted in LPS-induced group. In addition, it was found that miR-634 could inhibit cell viability and promote apoptosis. QRT-PCR results implied that miR-634 up-regulated the expression of inflammatory factor-related mRNA in LPS-induced HNEpCs. Combined with bioinformatics analysis and qRT-PCR, it was confirmed that AQP5 was the direct target of miR-634. MiR-634 directly targeted AQP5 to regulate CRS progression, including inhibiting cell viability, promoting apoptosis and aggravating inflammatory response, which may provide theoretical basis for its use as a biomarker for CRS treatment.

The anticancer potential of juglone, a naphthoquinone derived from walnut trees, has been extensively studied; however, its hydrophobicity and toxicity obstruct its therapeutic applications. This study aimed to overcome these challenges by encapsulating juglone into poly (lactic-co-glycolic acid) (PLGA) nanoparticles and evaluating their antiproliferative and apoptotic effects on HeLa cells. Juglone nanoparticles (JNP) were obtained by single emulsion solvent evaporation method. Its key physicochemical properties, such as particle size, zeta potential, drug loading, release yield, and encapsulation efficiency values were calculated as 207.45 ± 1.67 nm, -24.12 ± 2.21 mV, 47.80, 66.90 and 90.12%, respectively. JNP's antiproliferative effects were compared to those of free juglone on HeLa cells. The calculated IC₅₀ values for free juglone and JNPs were 17.07 µM and 20.64 µM, respectively. Both formulations exhibited comparable dose-dependent antiproliferative effects across the tested concentrations. However, the nanoparticle-based delivery system demonstrated enhanced apoptotic activity, as evidenced by increased caspase-3 activation and greater suppression of BCL-2 levels relative to free juglone. These findings were further corroborated by TUNEL and immunocytochemical analyses, which confirmed the superior apoptotic induction by the nanosystem. Collectively, the results highlight the potential advantages of PLGA-based nanoparticle systems for the delivery of juglone, thereby improving its water solubility-a key limiting factor for its use-while minimizing its toxicity. These findings offer a promising approach for its application as an effective anticancer agent via nanoparticle-based delivery.

This study investigated the relationship between ferroptosis related genes and the prognosis of gastric cancer patients. Gene expression and corresponding clinical data were obtained from the TCGA database. Differentially expressed genes in gastric cancer were identified using R software, and prognostic-related genes were screened using univariate Cox regression analysis. Prognostic genes related to ferroptosis were determined using a Venn diagram. A prognostic model was constructed using LASSO-Cox regression analysis. Additionally, the expression of DUSP1 in gastric cancer was validated through immunohistochemistry, Western blot, and qRT-PCR. The impact of DUSP1 on ferroptosis was analyzed by measuring iron and lipid content in gastric cancer cell lines. A total of 407 gastric cancer patients were included as the training cohort. Fifteen prognostic genes related to ferroptosis were identified, and an 11-gene prognostic model was constructed. Risk scores were calculated for each patient, revealing that the overall survival rate was higher in the low-risk group compared to the high-risk group. ROC curves, PCA plots, and Kaplan-Meier survival curves demonstrated the model's efficacy in predicting 5-year survival rates (AUC = 0.716). Increased DUSP1 expression, correlated with higher Fe2+ and lipid ROS levels, was observed in gastric cancer cells with increasing Erastin concentration. The prognostic model effectively predicts gastric cancer patient outcomes. DUSP1 is lowly expressed in gastric cancer tissues and is associated with malignancy and metastasis, playing a role in ferroptosis in gastric cancer cells.