Cell Biochemistry and Biophysics最新文献

The uncontrolled recurrence and metastasis of malignant tumors is an important reason for the high mortality of malignant tumors. Ras Suppressor Protein 1 (RSU1) has been proven to play an important role in the pathogenesis and progression of multiple malignant tumors, while its role in colorectal cancer (CRC) is rarely reported. The aim of this study is to investigate the expression and prognostic of RSU1 in CRC, and its effect on the proliferation and migration of the human colon adenocarcinoma cell lines, Caco-2 cells to reveal the potential mechanism of proliferation and migration of CRC. Firstly, Kaplan-Meier plotter, Tumor immune estimate resource version 2 (TIMER2.0) databases and so on were used to assess prognostic implications and correlation of immune infiltration of RSU1 expression in CRC. For further exploration, in vitro experiments were performed to knock down RSU1 expression in Caco-2 cells with RSU1-siRNA. CCK8 assay, colony formation assay and wound healing assay were executed to detect the proliferation and migration of Caco-2 cells after RSU1 knockdown. Finally, functional enrichment analyses of RSU1 in CRC were performed to explore the specific molecular mechanisms, and the expression of related molecules was further verified by western blot analysis. According to the bioinformatic databases, RSU1 expression was increased in CRC tissues compared with normal colorectal tissues. High RSU1 expression was not conducive to Overall (OS), Relapse-free survival (RFS) and Post-progression survival (PPS) prognosis. Moreover, high expression of RSU1 decreased the immune infiltration level of CD⁸⁺ T-cell in CRC, also account for that high RSU1 expression was may be related to the bad survival prognosis of CRC. Functionally, RSU1 knockdown inhibited proliferation and migration of Caco-2 cells. KEGG pathway enrichment analysis revealed a significant connection between RSU1 and the Phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway in CRC, western blot analysis also showed that RSU1 knockdown decreased PI3K and AKT protein expression. Silencing the RSU1 gene can significantly reduce the proliferation ability of Caco-2 cells and inhibit their migration behavior by suppressing the PI3K/AKT signaling pathway. Bioinformatics analysis indicated that RSU1 was highly expressed in CRC. Its high expression was not conducive to the prognosis of patients and would also reduce the immune infiltration level of CD⁸⁺ T cells. These findings provide a preliminary theoretical basis for the research on RSU1 as a potential target for prognosis assessment and immunotherapy of CRC.

Myocardial hypertrophy, a complex cardiovascular disorder, remains a significant challenge. NRG4 has shown protective effects against myocardial damage. Here, we clarified the role of NRG4 in angiotensin II (Ang II)-induced hypertrophy of AC16 cardiomyocytes. The Ang II-stimulated AC16 cell line was used as an in vitro model of myocardial hypertrophy. Immunofluorescence using an anti-α-actinin antibody was used to observe cell area and size. mRNA expression was detected by quantitative PCR, and protein levels were measured by immunoblot assay. ROS amount detection was performed by flow cytometry. The cell protein/DNA ratio and the levels of IL-1β, IL-18, MDA and SOD were tested using commercial kits. The relationship between PCBP2 and NRG4 mRNA was validated by luciferase, RNA immunoprecipitation (RIP), and mRNA stability assays. In Ang II-stimulated AC16 cells, PCBP2 and NRG4 were markedly downregulated. Increased NRG4 expression relieved Ang II-induced hypertrophy and fibrosis in AC16 cardiomyocytes. Moreover, NRG4 increase weakened NLRP3 inflammasome activation and oxidative stress in Ang II-stimulated AC16 cardiomyocytes. Mechanistically, PCBP2 stabilized NRG4 mRNA to increase NRG4 protein expression in Ang II-induced AC16 cardiomyocytes. NRG4 depletion counteracted the suppressive effects of PCBP2 upregulation on hypertrophy, NLRP3 inflammasome activation, and oxidative stress of Ang II-induced AC16 cardiomyocytes. Additionally, the PCBP2/NRG4 cascade regulated the AMPK/mTOR signaling pathway in Ang II-induced AC16 cardiomyocytes. Our data demonstrate that the previously uncharacterized PCBP2/NRG4 cascade attenuates Ang II-triggered hypertrophy, NLRP3 inflammasome activation, and oxidative stress of AC16 cardiomyocytes.

In this article, we have proposed a sensor capable of sensing and detecting various blood constituents within the terahertz frequency range. Our model has been constructed using COMSOL Multiphysics software, and we have analyzed the optical properties using the full vectorial finite-element method (FV-FEM). A solid core is chosen for the proposed sensor due to its unique ability to transmit light across a wide range of wavelengths. Since blood is a critical fluid in the human body, the identification of its components holds significant importance. Our innovative design features a spiral-shaped twin-core photonic crystal fiber (SSTC-PCF) sensor that targets key blood components having different refractive indices (RI), including water, plasma, white blood cells (WBCs), hemoglobin, and red blood cells (RBCs). The cladding in spiral geometry enhances the modal confinement and offers enhanced birefringence to our structure. In the proposed PCF design, different blood components are introduced into the small central elliptical hole serving as the sensing channel. Further, the sensing capabilities have been assessed by evaluating the coupling length and analyzing the transmission power spectrum, which has been calculated using the effective mode indices of the coupling modes. The presented model is simulated in the terahertz range (0.7-0.8 THz) to calculate optical properties. The proposed sensor is designed to work within a refractive index range of 1.33-1.40, allowing for effective detection of key blood components. The proposed SSTC-PCF sensor exhibits the highest sensitivity achieved at 5,75,511 nm/RIU with less coupling length and better than published previous works, which is the main feature of the proposed sensor. Additionally, maximum birefringence values for x-polarization are 3.27 × 10^-3, 3.67 × 10^-3, 3.90 × 10^-3, 4.44 × 10^-3 and 5.14 × 10^-3 for water, plasma, WBC, Hemoglobin, and RBC, respectively, and the highest coupling length values for x-polarization are 0.09 m for water, 0.08 m for plasma, 0.08 m for WBCs, 0.07 m for hemoglobin, and 0.06 m for RBC. This sensor design offers high sensitivity and a short coupling length, making it suitable for various applications in the biomedical field.

Wuzi Yanzong Pill (WZYZP) is a traditional Chinese medicine formula extensively used in China to treat male reproductive dysfunction, with a specific focus on invigorating the kidney. Despite its observed efficacy, the exact mechanisms and therapeutic targets remain unclear. The primary goal of this study is to elucidate the potential molecular targets and underlying mechanisms of WZYZP in the treatment of asthenozoospermia (AZS). It will be achieved through the integration of network pharmacology and bioinformatics analyses in a comprehensive and systematic approach. This study employed bioinformatics analysis and network pharmacology methodologies, encompassing: construction of protein-protein interaction (PPI) networks; development of 'Ingredients-Potential Target Genes-Signaling Pathways' (IPS) networks; Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis; differential gene analysis; molecular docking; and molecular dynamics simulations (MDS). Through network pharmacology analysis, we identified 485 potential targets of WZYZP. Cross-referencing with disease databases resulted in 57 intersecting targets pertinent to both WZYZP and AZS. Construction of the IPS network further determined eight core candidate targets: PIK3R1, MAPK3, GSK3B, AKT1, MAPK14, ESR1, ESR2, and CYP17A1. GO and KEGG pathway enrichment analyses highlighted significant involvement in prolactin signaling, endocrine resistance, and estrogen signaling pathways. Molecular docking and MDS confirmed stable binding of WZYZP components to all eight core targets. Our findings suggest that WZYZP may exert therapeutic effects in AZS by targeting eight pivotal genes (PIK3R1, MAPK3, GSK3B, AKT1, MAPK14, ESR1, ESR2, and CYP17A1). This is achieved through modulation of prolactin signaling, estrogen signaling, and endocrine resistance, thereby inhibiting inflammatory damage, antagonizing apoptotic signaling, maintaining hormonal homeostasis, and restoring metabolic imbalance.

Adenylate kinases (ADK) maintain cellular energy homeostasis and catalyse a reversible reaction that converts two molecules of ADP into ATP and AMP. ATP in Chlamydomonas reinhardtii flagella is utilised by dynein to generate flagellar beating. ATP must be constantly supplied and maintained; however, the constricted nature of flagella restricts the localisation of mitochondria in vicinity. We show that C. reinhardtii flagella carry conserved ADK domain-containing proteins that are large in number and longer than their cytosolic counterparts. Six of the eight flagellar ADKs are enriched in the central pair apparatus (CPA). Upon flagellar regeneration and resorption, the ADK activity changes, suggesting a shift in the energy demands for the two processes. The total ADK activity in regenerating flagella increased, and resorbing flagella showed an equal but reverse effect. ADKs help regenerate ATP locally and act as phosphotransfer agents that spatially direct the transfer of nucleotides. The ADP to ATP ratio during reflagellation and resorption suggests a role for ADKs in maintaining the nucleotide levels. To the best of our knowledge, this is the first study providing evidence for the role of ADK domain-containing proteins in maintaining ATP homeostasis in response to flagella regeneration and resorption.

The management of brain abscesses, particularly with Escherichia coli (E. coli) in immunocompromised patients, remains contentious. This study evaluates the bioactive potential of Ficus benghalensis extracts against brain abscess pathogens, including multidrug-resistant E. coli and Staphylococcus aureus (S. aureus), through phytochemical, pharmacological, and computational analyses. High yields (75-85%) were obtained from polar solvent extraction (acetone, methanol, ethyl acetate). Liquid chromatography-tandem mass spectrometry (LC-MS/MS) identified 30 bioactive compounds, including myricetin, naringenin-7-O-rutinoside, and harpagoside. Methanol extracts exhibited potent antimicrobial activity with inhibition zones of 18.2 mm (E. coli) and 17.9 mm (S. aureus) and minimum inhibitory concentration (MIC) values of 210-250 µg/mL. Ex vivo assays on clinical isolates showed dose-dependent inhibition (MIC50 = 150 µg/mL). Molecular docking indicated quercetin (-7.5 kcal/mol) and kaempferol (-7.8 kcal/mol) targeting E. coli FimH and OmpA, while lupeol (-9.1 kcal/mol) and ellagic acid (-8.7 kcal/mol) targeted S. aureus PBP2a and Hla. Pharmacokinetic analysis revealed quercetin and gallic acid as lead candidates with 100% gastrointestinal (GI) absorption and bioavailability (0.55-0.56), but limited blood-brain barrier (BBB) permeability (brain score: 0.24). Three-dimensional quantitative structure-activity relationship (3D-QSAR) comparative molecular field analysis (CoMFA) models (R² = 0.111, Q² = 0.00) emphasized steric and electrostatic interactions (84%) in bioactivity. These findings suggest that Ficus benghalensis holds potential as a multitarget antimicrobial agent for brain abscess therapy, with further optimization for central nervous system (CNS) delivery needed.

Royal jelly (RJ) is a natural product that reduces toxic effects and has anti-proliferative effects. The aim of the study is to increase the anticancer effect of Paclitaxel (PAX), which is used in cancer treatment, and to reduce its toxic effect with RJ in oral squamous carcinoma cells. Cytotoxicity tests of RJ and PAX substances were tested on healthy gingival HGF cells and their anti-proliferative effects on UPCI-SCC-131 cells with real-time cell analyzer (xCELLigence RTCA). Their anti-migratory properties were observed with wound healing assay. Glycolysis stress test was performed with Seahorse XFe24 to measure the glycolytic capacity. Total RNA-seq libraries were created and sequenced with NovaSeq 6000. Transcriptome profiles were created with bioinformatic analyses and functional enrichment analyses were performed. Results demonstrate that both RJ and PAX exhibit significant anti-proliferative effects against oral squamous cell carcinoma cells, as quantified by real-time cell analysis. Notably, RJ co-treatment mitigated PAX-induced cytotoxicity in healthy human gingival fibroblasts, suggesting a protective role against chemotherapy-associated toxicity. While both compounds inhibited cancer cell proliferation, PAX particularly displayed potent anti-migratory properties in wound healing assays, significantly impairing OSCC cell motility. Metabolic profiling revealed that the RJ-PAX combination therapy substantially reduced glycolytic capacity in OSCC cells, indicating disruption of their energy metabolism. Transcriptomic analysis identified downregulation of critical cell cycle regulators (MCM2, CDC25A, CCNE2) and DNA replication factors (RFC2, PCNA), along with modulation of MYC and E2F pathways, providing insights into the observed anti-cancer effects.