Cell Biochemistry and Biophysics最新文献

Traumatic brain injury (TBI) is a common traumatic event that imposes a significant burden on families and society. Lipocalin (LCN) is a class of multifunctional secreted lipoprotein molecules. This study aimed to explore the role and possible mechanism of LCN2 in TBI. A rat model of TBI was constructed and adeno-associated virus-coated shRNA-LCN2 was used to silence LCN2 expression. The modified neurological severity score (mNSS), learning and memory ability, pathological injury of brain tissue, number of neurons, and expression of neurotrophic factors were analyzed, and the expression of inflammatory factors, M1/M2 polarization of microglia, and p38MAPK-PGC-1α-PPARγ pathway after LCN2 silencing were further detected. Results found that LCN2 was highly expressed in the brain tissue of TBI rats, and there were obvious learning and cognitive impairments and pathological injury of brain tissue. After silencing LCN2, the mNSS was further increased, and the learning and cognitive ability was weakened. Similarly, silencing LCN2 increased the brain tissue water content, aggravated the histopathology degree, decreased the number of surviving neurons, and reduced the expression of neurotrophic factors in TBI model rats. In addition, the expression of M1 proinflammatory cytokines and polarization markers in microglia of TBI was increased, and the expression of M2 cytokines and markers was decreased after silencing LCN2. Silencing LCN2 also inhibited the activation of the p38MAPK-PGC-1α-PPARγ pathway. In conclusion, LCN2 was released by surviving neurons after TBI, and the increased LCN2 activated the p38MAPK-PGC-1α-PPARγ pathway, which promoted M2 polarization of microglia, and secreted neurotrophic factors, thereby alleviating secondary brain injury.

Periodontitis, a chronic inflammatory condition, often results in gum tissue damage and can lead to tooth loss. This study explores the role of methyltransferase-like 3 (METTL3) in promoting osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) within an inflammatory microenvironment. An inflammatory environment was simulated in hPDLSCs using lipopolysaccharide (LPS). Both adipogenic and osteogenic differentiation capacities of hPDLSCs were assessed. In LPS-treated hPDLSCs, METTL3 was overexpressed, and alkaline phosphatase (ALP) staining was performed alongside measurements of ALP activity, pro-inflammatory cytokines, METTL3, miR-141-3p, pri-miR-141, Zinc finger E-box binding homeobox 1 (ZEB1), runt-related transcription factor 2 (RUNX2), osteocalcin (OCN). N6-methyladenosine (m6A) and pri-miR-141 levels were quantified, and the binding of miR-141-3p to ZEB1 was analyzed. The results demonstrated that osteogenic differentiation in hPDLSCs was diminished under inflammatory conditions, coinciding with downregulated METTL3 expression. However, METTL3 overexpression enhanced osteogenic differentiation. METTL3 facilitated the conversion of pri-miR-141 into miR-141-3p via m6A modification, resulting in increased miR-141-3p levels, which in turn suppressed ZEB1 expression. Inhibition of miR-141-3p or overexpression of ZEB1 partially counteracted the positive effects of METTL3 on osteogenic differentiation. In conclusion, these findings suggest that METTL3-mediated m6A modification promotes osteogenic differentiation of hPDLSCs within an inflammatory microenvironment through the miR-141-3p/ZEB1 axis.

Oral submucous fibrosis (OSF) is a precancerous lesion of the oral cavity. Areca nut consumption can cause OSF through sustained activation of buccal mucosal fibroblasts (BMFs). This study explored the effect of curcumin on arecoline-induced BMF activation and its mechanism of action. BMFs were isolated and identified by immunofluorescence detection of fibroblast surface markers vimentin and S100A4. After transfection with FOSL1- or MAPK8-related vectors, BMFs were activated by arecoline and treated with curcumin. Scratch and transwell assays were performed to detect cell migration. ChIP and luciferase reporter assays were conducted to detect the binding of FOSL1 to the MAPK8 promoter. RT-qPCR was used to detect FOSL1 and MAPK8 mRNA expression. Western blotting was used to detect FOSL1, MAPK8, COL1A1, α-SMA, Smad2, and p-Smad2 proteins. Curcumin treatment inhibited arecoline-induced fibroblast migration, reduced the expression of myofibroblast markers COL1A1, α-SMA, and p-Smad2, and downregulated the expression of FOSL1 and MAPK8. FOSL1 or MAPK8 overexpression enhanced migration and increased COL1A1, α-SMA, and p-Smad2 expression in curcumin-treated cells. FOSL1 bound to the MAPK8 promoter and promoted MAPK8 expression. Simultaneous FOSL1 overexpression and MAPK8 knockdown, compared to FOSL1 overexpression, reduced cell migration and inhibited COL1A1, α-SMA, and p-Smad2 expression. In conclusion, curcumin targets FOSL1 to reduce MAPK8 expression, thereby suppressing arecoline-induced fibroblast activation.

Breast cancer is a disease that seriously endangers the health of women. However, it is difficult to treat due to the emergence of metastasis and drug resistance. Exploring the metastasis mechanism of breast cancer is helpful to aim for the appropriate target. The epithelial-mesenchymal transition (EMT) is an important mechanism of breast cancer metastasis. Sodium channel 1.5(Na_V1.5) and the GTPase Rac1 are factors related to the degree of malignancy of breast tumors. The expression of Na_V1.5 and the activation of Rac1 are both involved in EMT. In addition, Na_V1.5 can change the plasma membrane potential (Vm) by promoting the inflow of Na⁺ to depolarize the cell membrane, induce the activation of Rac1 and produce a cascade of reactions that lead to EMT in breast cancer cells; this sequence of events further induces the movement, migration and invasion of tumor cells and affects the prognosis of breast cancer patients. In this paper, the roles of Na_V1.5 and Rac1 in EMT-mediated breast cancer progression were reviewed.

Osteoarthritis (OA) is a joint disease closely related to aging and characterized by degeneration of articular cartilage. Robinin is a natural agent with various pharmacological properties. Recently, Robinin has been found to have the potential to improve the bone-related diseases. However, its effect on OA development remained unknown. Here, we discuss the specific role and underlying mechanisms of Robinin in interleukin-1beta (IL-1β)-treated chondrocytes and OA mouse model. Chondrocytes were isolated from the mouse to conduct in vitro assays. We evaluated cell viability and apoptosis using Cell Counting Kit-8 (CCK-8) assay and flow cytometry analysis, respectively. Western blotting assessed the levels of proteins related to apoptosis, extracellular matrix (ECM), and signaling pathways. Immunofluorescence staining was used to detect the expression of ECM and signaling markers. ELISA was conducted to assess the levels of inflammatory markers. The OA mice model was established using surgical destabilization of the medial meniscus (DMM), and then H&E staining and Safranin O staining were conducted to observe the histopathological changes in synovial tissues. TUNEL assay was used to detect cell apoptosis in vivo. Real-time RT-PCR was operated to measure mRNA level in vitro and in vivo. We discovered that Robinin reversed the IL-1β-induced decrease in chondrocyte viability. Robinin suppressed IL-1β-induced apoptosis of chondrocytes. The ECM destruction and inflammatory response induced by IL-1β were markedly reversed by Robinin incubation in the mouse chondrocytes. Besides, the upregulated cytokine mRNA levels in IL-1β-treated chondrocytes were reduced by Robinin treatment. The downregulation of COL2A1 level and upregulation of MMP13 and ADAMTS5 levels were counteracted by Robinin treatment. Robinin reduced the protein levels of Toll-like receptor 2 (TLR2) and Toll-like receptor 4 (TLR4) but enhanced the level of phosphorylated p65 (p-p65) in IL-1β-stimulated chondrocytes and OA mice. Robinin mitigated inflammation, cell apoptosis and cartilage destruction in synovial tissues from the OA mice. In conclusion, Robinin alleviated OA development in vitro and in vivo via TLR2/TLR4/NF-κB signaling pathway.

Thiazolidinedione-naphthalene analogues were synthesized and evaluated for antidiabetic activity as Pancreatic α-Amylase (PAA) and intestinal α-glucosidase (IAG) inhibitors. The activity of the compounds (14a-g,17a-k) is compared with acarbose as the standard drug and all the compounds shows good to moderate antidiabetic activity. In-vitro PAA and IAG inhibition assay is performed for the all compounds, the compounds 17e shows superior PAA and IAG inhibitory activity with respective to standard (IC₅₀ = 12.455 ± 0.04 μM and 9.145 ± 0. 01 μM). The molecular interaction with PAA and IAG protein was also studied with the help of molecular docking studies using AutoDock software. while SwissADME and Osiris property explorer tools computed in-silico drug likeliness and toxicity properties. The in-silico results confirmed the 17e molecule as a superior drug with high binding affinity and good drug likeness against PAA and IAG, confirming in-vitro results. We also studied antioxidant activity (AOA) of all synthesized compounds and results confined that the compound 14g and 17e has good antioxidant potential IC₅₀ = 8.04 ± 0.02 μM and 6.36 ± 0.03 μM respectively among all compounds. In conclusion, in-vitro, in-silico antidiabetic and antioxidant studies revealed 17e compound was found to be potential compound.

Neuroblastoma is a cancer that occurs due to abnormal development of the sympathetic nervous system. The dysregulation of miR-9 and miR-222 plays a crucial role in neuroblastoma development. These microRNAs have a significant relationship with PTEN, caspase-9, and MMP14, which can potentially form the basis for the specific diagnosis and treatment of this disease. In our study, two neuroblastoma cell lines were divided into three groups based on whether they had been treated with miR-9, anti-miR-9, miR-222, or both. We evaluated various parameters in these groups, including migration (through a wound healing assay), apoptosis (using flow cytometry), and gene expression (through qRT-PCR). Additionally, we measured the expression levels of MMP14, miR-9, and miR-222 in plasma and CSF samples from neuroblastoma patients using ELISA and qRT-PCR. We found that patients with neuroblastoma had higher levels of MMP14 and miR-222 mRNA expression but lower levels of miR-9 mRNA expression. Furthermore, after treating the cell lines with anti-miR-9 and anti-miR-222, we observed increased levels of MMP14 expression, as well as PTEN and caspase-9. Additionally, the treatment with anti-miR-222 and anti-miR-9 led to an increase in the frequency of apoptosis and migration of cancer cells. Our research shows that the dysregulation of miR-9, miR-222, and MMP14 could be key indicators in the pathogenesis of neuroblastoma. We also found that up-regulation of miR-9 was associated with decreased disease severity, whereas up-regulation of miR-222 and MMP14 was linked to increased disease severity.

Diffuse large B-cell lymphoma (DLBCL), known as the predominant type of aggressive B-cell lymphoma, is biologically and clinically heterogeneous. The prognosis of DLBCL is quite different among subtypes. Hypoxia is one of the key elements in tumor microenvironment, promoting tumor progression by means of various mechanisms, such as increased proliferation, altered metabolism, enhanced angiogenesis, and greater migratory capability, among others. The primary purpose of this research is to investigate the connection between hypoxia-featured genes (HFGs), prognosis in DLBCL, and their capacity association with the immune microenvironment. Various hypoxia-associated patterns for DLBCL patients from GEO and TCGA databases were identified by means of an unsupervised consensus clustering algorithm. CIBERSORT and IOBR package is used to identify different immune infiltration status. To develop a predictive model using hypoxia-related genes, we conducted univariate Cox regression, multivariate Cox regression, and LASSO regression assessment. Subsequently, we confirmed the predictive importance of these hypoxia-associated genes, highlighting hypoxia-associated characteristics, and explored the connection between the hypoxia model and the immune environment. Three hypoxia clusters were identified. We also observed that each pattern of hypoxia response was significantly related to different prognoses. It was found that the immune status among hypoxia clusters is different. After developing a prognostic risk model using 5 hypoxia-related genes, we discovered that the risk score is related to immune factors and how effective drugs are in treating DLBCL. In DLBCL patients, varying hypoxia patterns correlate with both prognostic outcomes and the immune microenvironment. Hypoxia-featured genes (HFGs) function as a standalone predictive element in these patients. It is also potentially a reliable indicator for predicting clinical responses to ICI therapy and traditional drugs.

Cancer is considered to be among the main causes of death worldwide. Treatment options for cancer are numerous. The type of cancer and its stage of progression determine which kind of treatment is needed. Nanomedicine is a new field for the treatment of various diseases. Pharmaceutical nanocarriers can be fabricated from various materials such as polymers, metals, or lipid-based surfactants. Carnosine-loaded niosomes have emerged as a promising approach in targeted cancer therapy, offering potential advantages over conventional treatments such as chemotherapy and radiation, by improving drug delivery specificity and reducing side effects. The study demonstrates that the encapsulation of carnosine in niosomes enhances its stability and bioavailability, leading to a significant increase in anticancer efficacy. These findings suggest that niosome technology can serve as an effective delivery system for carnosine, potentially transforming its use in cancer treatment and paving the way for future research in targeted therapies. Nanomaterials provide a good delivery system for this method of treatment. It's used in the treatment and diagnosis of diseases. Numerous investigations have been conducted on nanoscale vesicular systems, such as the most recent generations of vesicular nanocarriers, liposomes, and niosomes. Lipophilic and hydrophilic bioactive chemicals are transported via the niosomes in a vesicle. Since niosomes are composed of non-ionic surfactants mixed with cholesterol or other amphiphilic substances, they have a wide range of applications. The therapy of cancer with carnosine-loaded niosomes is one of these uses. The body synthesizes carnosine, a histidine-containing dipeptide, by enzymatically mixing L-histidine and β-alanine. With its antioxidant activities, Carnosine is considered a drug that can reduce and treat cancerous cells and many other therapeutic applications.