Cell Biochemistry and Biophysics最新文献

Synephrine, a protoalkaloid found in Citrus aurantium (CA) peels, exerts lipolytic, anti-inflammatory, and vasoconstrictive effects; however, its antioxidant activity remains unclear. In this study, electron spin resonance spectroscopy revealed that synephrine scavenged both hydroxyl and superoxide anion radicals. Several external stimuli, such as H₂O₂, X-rays, and ultraviolet (UV) radiation, cause stress-induced premature senescence (SIPS). As oxidative stress induces SIPS, we hypothesized that synephrine, an antioxidant, would suppress H₂O₂-induced premature senescence in WI-38 cells. Synephrine significantly decreased the reactive oxygen species levels induced by H₂O₂, thereby reducing lipid peroxidation, and oxidative DNA damage and preventing SIPS. Additionally, synephrine inhibited mitochondrial dysfunction in H₂O₂-treated WI-38 cells. The expression levels of p53, p21, and p16^-INK4A, which are involved in the induction of cell cycle arrest in SIPS, were significantly lower in synephrine-treated cells than in untreated cells. Our results indicate that synephrine inhibits H₂O₂-induced oxidative stress and mitochondrial dysfunction, suppressing premature senescence by inhibiting activation of the p53-p21 and p16^-INK4A-pRB pathways.

Histone acetylation is the process by which histone acetyltransferases (HATs) add an acetyl group to the N-terminal lysine residues of histones, resulting in a more open chromatin structure. Histone acetylation tends to increase gene expression more than methylation does. In the central nervous system (CNS), histone acetylation is essential for controlling the expression of genes linked to cognition and learning. Histone deacetylases (HDACs), "writing" enzymes (HATs), and "reading" enzymes with bromodomains that identify and localize to acetylated lysine residues are responsible for maintaining histone acetylation. By giving animals HDAC inhibitors (HDACis), it is possible to intentionally control the ratios of "writer" and "eraser" activity, which will change the acetylation of histones. In addition to making the chromatin more accessible, these histone acetylation alterations re-allocate the targeting of "readers," including the transcriptional co-activators, cAMP response element-binding protein (CBP), and bromodomain-containing protein 4 (Brd4) in the CNS. Conclusive evidence has shown that HDACs slow down the progression of Alzheimer's disease (AD) by reducing the amount of histone acetylation, decreasing the activity of genes linked to memory, supporting cognitive decline and Amyloid beta (Aβ) protein accumulation, influencing aberrant tau phosphorylation, and promoting the emergence of neurofibrillary tangles (NFTs). In this review, we have covered the therapeutic targets and functions of HDACs that might be useful in treating AD.

Salidroside, a natural herb, exerts considerable anti-tumor effects in various human cancers. Evidence unveils that Salidroside mediates gene expression to affect cancer progression. Our work intended to uncover the molecular mechanism of Salidroside functional role in keloid. Expression analysis for JAG1 and miR-26a-5p in tissues and cells was performed using qRT-PCR or western blotting. For functional analysis, cell proliferation, apoptosis and migration were ascertained by CCK-8, flow cytometry and Transwell assay, respectively. The putative binding relationship between JAG1 and miR-26a-5p was further confirmed by dual-luciferase reporter assay. Salidroside exerted pharmacological properties in keloid and impaired keloid fibroblast (KF) viability. JAG1 was upregulated in keloid tissues, and its expression was repressed by Salidroside in KFs. Salidroside depleted KF proliferation and migration but stimulated apoptosis, and JAG1 knockdown largely strengthened the functional effects of Salidroside. MiR-26a-5p interacted with JAG1 3'UTR and expressed with an opposite pattern with JAG1 in keloid. Inhibition of miR-26a-5p largely abolished the effects of JAG1 knockdown in Salidroside-treated KFs, leading to the recovery of KF aggressive behaviors. Salidroside blocked KF aggressive progression by upregulating miR-26a-5p to inhibit JAG1, which provided evidence on the anti-tumor effects of Salidroside in human keloid.

Intervertebral disc degeneration (IDD) is the main pathological factor resulting in low back pain (LBP), the leading cause of disability globally. Inflammatory response and extracellular matrix (ECM) degradation are critical pathological features in the development of IDD. Gastrodin (GAS), a phenol compound isolated from Gastrodia elata Blume, plays an anti-inflammatory role in experimental models of multiple human diseases. Our study aimed to elucidate whether GAS alleviates TNF-α-induced inflammation in nucleus pulposus (NP) cells and IDD in vivo. The cytotoxicity of GAS was assessed by CCK-8 assay. Rat primary NP cells were stimulated with TNF-α to induce inflammatory response. The expression of proinflammatory cytokines, catabolic genes, and anabolic genes was detected by RT-qPCR, western blotting, and immunofluorescence staining. NF-κB and MAPK pathway activation was determined through western blotting and immunofluorescence staining. The IDD rat model was established by using percutaneous needle puncture. The therapeutic effects of GAS were confirmed by histology analysis. We found that TNF-α stimulation enhanced proinflammatory cytokine (COX2, iNOS, IL-6, and IL-1β) expression in NP cells, which was reversed by GAS treatment. GAS offset TNF-α-induced upregulation in catabolic gene (MMP3, MMP9, and MMP13) expression and downregulation in anabolic gene (Collagen II, SOX9, and Aggrecan) expression. The loss of ECM in TNF-α-treated NP cells was mitigated by GAS treatment. Mechanically, GAS abolished TNF-α-induced increase in p-IKKα, p-IKKβ, p-IκBα, p-p65, p-ERK, p-p38, and p-JNK protein levels in NP cells. In puncture-induced IDD rat models, GAS administration improved intervertebral disc (IVD) structure, increased Collagen II expression, and reduced the levels of proinflammatory factors in IVDs. Overall, GAS alleviates the inflammation and ECM degradation in NP cells via inhibiting NF-κB and MAPK pathway activation and alleviates IDD in vivo, which may be a novel treatment strategy for IDD.

Total glucosides of paeony (TGP) have been investigated for their effects on cardiomyocyte hypertrophy induced by angiotensin II (Ang II). In this study, rat cardiomyocyte H9c2 cells were treated with various doses of TGP (0, 12.5, 25, 50, 100, 200, and 400 μmol/L), and cell viability was assessed using the MTT method to determine an optimal dose. To establish the cardiomyocyte hypertrophy model, Ang II (1 μmol/L) was used. The experimental groups included the control (Ctrl) group, the hypertrophy group (Ang II), the TGP treatment group (TGP+Ang II), and a combined treatment group (TGP+Ang II+LY), where LY294002, a PI3K/Akt inhibitor, was used. The surface area of H9c2 cells was analyzed using image analysis software, and apoptosis was assessed via flow cytometry. Western blotting was employed to evaluate markers related to cell proliferation, cardiac hypertrophy, apoptosis, and autophagy, as well as the phosphorylation of the PI3K/Akt pathway. The results revealed that Ang II inhibited cell viability and increased cell surface area, apoptosis, and autophagy, all of which were significantly reversed by TGP treatment. Moreover, the addition of LY294002 partially attenuated the effects of TGP, reducing cell viability and promoting hypertrophy, apoptosis, and autophagy. Additionally, Ang II reduced PI3K/Akt signaling activity, while TGP restored it. LY treatment reversed the effects of TGP and suppressed the PI3K/Akt pathway. In conclusion, TGP improves cardiomyocyte hypertrophy induced by Ang II by activating the PI3K/Akt signaling pathway.

Sensorineural hearing loss (SNHL) is an increasingly prevalent sensory disorder, but the underlying mechanisms remain poorly understood. Adaptor related protein complex 2 subunit beta 1 (AP2B1) has been indicated to be detectable in mature cochleae. Nonetheless, it is unclear whether AP2B1 is implicated in the progression of SNHL. Male CBA/J mice were exposed to 2-20 kHz broadband noise at 96 or 101 dB SPL to induce temporary or permanent threshold shifts (TTS or PTS). Auditory brainstem responses were measured for hearing loss evaluation. Bioinformatics analysis was used to predict the upstream miRNAs of Ap2b1. RT-qPCR and western blotting were utilized to determine miR-145b and AP2B1 expression in mouse cochleae. Luciferase reporter assay was implemented to verify the interaction between Ap2b1 and miR-145b. Bioinformatics analysis identified miR-145b as an upstream miRNA of Ap2b1. AP2B1 expression was decreased and miR-145b expression was increased in mouse cochleae after PTS noise exposure. miR-145b targeted and negatively regulated Ap2b1 in PTS noise-exposed mice. Depletion of miR-145b alleviated auditory threshold shifts and outer hair cell loss in mice with exposure to PTS noise. In conclusion, inhibition of miR-145b ameliorates noise-induced SNHL in mice by upregulating AP2B1 expression.

This study aims to explore the efficacy of neutrophil membrane nanovesicles (NMNVs) in the treatment of acute kidney injury caused by sepsis (S-AKI). Moreover, its effects on renal function indicators in plasma [creatinine (CREA), urea (UREA)], oxidative stress factor [malondialdehyde (MDA)], inflammatory factor [myeloperoxidase (MPO), histone H4 (H4), and macrophage inflammatory protein-2 (MIP-2)] are studied. Sixty SPF grade adult male Wistar rats in a healthy state under natural infection were randomly divided into blank, LSP, and experimental groups, with 20 rats in each group. After 7 days of adaptive feeding, a S-AKI model was established in the control group and the experimental group. The control group was treated with red blood cell membrane nanovesicles (RBC-NVs), the experimental group was treated with NMNVs, and the blank group was normal rats. The clinical treatment and changes in renal function indicators of the tested rats were observed and recorded. The total effective rate of treatment in the experimental group was higher than that in the controlling group (P < 0.05). Moreover, 1 h after the construction of the S-AKI model, the CREA, UREA, MDA, MPO, H4, MIP-2 in the controlling group and experimental group were higher than those in the blank group. At 7 and 14 h after constructing S-AKI model, the CREA, UREA, MDA, MPO, H4, and MIP-2 in the controlling and experimental groups decreased. However, the above indicators in the experimental group were lower than those in the controlling group (P < 0.05), and the comparison between this group and the blank group showed P > 0.05. In summary, the efficacy of NMNV in treating S-AKI is significant, as it can reduce CREA, UREA, MDA, MPO, as well as H4 and MIP-2, effectively controlling disease progression.

The nutritional status of fish is essential for its health, experimental studies, and aquaculture practices. The current study investigated the impact of food deprivation on biochemical parameters, histology of skin, gill, and kidney tissues, and ultrastructure of gills in Clarias batrachus. Fish were subjected to food deprivation for 2, 7, and 15 days resulting in (a) significant increase in plasma cortisol levels, (b) no significant changes in plasma osmolality and plasma glucose content, and (c) significant decrease in liver and muscle glycogen contents. A substantial damage was detected in skin, gill, and kidney tissues with histological alterations in a time-dependent manner. Skin tissue displayed melanomacrophage aggregation, excoriated epidermis and dermis. In gill tissue, epithelial lifting, edema, desquamation, deformed secondary lamellae, and lamellar hyperplasia were observed. Kidney tissue exhibited degenerated tubules, melanomacrophage aggregations, and shrunken renal tubule. Scanning electron microscopy revealed that food deprivation-induced marked presence of mucus, chloride cells, and pavement cells with well-defined microridges and microbridges following 2 days, opening of chloride cells was more prominent after 7 days, while more mucus secretion was observed after 15 days. After food deprivation, alterations in biochemical and histological parameters, and ultrastructural changes in target tissues reflect physiological and morphological disturbances in fish. The novelty of this study is that these parameters can be considered as biomarkers of feeding stress in fish and fish health and can provide important insights for better aquaculture practices.

Background: Endometriosis (EMS) is a difficult gynecological disease to cure. Frizzled-7 (FZD7) has been shown to be associated with the development of EMS, but its specific mechanism remains unclarified. This study aims to explore the role of FZD7 in EMS.

Methods: RT-qPCR and western blot were used to detect the expression level of FZD7 in human endometrial stromal cells (hESCs) and human ectopic endometrial stromal cell line hEM15A. The interfering plasmid of FZD7 was established. CCK-8, EdU, wound healing, transwell invasion, and cytoskeletal staining assays were applied to evaluate the role of FZD7 silencing in hEM15A cell proliferation, invasion, and migration. Tube forming ability of cells was evaluated by tube formation assay. Cellular VEGF, GSH, and MDA levels were measure by kits. Intracellular lipid ROS and Fe²⁺ levels were tested using C11-BODIPY (581/591) and FeRhoNox-1 probes, respectively. The ferroptosis-related protein SLC7A11, GPX4, and ACSL4 expressions were analyzed using western blot. The effects of ferroptosis on endometriotic cell viability, migration, and angiogenesis were further analyzed with the addition of an ferroptosis inhibitor (Fer-1).

Results: FZD7 was upregulated in hEM15A cells, and silencing of FZD7 inhibited cell proliferation, migration, invasion, and angiogenesis abilities. Downregulation of FZD7 decreased cellular GSH level and elevated MDA level. Knockdown of FZD7 also caused an increase in intracellular ROS and Fe²⁺ levels, as well as the downregulation of SLC7A11 and GPX4 levels and the upregulation of ACSL4 level, which are hallmarks of ferroptosis. However, the inhibitory effects of FZD7 knockdown on hEM15A cell progression were reversed when ferroptosis inhibitor Fer-1 added.

Conclusion: The above indices suggest that FZD7 knockdown regulates endometriotic cell proliferation, invasion, migration, and angiogenesis via ferroptosis.