Open Life Sciences最新文献

Retinal diseases, which can lead to significant vision loss, are complex conditions involving various cellular and molecular mechanisms. The interleukin-6 (IL-6) family, particularly Oncostatin M (OSM), has garnered attention for their roles in retinal inflammation, angiogenesis, and neuroprotection. This comprehensive review explores the dual nature of OSM and other IL-6 family members in retinal pathophysiology, highlighting their contribution to both degenerative and regenerative processes. The review also examines current research on OSM's interaction with key signaling pathways and discusses the potential of OSM and the IL-6 family as potential therapeutic targets. Understanding these mechanisms could lead to innovative treatments that modulate OSM activity, offering new avenues for managing retinal diseases and contributing to the development of more effective interventions.

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death and disability worldwide, and circRNA dysregulation is functionally associated with COPD. This study explored the potential of circRMRP and circRPL27 as biomarkers of COPD. Blood samples from COPD patients and healthy controls were collected. COPD patients were divided into mild, moderate, and severe groups according to lung function. Quantitative real-time polymerase chain reaction technology was used to determine the expression of circRPL27 and circRMRP in COPD. Receiver operating characteristic curve was drawn to explore the value of circRMRP and circRPL27 in diagnosing COPD. circRMRP and circRPL27 levels were elevated in serum of COPD patients and increased with the severity of COPD. CircRMRP and circRPL27 were associated with smoking history, WBC, and FEV1/FVC, and were positively correlated with smoking history and WBC, and negatively correlated with FEV1/FVC. In COPD, both circRMRP and circRPL27 had diagnostic values, but circRPL27 was better. circRMRP and circRPL27 may be useful non-invasive biomarkers for COPD diagnosis.

We investigated the protective effect of the NF-κB inhibitor, pyrrolidine dithiocarbamate (PDTC) on cardiomyocyte injury induced by HCN1 channel overexpression, and explored the underlying mechanisms. An HCN1 overexpression vector was constructed and transfected into H9C2 cells, followed by PDTC treatment. The experiments comprised the following groups: control, control + PDTC, overexpression negative control, HCN1 overexpression (HCN1-OE), and combined HCN1-OE + PDTC groups. Cell proliferation was assessed using the CCK8 assay, while apoptosis and reactive oxygen species (ROS) levels were measured by flow cytometry. ELISA kits were used to determine the levels of malondialdehyde, superoxide dismutase, and interleukin-1 beta. The HCN1-OE group exhibited increased apoptosis, elevated ROS, and decreased survival. Western blot (WB) analysis revealed increased levels of p65, p-IκB, IKKβ, NLRP3, Beclin-1, and LC3 II/I proteins in the HCN1-OE group. PDTC treatment for 48 h post-HCN1-OE resulted in improved cell viability, reduced apoptosis, and decreased ROS in the HCN1-OE + PDTC group. Immunofluorescence and WB analysis indicated a reduction in HCN1 and NF-κB pathway protein levels in the HCN1-OE + PDTC group. In conclusion, PDTC provided protection against HCN1-induced cardiomyocyte injury, potentially by modulating inflammatory cytokines and regulating the IKKβ/IκB/NF-κB signaling pathway.

This study sought to explore the value of major ozonated autohemotherapy (MOA) as a treatment for spinal cord injury (SCI) in a rat model system. In total, 54 female Sprague-Dawley rats were randomized into sham-operated, SCI model, and MOA treatment groups. We found that relative to the SCI model group, rats that underwent MOA treatment exhibited improved locomotor scores on days 14, 21, and 28 after injury (p < 0.05) together with reduced residual urine on days 5, 7, 14, and 21 after injury (p < 0.05). MOA treatment also lowered proinflammatory TNF-α, IL-1α, and C1q levels on day 3 post-injury (p < 0.05), decreased malondialdehyde levels, and enhanced superoxide dismutase activity (p < 0.001). Activated astrocytes in MOA-treated rats exhibited larger soma and higher levels of extracellular matrix secretion, whereas reactive microglia in the MOA group presented with a ramified morphology in contrast to the amoeboid morphology exhibited by these cells in SCI model rats. MOA offers potential value as a means of protecting spinal cord integrity, potentially through anti-inflammatory, antioxidant, and regulatory effects that shape the polarization of astrocytes and microglia.

Otitis media (OM) is a prevalent childhood ear disease characterized by inflammation of the middle ear cavity, which can lead to ear pain, fever, and hearing loss. The pathogenesis of OM is multifaceted, encompassing a variety of factors including bacterial or viral infections, host immune responses, and the function of middle ear epithelial cells. Boswellic acid (BA), a natural triterpene compound extracted from frankincense resin, has been proven to possess significant anti-inflammatory and immunomodulatory effects. This study aims to investigate the effects of BA on lipopolysaccharide (LPS)-stimulated inflammatory responses and apoptosis in human middle ear epithelial cells (HMEECs) and its potential mechanisms. Our findings demonstrated that BA enhances the proliferation of LPS-stimulated HMEECs and concurrently inhibits their apoptosis. In addition, BA blocked LPS-stimulated HMEEC inflammation. Mechanistically, BA suppressed the NF-κB/IκBα axis in LPS-stimulated HMEECs. In conclusion, BA effectively inhibits LPS-stimulated inflammation and apoptosis by mediating the NF-κB/IκBα axis, highlighting its potential as a therapeutic agent for OM.

Moroccan Cannabis sativa L. seeds were investigated for their phenolic profile and antidiabetic potential. Ultra-high-performance liquid chromatography with diode array detection and electrospray ionization mass spectrometry analysis revealed a rich phenolic composition, including benzoic acid, cannabisin B, genistein, and epicatechin. In vitro, the seed extract exhibited potent α-amylase inhibitory activity (half-maximal inhibitory concentration = 25.02 ± 4.03 μg/mL). In vivo studies in diabetic rats demonstrated significant hypoglycemic, hypolipidemic, hepatoprotective, and nephroprotective effects. Molecular docking studies further supported these findings, revealing strong interactions between identified phenolic and the α-amylase enzyme. These results highlight the potential of C. sativa seeds as a natural source of bioactive compounds for diabetes management.

Breast cancer (BC) has a prevalence rate of 21.8% among Saudi women and ranks as the third leading cause of death in Western nations. Nanotechnology offers innovative methods for targeted BC therapy, and this study explores the use of single-walled carbon nanotubes (SWCNTs) for delivering the senna leaf extract. The study evaluated the effects of increasing dosages of senna leaf extract conjugated to SWCNTs on MCF-7 cells. Cell viability was assessed using the MTT assay, while Giemsa staining revealed morphological changes. Additionally, the comet assay and agarose gel electrophoresis were employed to evaluate the pro-apoptotic potential. The potential of mitochondrial membrane and the production of reactive oxygen species (ROS) were investigated using the JC-1 dye. The results indicated that treated cells exhibited apoptotic characteristics, including elevated ROS levels and decreased mitochondrial membrane potential. In summary, the application of nanotechnology to deliver the senna leaf extract shows promise as a herbal treatment for BC, suggesting a potential breakthrough in combating this widespread and deadly disease.

Cell polarity is crucial in neurons, characterized by distinct axonal and dendritic structures. Neurons generally have one long axon and multiple shorter dendrites, marked by specific microtubule (MT)-associated proteins, e.g., MAP2 for dendrites and TAU for axons, while the scaffolding proteins AnkG and TRIM46 mark the axon-initial-segment. In tauopathies, such as Alzheimer's disease (AD), TAU sorting, and neuronal polarity are disrupted, leading to MT loss. However, modeling and studying MTs in human neuronal cells relevant to the study of AD and TAU-related neurodegenerative diseases (NDD) is challenging. To study MT dynamics in human neurons, we compared two cell culture systems: SH-SY5Y-derived neurons (SHN) and induced pluripotent stem cell-derived neurons (iN). Using immunostaining and EB3-tdTomato time-lapse imaging, we found AnkG absent in SHN but present in iN, while TRIM46 was present in both. TAU and MAP2 showed axonal and dendritic enrichment, respectively, similar to mouse primary neurons. Both neuron types exhibited polarized MT structures, with unidirectional MTs in axons and bidirectional MTs in dendrites. Polymerization speeds were similar; however, iNs had more retrograde MT growth events, while SHN showed a higher overall number of growth events. Thus, SHN and iN are both suitable for studying neuronal cell polarity, with SHN being particularly suitable if the focus is not the AIS.

In this study, we integrated transcriptomic and metabolomic analyses to achieve a comprehensive understanding of the underlying mechanisms of diabetic cardiomyopathy (DCM) in a diabetic rat model. Functional and molecular characterizations revealed significant cardiac injury, dysfunction, and ventricular remodeling in DCM. A thorough analysis of global changes in genes and metabolites showed that amino acid metabolism, especially the breakdown of branched-chain amino acids (BCAAs) such as valine, leucine, and isoleucine, is highly dysregulated. Furthermore, the study identified the transcription factor Gata3 as a predicted negative regulator of the gene encoding the key enzyme for BCAA degradation. These findings suggest that the disruption of BCAA degradation is a critical characteristic of diabetic myocardial damage and indicate a potential role for Gata3 in the dysregulation of BCAA metabolism in the context of DCM.

Gestational diabetes mellitus (GDM) is a common metabolic disorder during pregnancy characterized by glucose intolerance, which poses risks to both maternal and fetal health. Baicalein, a flavonoid derived from the roots of Scutellaria baicalensis Georgi, exhibits various biological functions and has been implicated in the modulation of several diseases. However, the regulatory effects and underlying mechanisms of Baicalein in GDM progression remain unclear. In this study, we found that Baicalein ameliorates metabolic disturbances in GDM mice by improving glucose tolerance, insulin sensitivity, fasting blood glucose levels, and plasma insulin levels. Additionally, Baicalein treatment positively impacted litter size and birth weight. GDM mice exhibited increased inflammation and oxidative stress, which were mitigated following Baicalein administration (40 mg/kg). Furthermore, elevated protein levels of NLRP3, IL-1β, and IL-18 observed in GDM mice were reduced by Baicalein treatment. In conclusion, Baicalein inhibits the NLRP3 inflammasome and alleviates placental inflammation and oxidative stress associated with GDM. These findings provide valuable insights into the potential therapeutic role of Baicalein in managing GDM.