This study aimed to explore the role of mesenchymal stromal cells (MSCs)-derived exosomes (MSCs-Exo) in the cerebral ischemia-reperfusion (I/R) injury.
Exosomes were isolated from MSCs of adult ...C57BL/6J mice by the gradient centrifugation method. The expression of miR-26a-5p and CDK6 in MSCs-Exo and mice brain tissues were evaluated by qRT-PCR and western blot. miR-26a-5p mimics and miR-NC were transfected into MSCs, and exosomes were isolated from the MSCs stably expressing miR-26a-5p. Then MSCs-Exo-miR-26a-5p mimics or MSCs-Exo-miR-NC was injected into mice through the tail vein, or added into medium to stimulate BV-2 cells. Cell viability was evaluated by CCK-8 assay. Cell apoptosis was detected by flow cytometry. The apoptosis in brain tissues was evaluated by TUNEL staining assay. Bioinformatics analysis and luciferase reporter assay were performed to determine the binding relationship between miR-26a-5p and CDK6.
miR-26a-5p was downregulated and CDK6 was upregulated in MSCs-Exo of MCAO-mice and OGD-induced MSCs. MSCs-Exo-miR-26a-5p mimics significantly reduced cell apoptosis of OGD-injured BV-2 cells. MSCs-Exo-miR-26a-5p mimics significantly reduced the infarct volume of MCAO-induced mice. Luciferase reporter assay revealed that CDK-6 was a target of miR-26a-5p. In addition, MSCs-Exo-miR-26a-5p mimics significantly decreased the expression of CDK6 in both OGD-induced BV-2 cells and the brain tissues of MCAO-treated mice.
Our results indicated that MSCs‑Exo attenuated I/R injury in mice by inhibiting microglia apoptosis might via exosomal miR-26a-5p mediated suppression of CDK6. Our study shed light on the application of MSC-Exo as a potential therapeutic tool for cerebral I/R injury.
Any abnormal activation of primordial follicles and subsequent depletion can irreversibly diminish the ovarian reserve, which is one of the major chemotherapy-induced adverse effects in young ...patients with cancer. Herein, we investigated the effects of rapamycin on the activation and development of ovarian follicles to evaluate its fertility-sparing therapeutic value in a cyclophosphamide (CTX)-treated mouse model. Based on ovarian histomorphological changes and follicle counting in 50 SPF female C57BL/6 mice, daily administration of 5 mg/kg rapamycin for 30 days was deemed an ideal dosage and duration for administration in subsequent experiments. Compared with the control group, rapamycin treatment inhibited the activation of quiescent primordial follicles, with no obvious side effects observed. Finally, 48 mice were randomly divided into four groups: control, rapamycin-treated, cyclophosphamide-treated, and rapamycin intervention. Body weight, ovarian histomorphological changes, number of primordial follicles, DDX4/MVH expression, apoptosis of follicular cells, and expression of apoptosis protease-activating factor (APAF)-1, cleaved caspase 3, and caspase 3 were monitored. Co-administration of rapamycin reduced primordial follicle loss and the development of follicular cell apoptosis, thereby rescuing the ovarian reserve after CTX treatment. On analyzing the mTOR signaling pathway, we observed that rapamycin significantly decreased CTX-mediated overactivation of mTOR and its downstream molecules. These findings suggest that rapamycin exhibits potential as an ovarian-protective agent that could maintain the ovarian primordial follicle pool and preserve fertility in young female patients with cancer undergoing chemotherapy.
Methylation modifications play pertinent roles in regulating gene expression and various biological processes. The silencing of the demethylase enzyme TET1 can affect the expressions of key oncogenes ...or tumour suppressor genes, thus contributing to tumour formation. Nonetheless, how TET1 affects the progression of cervical cancer is yet to be elucidated. In this study, we found that the expression of TET1 was significantly downregulated in cervical cancer tissues. Functionally, TET1 knockdown in cervical cancer cells can promote cell proliferation, migration, invasion, cervical xenograft tumour formation and EMT. On the contrary, its overexpression can reverse the aforementioned processes. Moreover, the autophagy level of cervical cancer cells can be enhanced after TET1 knockdown. Mechanistically, methylated DNA immunoprecipitation (MeDIP)-sequencing and MeDIP quantitative real-time PCR revealed that TET1 mediates the methylation of autophagy promoter regions. These findings suggest that TET1 affects the autophagy of cervical cancer cells by altering the methylation levels of NKRF or HIST1H2AK, but the specific mechanism needs to be investigated further.
Pre-eclampsia (PE), associated with placental malperfusion, is the primary reason for maternal and perinatal mortality and morbidity that can cause vascular endothelial injury and multi-organ injury. ...Despite considerable research efforts, no pharmaceutical has been shown to stop disease progression. If women precisely diagnosed with PE can achieve treatment at early gestation, the maternal and fetal outcomes can be maximally optimized by expectant management. Current diagnostic approaches applying maternal characteristics or biophysical markers, including blood test, urine analysis and biophysical profile, possess limitations in the precise diagnosis of PE. Biochemical factor research associated with PE development has generated ambitious diagnostic targets based on PE pathogenesis and dissecting molecular phenotypes. This review focuses on current developments in biochemical prediction of PE and the corresponding interventions to ameliorate disease progression, aiming to provide references for clinical diagnoses and treatments.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Disordered coagulation contributes to death in sepsis and lacks effective treatments. Existing markers of disseminated intravascular coagulation (DIC) reflect its sequelae rather than its causes, ...delaying diagnosis and treatment. Here we show that disruption of the endothelial Tie2 axis is a sentinel event in septic DIC. Proteomics in septic DIC patients revealed a network involving inflammation and coagulation with the Tie2 antagonist, angiopoietin-2 (Angpt-2), occupying a central node. Angpt-2 was strongly associated with traditional DIC markers including platelet counts, yet more accurately predicted mortality in 2 large independent cohorts (combined N = 1,077). In endotoxemic mice, reduced Tie2 signaling preceded signs of overt DIC. During this early phase, intravital imaging of microvascular injury revealed excessive fibrin accumulation, a pattern remarkably mimicked by Tie2 deficiency even without inflammation. Conversely, Tie2 activation normalized prothrombotic responses by inhibiting endothelial tissue factor and phosphatidylserine exposure. Critically, Tie2 activation had no adverse effects on bleeding. These results mechanistically implicate Tie2 signaling as a central regulator of microvascular thrombus formation in septic DIC and indicate that circulating markers of the Tie2 axis could facilitate earlier diagnosis. Finally, interventions targeting Tie2 may normalize coagulation in inflammatory states while averting the bleeding risks of current DIC therapies.
•Photo-active species generated from three metal oxide–silica nanocomposites suspension were investigated.•The amount of active species (OH, O2−, 1O2 and e−) varied with different ...nanocomposites.•CuO–SiO2 exhibited most obviously photocatalytic activity toward degradation of bisphenol A, and followed by Fe2O3–SiO2 and ZnO–SiO2.
Metal oxide nanocomposites with photocatalytic activity have the potential for many applications in environmental remediation and biomedicine. In this study, we investigated the formation and stabilization of electrons/holes from three metal oxide–silica nanocomposites (CuO–SiO2, Fe2O3–SiO2 and ZnO–SiO2) under irradiation by electron paramagnetic resonance (EPR) technology. The characteristic EPR signals with g=2.00070–2.00105, ΔHp-p=2.17–2.37G were determined, which corresponded to lattice-trapped electrons. Moreover, the generation of active species from CuO–SiO2, Fe2O3–SiO2 and ZnO–SiO2 in aqueous solution under irradiation was also systematically studied. The results showed that all the three nanocomposites could generate hydroxyl radical, singlet oxygen and electron. CuO–SiO2 was more effective than Fe2O3–SiO2 and ZnO–SiO2 in producing hydroxyl radical and electrons, while ZnO–SiO2 was the most efficient in generating singlet oxygen. In addition, CuO–SiO2 exhibited most obviously photocatalytic activity toward degradation of bisphenol A, followed by Fe2O3–SiO2 and ZnO–SiO2. These findings will provide vital insights into photocatalytic mechanisms and potentially photoinduced toxicity of metal oxide–silica nanocomposites.
In this study, a facile synthesis of fluorescence carbon dots (CDs) from sweet potato was performed through hydrothermal treatment. The obtained CDs with quantum yield of 8.64% have good ...dispersibility due to the soluble functional groups on their surfaces. The characterization of CDs was carried out and their possible formation mechanism was also discussed. In addition, the cytotoxicity results showed that the CDs exhibit non toxicity within 100μg/mL. At this concentration, the CDs were applied in cell imaging, indicating that they are promising fluorescent probes for biological imaging. In addition, the fluorescence of CDs was quenched by Fe3+ with a linear concentration of 1 to 100μM, associated with the limit of detection of 0.32μM. Subsequently, the CDs were successfully applied for Fe3+ probing in living cells.
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•The carbon dots (CDs) were prepared from biomass by eco-friendly treatment.•The formation of CDs is mostly like that of fullerene.•The CDs exhibit multicolor for cell imaging.•The CDs are applied for Fe3+ in living cells.
Bi-based nanomaterials, such as Bi
2
Se
3
, play an important part in biomedicine, such as photothermal therapy (PTT) and computed tomography (CT) imaging. Polyethylenimine (PEI)-modified ultrasmall ...Bi
2
Se
3
nanodots were prepared using an ultrafast synthetic method at room temperature (25°C). Bi
2
Se
3
nanodots exhibited superior CT imaging performance, and could be used as effective photothermal reagents owing to their broad absorption in the ultraviolet–visible–near infrared region. Under irradiation at 808 nm, PEI-Bi
2
Se
3
nanodots exhibited excellent photothermal-conversion efficiency of up to 41.3%. Good biocompatibility and significant tumor-ablation capabilities were demonstrated
in vitro
and
in vivo
. These results revealed that PEI-Bi
2
Se
3
nanodots are safe and a good nanotheranostic platform for CT imaging-guided PTT of cancer.
This study aimed to analyze the clinical features of myasthenia gravis (MG) in combination with the afterdischarges and compare the characteristics of afterdischarges in MG with different serum ...antibodies.
Ninety-two patients with MG were analyzed retrospectively. The afterdischarges were investigated using motor nerve conduction examination, F-wave examination, and repetitive nerve stimulation (RNS).
Afterdischarges were observed after the M wave in 14 of 92 patients. Three of these 14 patients tested positive for the muscle-specific tyrosine kinase antibody (MuSK-Ab), and 11 patients tested positive for the acetylcholine receptor antibody (AchR-Ab). The characteristics of the afterdischarges on RNS differed distinctly between the two antibody groups. The afterdischarges occurred on the first stimulation, but decreased on the second and subsequent stimulations in patients with MuSK-MG, while the afterdischarges continued to occur on each stimulation in patients with AchR-MG.
The characteristics of the afterdischarges on RNS enabled easy identification of their synaptic or neurogenic nature.
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