Ferroptosis is a necrotic form of regulated cell death that was associated with lipid peroxidation and free iron‐mediated Fenton reactions. It has been reported that iron deficiency had been ...implicated in the pathogenesis of intervertebral disc degeneration (IVDD) by activating apoptosis. However, the role of ferroptosis in the process of IVDD has not been illuminated. Here, we demonstrate the involvement of ferroptosis in IVDD pathogenesis. Our in vitro models show the changes in protein levels of ferroptosis marker and enhanced lipid peroxidation level during oxidative stress. Safranin O staining, hematoxylin‐eosin staining, and immunohistochemical were used to assess the IVDD after 8 weeks of surgical procedure in vivo. Treatment with ferrostatin‐1, deferoxamine, and RSL3 demonstrate the role of ferroptosis in tert‐butyl hydroperoxide (TBHP)‐treated annulus fibrosus cells (AFCs) and nucleus pulposus cells (NPCs). Ferritinophagy, nuclear receptor coactivator 4 (NCOA4)‐mediated ferritin selective autophagy, is originated during the process of ferroptosis in response to TBHP treatment. Knockdown and overexpression NCOA4 further prove TBHP may induce ferroptosis of AFCs and NPCs in an autophagy‐dependent way. These findings support a role for oxidative stress‐induced ferroptosis in the pathogenesis of IVDD.
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Ferroptosis is a necrotic form of regulated cell death that was associated with lipid peroxidation and free iron‐mediated Fenton reactions. It has been reported that iron deficiency had been implicated in the pathogenesis of intervertebral disc degeneration (IVDD) by activating apoptosis. However, the role of ferroptosis in the process of IVDD has not been illuminated. Here, we demonstrate the involvement of ferroptosis in IVDD pathogenesis.
High dose and long‐term steroid treatment can alter antioxidative ability and decrease the viability and function of osteoblasts, leading to osteoporosis and osteonecrosis. Ferroptosis, a new type of ...cell death characterized by excessive lipid peroxidation due to the downregulation of GPX4 and system Xc−, is involved in glucocorticoid‐induced osteoporosis. Endothelial cell‐secreted exosomes (EC‐Exos) are important mediators of cell‐to‐cell communication and are involved in many physiological and pathological processes. However, the effect of EC‐Exos on osteoblasts exposed to glucocorticoids has not been reported. Here, we explored the role of EC‐Exos in glucocorticoid‐induced osteoporosis. In vivo and in vitro experiments indicated that EC‐Exos reversed the glucocorticoid‐induced osteogenic inhibition of osteoblasts by inhibiting ferritinophagy‐dependent ferroptosis.
Here, we explored the role of EC‐Exos in glucocorticoid‐induced osteoporosis. In vivo and in vitro experiments indicated that EC‐Exos reversed the glucocorticoid‐induced osteogenic inhibition of osteoblasts by inhibiting ferritinophagy‐dependent ferroptosis.
The literature on cases of acute disseminated encephalomyelitis (ADEM) associated with SARS-CoV-2 infection has been rapidly increasing. However, the specific clinical features of ADEM associated ...with SARS-CoV-2 (SARS-CoV-2-ADEM) have not been previously evaluated. We screened all articles resulting from a search of PubMed and Web of Science databases looking for reports of ADEM published between December 01, 2019, and June 5, 2021. Of the 48 ADEM cases identified from 37 studies, 34 (71%) had ADEM while 14 (29%) were of AHLE. RT-PCR for SARS-CoV-2 was positive in 83% (
n
= 19) of patients. 26 patients (54%) were male, and 18 patients (38%) were female, with a male to female sex ratio of 1.4:1; median age was 44 (1.4–71) years. 9 patients (19%, 9/48) were children. Of the 9 children patients, their median age was 9 years (range 1.4–13 years), 6 patients (67%) were female, and 2 patients (22%) were male, with a female to male sex ratio of 3:1.39 patients (81%) was performed CSF analysis. PCR for SARS-CoV-2 tested positive in 3 patients (14%, 3/22) on CSF sample. 31 (64%) of patients had a poor outcome on discharge from hospital. Five (10%) patients died in hospital. Compared to classic ADEM, SARS-CoV-2-ADEM have a more longer duration between the onset of the antecedent infective symptoms and the start of ADEM symptoms, the older age distribution of the patients, relatively poor outcome, a lower full recovery rate, a more frequently brain lesions involved the periventricular white matter and corpus callosum, and less frequently affected the deep gray matter. Taken together, the present comprehensive review reveals that although rare, ADEM can be associated with SARS-CoV-2 infection. SARS-CoV-2-ADEM seems to share most features of classic ADEM, with moderate discrepancies from the classical ADEM.
•The preferential adsorption of CO2 over CH4 improves with coal rank.•Pore structure of coal affects the thermodynamics of adsorption of CO2 and CH4.•Adsorbed CO2 has a more ordered configuration ...than CH4 on different rank coals.
In this paper, the pore structures of three different rank coals sampled from China (anthracite, bituminous coal and lignite) were characterized by CO2 and N2 adsorption. The isothermal adsorption curves of CO2 and CH4 on three samples were measured by gravimetric method and fitted by Langmuir model. The preferential selectivity (αCO2/CH4) was calculated using the Langmuir parameters of CO2 and CH4, and the Henry’s coefficient (KH) was obtained with the help of virial equation. More importantly, a comparative analysis of adsorption thermodynamics of CO2 and CH4 on three different rank coals, including surface potential (Ω), Gibbs free energy change (ΔG) and entropy loss (ΔS), was presented according to the adsorption data. It is found that the uptakes of CO2 and CH4 on anthracite are the largest, followed by lignite and bituminous coal in sequence. αCO2/CH4 increases with the increase of coal rank. Low temperature helps injected CO2 to displace pre-adsorbed CH4. The KH values on anthracite are the biggest, while KH values on bituminous coal are the smallest. Ω, ΔG and ΔS of CO2 and CH4 all exhibit a U-shaped function with maturity. Anthracite has the highest Ω, ΔG and ΔS, while bituminous coal has the lowest Ω, ΔG and ΔS. The thermodynamics parameters of Ω, ΔG and ΔS are affected by pore size distributions of three coals. Ω, ΔG and ΔS of CH4 are smaller than those of CO2. CO2 adsorption on coal is more favorable and spontaneous, and adsorbed CO2 molecules form a more efficient packing on coal.
The main pathological mechanism of intervertebral disc degeneration (IVDD) is the programmed apoptosis of nucleus pulposus (NP) cells. Oxidative stress is a significant cause of IVDD. Whether ...mitophagy is induced by strong oxidative stress in IVDD remains to be determined. This study aimed to investigate the relationship between oxidative stress and mitophagy and to better understand the mechanism of IVDD in vivo and in vitro. To this end, we obtained primary NP cells from the human NP and subsequently exposed them to TBHP. We observed that oxidative stress induced mitophagy to cause apoptosis in NP cells, and we suppressed mitophagy and found that NP cells were protected against apoptosis. Interestingly, TBHP resulted in mitophagy through the inhibition of the HIF-1α/NDUFA4L2 pathway. Therefore, the upregulation of mitochondrial NDUFA4L2 restricted mitophagy induced by oxidative stress. Furthermore, the expression levels of HIF-1α and NDUFA4L2 were decreased in human IVDD. In conclusion, these results demonstrated that the upregulation of NDUFA4L2 ameliorated the apoptosis of NP cells by repressing excessive mitophagy, which ultimately alleviated IVDD. These findings show for the first time that NDUFA4L2 and mitophagy may be potential therapeutic targets for IVDD.
Effective therapeutic targets for triple‐negative breast cancer (TNBC), a special type of breast cancer (BC) with rapid metastasis and poor prognosis, are lacking, especially for patients with ...chemotherapy resistance. Decitabine (DCA) is a Food and Drug Administration‐approved DNA methyltransferase inhibitor that has been proven effective for the treatment of tumors. However, its antitumor effect in cancer cells is limited by multidrug resistance. Cancer stem cells (CSCs), which are thought to act as seeds during tumor formation, regulate tumorigenesis, metastasis, and drug resistance through complex signaling. Our previous study found that miR‐155 is upregulated in BC, but whether and how miR‐155 regulates DCA resistance is unclear. In this study, we demonstrated that miR‐155 was upregulated in CD24−CD44+ BC stem cells (BCSCs). In addition, the overexpression of miR‐155 increased the number of CD24−CD44+ CSCs, DCA resistance and tumor clone formation in MDA‐231 and BT‐549 BC cells, and knockdown of miR‐155 inhibited DCA resistance and stemness in BCSCs in vitro. Moreover, miR‐155 induced stemness and DCA resistance by inhibiting the direct target gene tetraspanin‐5 (TSPAN5). We further confirmed that overexpression of TSPAN5 abrogated the effect of miR‐155 in promoting stemness and DCA resistance in BC cells. Our data show that miR‐155 increases stemness and DCA resistance in BC cells by targeting TSPAN5. These data provide a therapeutic strategy and mechanistic basis for future possible clinical applications targeting the miR‐155/TSPAN5 signaling axis in the treatment of TNBC.
To develop a machine learning model for predicting acute respiratory distress syndrome (ARDS) events through commonly available parameters, including baseline characteristics and clinical and ...laboratory parameters.
A secondary analysis of a multi-centre prospective observational cohort study from five hospitals in Beijing, China, was conducted from January 1, 2011, to August 31, 2014. A total of 296 patients at risk for developing ARDS admitted to medical intensive care units (ICUs) were included. We applied a random forest approach to identify the best set of predictors out of 42 variables measured on day 1 of admission.
All patients were randomly divided into training (80%) and testing (20%) sets. Additionally, these patients were followed daily and assessed according to the Berlin definition. The model obtained an average area under the receiver operating characteristic (ROC) curve (AUC) of 0.82 and yielded a predictive accuracy of 83%. For the first time, four new biomarkers were included in the model: decreased minimum haematocrit, glucose, and sodium and increased minimum white blood cell (WBC) count.
This newly established machine learning-based model shows good predictive ability in Chinese patients with ARDS. External validation studies are necessary to confirm the generalisability of our approach across populations and treatment practices.
BackgroundThe effectiveness of endovascular treatment (EVT) in patients with mild stroke (National Institutes of Health Stroke Scale score ≤5) and acute anterior circulation large vessel occlusion ...(AACLVO) remains unknown.ObjectiveTo conduct a meta-analysis to compare the efficacy and safety of EVT in patients with mild stroke and AACLVO.MethodsEMBASE, Cochrane Library, PubMed, and Clinicaltrials.gov databases were searched until October 2022. Both retrospective and prospective studies which compared the clinical outcomes between EVT and medical treatment were included. ORs and 95% confidence intervals (CIs) for excellent and favorable functional outcomes, symptomatic intracranial hemorrhage (ICH), and mortality were pooled using a random-effects model. A propensity score (PS)-based methods adjusted analysis was also performed.Results4335 patients from 14 studies were included. In patients with mild stroke and AACLVO, EVT presented no marked differences in excellent and favorable functional outcomes and mortality compared with medical treatment. A higher risk of symptomatic ICH (OR=2.79; 95% CI 1.49 to 5.24; P=0.001) was observed with EVT. Subgroup analysis revealed that EVT had potential benefit for proximal occlusions with excellent functional outcomes (OR=1.68; 95% CI 1.01 to 2.82; P=0.05). Similar results were observed when PS-based methods adjusted analysis was used.ConclusionEVT did not significantly benefit clinical functional outcomes in comparison with medical treatment in patients with mild stroke and AACLVO. However, it may improve functional outcomes when treating patients with proximal occlusion, despite being associated with an increased risk of symptomatic ICH. Stronger evidence from ongoing randomized controlled trials is required.
The widespread Early Cretaceous plutons intruding along the southern Great Xing'an Range (SGXR) provide evidence for tectonic evolution of the region. Petrological, geochemical, zircon U-Pb ...geochronology, and zircon Hf isotopic studies are conducted on intrusions from Bianjiadayuan and Hongling areas. These suites classify as A2-type granites and monzodiorites, respectively. The 138-133 Ma A2-type granites originated from partial melting of continental crustal materials at high temperatures and shallow depths with significant addition of juvenile mafic lower crust sourced from a metasomatized mantle. The 136-134 Ma monzodiorites originated from the partial melting of an enriched mantle that was modified by melts of a previously subducted slab coupled with crustal contamination. The Early Cretaceous magmatism in the SGXR occurred in two periods: ∼145-136 Ma (peak at ∼139 Ma; εHf (t) = 5 to 10) and ∼136-130 Ma (peak at ∼131 Ma; εHf (t) = -10 to 15). The Early Cretaceous granite-monzodiorite suite in the SGXR suggests a bimodal magmatism in an extensional setting. The ∼145-130 Ma magmatism may have been triggered by asthenospheric upwelling induced by the Mongol-Okhotsk oceanic slab breakoff and large-scale lithospheric delamination resulting from post-orogenic extension. The variation of subduction direction of the Paleo-Pacific Ocean likely triggered a change in stress regime at ca. 136 Ma and likely promoted the lithospheric delamination beneath the SGXR resulting in intense magmatism originating from various sources. As such, the Paleo-Pacific Oceanic subduction likely played an important role in the Early Cretaceous magmatism in the SGXR.
Objective
Lumbar disc degeneration (LDD) is a common cause of low back pain and disability, and its prevalence increases with age. The aim of this study is to investigate whether endplate Hounsfield ...unit (HU) values have an effect on lumbar disc degeneration (LDD) after transforaminal lumbar interbody fusion (TLIF) surgery in patients with degenerative lumbar stenosis.
Methods
This study was a retrospective analysis of patients who underwent TLIF surgery in January 2016 to October 2019. One hundred and fifty‐seven patients who underwent TLIF surgery for degenerative lumbar stenosis were enrolled in this study. Demographic data was recorded. VAS and ODI values were compared to assess the surgical outcomes in patients with or without process of LDD after TLIF surgery. Correlation analysis was performed to investigate associations between LDD and endplate HU value. Binary logistic regression analysis was carried out to study relationships between the DDD and the multiple risk factors.
Results
There was a statistically significant correlation between LDD, body mass index (BMI), age, paraspinal muscle atrophy, and total endplate scores (TEPS). Also, a strong and independent association between endplate HU value and LDD was found at every lumbar disc level (p < 0.01). After conditioning on matching factors, multivariate logistic regression analysis showed that higher endplate HU (odds ratio OR: 1.003, p = 0.003), higher TEPS (OR: 1.264, p = 0.002), higher BMI (odds ratio OR: 1.202, p = 0.002), a smaller cross‐sectional area (CSA) of the paraspinal muscle preoperatively (OR: 0.096, p < 0.001) were significant predictors of LDD development after TLIF surgery.
Conclusions
There is a significant association between LDD and endplate HU value after TLIF surgery in patients with degenerative lumbar stenosis. Beyond that, results from this study provide a mechanism by which high endplate HU value predisposes to LDD after TLIF surgery.
Measurement of the Hounsfield units (HU) values of endplate. Locating the endplate in the sagittal plane then trailing edge of hyperintense area and recording the mean HU value in the coronal plane.
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