Macrophage infiltration and polarization have been increasingly observed in intervertebral disc (IVD) degeneration (IDD). However, their biological roles in IDD are still unrevealed. We harvested ...conditioned media (CM) derived from a spectrum of macrophages induced from THP-1 cells, and examined how they affect nucleus pulposus cells (NPCs)
in vitro
, by studying cell proliferation, extracellular matrix (ECM) synthesis, and pro-inflammation expression; and
in vivo
by injection CM in a rat IDD model. Then, high-throughput sequencing was used to detect differentially expressed genes (DEGs). Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interaction (PPI) networks were used to further analysis. Higher CCR7+ (M1 marker) and CD206+ (M2 marker) cell counts were found in the degenerated human IVD tissues as compared with the control. Furthermore, the cell co-culture model showed M1CM attenuated NPC proliferation, downregulated the expression of ECM anabolic genes encoding aggrecan and collagen IIα1, upregulated the expression of ECM catabolic genes encoding MMP-13, and inflammation-related genes encoding IL-1β, IL-6, and IL-12, while M2CM showed contrasting trends. In IDD model, higher histological scores and lower disc height index were found following M1CM treatment, while M2CM exhibited opposite results. M1CM injection decreased ECM anabolic and increased ECM catabolic, as well as the upregulation of inflammation-related genes after 8 weeks treatment, while M2CM slowed down these trends. Finally, a total of 637 upregulated and 655 downregulated genes were detected in M1CM treated NPCs, and 975 upregulated genes and 930 downregulated genes in the M2CM groups. The top 30 GO terms were shown and the most significant KEGG pathway was cell cycle in both groups. Based on the PPI analysis, the five most significant hub genes were PLK1, KIF20A, RRM2, CDC20, and UBE2C in the M1CM groups and RRM2, CCNB1, CDC20, PLK1, and UBE2C in the M2CM groups. In conclusion, macrophage polarization exhibited diverse roles in IDD progression, with M1CM exacerbating cell proliferation suppression and IVD degeneration, while M2CM attenuated IDD development. These findings may facilitate the further elucidation of the role of macrophage polarization in IDD, and provide novel insights into the therapeutic potential of macrophages.
Patients with poor-grade aneurysm subarachnoid hemorrhage (SAH) have commonly been considered to have a poor prognosis. The objective of this study was to investigate the independent risk factors ...affecting clinical outcomes in intracranial aneurysm patients with poor-grade aneurysm subarachnoid hemorrhage (aSAH) underwent different intervention therapies.
A multicenter observational registry of 324 poor-grade aSAH patients treated at tertiary referral centers from October 2010 to March 2012 were enrolled in this study. The clinical data including patient characteristics on admission and during treatment course, treatment modality, aneurysm size and location, radiologic features, signs of cerebral herniation (dilated pupils), and functional neurologic outcome were collected. Clinical outcomes were assessed via a modified Rankin Scale at 12 months. Multivariate logistic regression models were used to develop prognostic models. The area under the receiver operator characteristic curves (AUC) and Hosmer-Lemeshow tests were used to assess discrimination and calibration. WAP score was developed to predict risk of poor outcome.
Older age, female gender, ventilated breathing status, non-reactive pupil response, pupil dilation, lower GCS score, a WFNS grade of V, intraventricular hemorrhage, a higher Fisher grade, a higher modified Fisher grade, and conservative treatment were calculated to be associated with a relatively poor outcome. Multivariate analyses revealed that older age, lower Glasgow coma scale score (GCS), the absence of pupillary reactivity, higher modified Fisher grade, and conservative treatment were independent predictors of poor outcome, showed good discrimination and calibration. Patients with WFNS grade V, older age and non-reactive pupillary reactivity were predicted to have a poor outcome by WAP risk score.
A simple WAP risk score had good discrimination and calibration in the prediction of outcome. The risk score can be easily measured and may complement treatment decision-making.
For catalytic materials, the characteristics of one-dimension and hollowness are the promotion factors for their full presentation of catalytic activity, and through a template-assisted method, both ...above superiorities can be fused simultaneously. Here, we proposed a novel strategy inspired by Pearson’s principle with Cu
2
O wires as templates, and prepared FeOOH hollow tubes, which covered by FeOOH scales. When applied as oxygen evolution reaction (OER) catalyst, the FeOOH scaly hollow tubes (FeOOH SHTs) showed outstanding catalytic activity with a low overpotential of 245 mV to drive a current density of 10 mA·cm
−2
, excellent kinetics manifesting as a low Tafel slope of 46.9 mV·dec
−1
, and robust stability. This work provides a new synthesis strategy for an ideal OER catalyst, FeOOH, with high inherent activity and enhances the feasibility to broaden the design ideas of transition metal-based catalysts.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Sensitization of central pain and inflammatory pathways play essential roles in migraine, a primary neurobiological headache disorder. Since hypoxia-inducible factor-1α (HIF-1α) is implicated in ...neuroprotection and inflammation inhibition, herein we investigated the role of HIF-1α in migraine. A chronic migraine model was established in mice by repeated injection of nitroglycerin (10 mg/kg, i.p.) every other day for 5 total injections. In the prevention and acute experiments, roxadustat, a HIF-1α stabilizer, was orally administered starting before or after nitroglycerin injection, respectively. Pressure application measurement, and tail flick and light-aversive behaviour tests were performed to determine the pressure pain threshold, thermal nociceptive sensitivity and migraine-related light sensitivity. At the end of experiments, mouse serum samples and brain tissues were collected for analyses. We showed that roxadustat administration significantly attenuated nitroglycerin-induced basal hypersensitivity and acute hyperalgesia by improving central sensitization. Roxadustat administration also decreased inflammatory cytokine levels in serum and trigeminal nucleus caudalis (TNC) through NF-κB pathway. Consistent with the in vivo results showing that roxadustat inhibited microglia activation, roxadustat (2, 10, and 20 μM) dose-dependently reduced ROS generation and inflammation in LPS-stimulated BV-2 cells, a mouse microglia cell line, by inhibiting HIF-1α/NF-κB pathway. Taken together, this study demonstrates that roxadustat administration ameliorates migraine-like behaviours and inhibits central pain sensitization in nitroglycerin-injected mice, which is mainly mediated by HIF-1α/NF-κB/inflammation pathway, suggesting the potential of HIF-1α activators as therapeutics for migraine.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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•Flavone 1,3,4-oxadiazole derivatives act as anti-inflammatory and anti-oxidant agents for treating Parkinson's disease.•The optimal compound F12 is obtained through SAR ...optimization.•Compound F12 significantly reduces oxidative stress and inflammation via Nrf2/ NF-κB signaling pathway.•Compound F12 improves MPTP-induced Parkinson's disease in vivo.
Parkinson's disease (PD) is a progressive neurodegenerative disorder with a complex etiology. Neuroinflammation and oxidative stress are important factors driving the progression of PD. It has been reported that 1,3,4-oxadiazole and flavone derivatives have numerous biological functions, especially in the aspect of anti-inflammatory and antioxidant. Based on the strategy of pharmacodynamic combination, we introduced 1,3,4-oxadiazole moiety into the flavonoid backbone, designed and synthesized a series of novel flavonoid 1,3,4-oxadiazole derivatives. Further, we evaluated their toxicity, anti-inflammatory and antioxidant activities using BV2 microglia. Following a comprehensive analysis, compound F12 showed the best pharmacological activity. In vivo, we induced the classical PD animal model by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) into C57/BL6J mice. Our results showed that compound F12 ameliorated MPTP-induced dysfunction in mice. Further, compound F12 reduced oxidative stress by promoting the nucleation of nuclear factor erythroid 2-related factor 2 (Nrf2) and decreased the inflammatory response by inhibiting the nuclear translocation of nuclear factor-κB (NF-κB) in vivo and in vitro. Meanwhile, compound F12 inhibited the mitochondrial apoptotic pathway to rescue microglia inflammation-mediated loss of dopaminergic neurons. In conclusion, compound F12 reduced oxidative stress and inflammation and could be as a potential agent for PD treatment.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Objective:
The aim of the study was to analyze the characteristics of renal function in patients diagnosed with COVID-19.
Methods:
In this retrospective, single-center study, we included all ...confirmed cases of COVID-19 in a tertiary hospital in Guangdong, China from January 20, 2020 to March 20, 2020. Blood and urine laboratory findings related to renal function were summarized, and the estimated glomerular filtration rate (eGFR) and endogenous creatinine clearance (Ccr) were also calculated to assess the renal function.
Results:
A total of 12 admitted hospital patients were diagnosed with COVID-19, included 3 severe cases, and 9 common cases. Serum creatinine (Scr) was not abnormally elevated in all of the patients, and blood urea nitrogen (BUN) was abnormally elevated in only 25.0% of the patients. However, compared with the recovery period, the patient's Scr and BUN increased significantly in peak of disease (p-scr = 0.002 & p-bun < 0.001). By observing the fluctuations in Scr and BUN from admission to recovery, it was found that the peak of Scr and BUN appeared within the first 14 day of the course of the disease. Urinary microprotein detection indicated that the abnormally elevated rates of urine microalbumin (UMA), α1-microglobulin (A1M), urine immunoglobulin-G (IGU), and urine transferring (TRU) standardized by urinary creatinine in peak of disease were 41.7, 41.7, 50.0, and 16.7%, respectively. The abnormal rates of the calculated eGFR and Ccr were 66.7 and 41.7%.
Conclusion:
Scr and BUN were generally increased during the course of COVID-19. Detection of urinary microproteins and application of multiple indicators assessment could be helpful for discovering abnormal renal function in patients with COVID-19. However, the evidence is limited due to the small sample size and observational nature. Additional studies, especially large prospective cohort studies, are required to confirm these findings.
Objective. To compare the current treatment approach in elderly patients with poor-grade aneurysmal subarachnoid hemorrhage (SAH) and identify the independent predictors of the outcome after ...aggressive surgical treatment. Method. This prospective, multicenter cohort study included 104 poor-grade aneurysmal SAH elderly patients, 60 years or older, treated in our institution from October 2010 to March 2013. Patients were grouped according to three treatment arms. Neurological outcome was assessed using the Glasgow Outcome Scale (GOS) at baseline and at a 12-month follow-up. Univariate and multivariate analysis were performed using the following factors: sex, age, smoking history, breathing ability, alcohol consumption, cerebral hernia, aneurysm location, aneurysm diameter, WFNS grade, CT Fisher grade, treatment approach, and the timing of the aneurysm surgery. Results. At the 12-month follow-up, patients in the coiling group and clipping group had better prognosis than patients in the palliative treatment group. Univariate analysis confirmed that the treatment approach, WFNS grade, CT Fisher grade, and age are critical factors for neurological outcomes in poor-grade SAH. Multivariate analysis indicated that WFNS grade V, CT Fisher grades 3–5, and palliative treatment were independent predictors of poor prognoses. Conclusion. Aggressive surgical treatment improves the prognoses in poor-grade aneurysm elderly patients with SAH. Elderly Patients of WFNS grade IV and CT Fisher grades 1-2 are more likely to have a better outcome.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
The aim of the present study was to evaluate the expression levels of caveolin-1 in the basilar artery following delayed cerebral vasospasm (DCVS) in a rat model of subarachnoid hemorrhage (SAH), in ...order to investigate the association between caveolin-1 and DCVS, and its potential as a treatment for DCVS of SAH. A total of 150 Sprague Dawley rats were randomly allocated into blank, saline and SAH groups. The SAH and saline groups were subdivided into days 3, 5, 7 and 14 following the establishment of the model. The murine model of SAH was established by double injection of autologous arterial blood into the cisterna magana and DCVS was detected using Bederson neurological severity scores. Hematoxylin and eosin (HE) staining was used to observe the inner perimeter of the basilar artery pipe and variations in the thickness of the basilar artery wall. Alterations in the levels of caveolin-1 protein in the basilar artery were measured using immunofluorescence and western blot analysis; whereas alterations in the mRNA expression levels of caveolin-1 were detected by reverse transcription-quantitative polymerase chain reaction. In the present study, 15 mice succumbed to SAH-induced DCVS in the day 3 (n=3), 5 (n=5) and 7 (n=2) groups. No mortality was observed in the blank control and saline groups during the process of observation in the SAH group, All mice in the SAH groups exhibited Bederson neurological severity scores ≥1; whereas no neurological impairment was detected in the blank and normal saline groups, demonstrating the success of the model. HE staining was used to assess vasospasm and the results demonstrated that the inner perimeter of the basal artery pipe decreased at day 3 in the SAH group; whereas values peaked in the day 7 group. The thickness of the basal artery wall significantly increased (P<0.05), as compared with the blank and saline groups, in which no significant alterations in the wall thickness and the inner perimeter of the basal artery pipe were detected. As detected by immunofluorescence and western blot analysis, the expression levels of caveolin-1 protein significantly decreased in the day 7 of SAH group, as compared with the blank and saline groups (P<0.01), in which no significant alterations were detected. Caveolin-1 mRNA expression levels significantly increased at the day 7 in the SAH group, as compared with the blank and the saline groups (P<0.01), as detected by RT-qPCR. Furthermore, significant differences were detected at day 14 in the SAH group, as compared with the blank and the saline groups (P>0.05), in which no significant alterations were detected. Therefore, the results of the present study demonstrated that caveolin-1 protein was downregulated in the basilar artery of a rat modeling SAH, which may be associated with DCVS. This suggested that caveolin-1 may be a potential target for the treatment of DCVS.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
We presented a case of successful awake endotracheal intubation in a patient with a giant goiter and severe tracheal stenosis. The patient had difficulty in airway management during the perioperative ...anesthesia due to tracheal deviation and stenosis caused by tumor compression. We applied a visual laryngeal mask combined with fiberoptic bronchoscope to visualize the whole procedure of endotracheal intubation, from visually assessing the glottic, subglottic, and the tracheal conditions, to evaluating the pressure of the tumor on the trachea and the maximum tracheal tube diameter that could be passed. During the entire process, the patient remained awake, maintained spontaneous breathing, and actively cooperated with the clinical staff. Hence, we demonstrated that this method is safe, effective, operable, and could be generalized as a form of endotracheal intubation for patients with known difficult airways.
This report delves into the diagnostic and therapeutic journey undertaken by a patient with high-dose cantharidin poisoning and multiorgan dysfunction syndrome (MODS). Particular emphasis is placed ...on the comprehensive elucidation of the clinical manifestations of high-dose cantharidin poisoning, the intricate path to diagnosis, and the exploration of potential underlying mechanisms.
A patient taking 10 g of cantharidin powder orally subsequently developed MODS. The patient was treated with supportive care, fluid hydration and antibiotics, and hemoperfusion and hemofiltration therapy for 24 h and successfully recovered 8 d after hospital admission. Cantharidin poisoning can cause life-threatening MODS and is rare clinically. This case underscores the challenge in diagnosis and highlights the need for early clinical differentiation to facilitate accurate assessment and prompt intervention.
This article has reported and analyzed the clinical data, diagnosis, treatment, and prognosis of a case of high-dose cantharidin poisoning resulting in MODS and reviewed the relevant literature to improve the clinical understanding of this rare condition.
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