Omentin-1 May Be One Treatment Factor for Intravenous Thrombolysis of Acute Cerebral Infarction Through the Inhibition of NLRP3 Ubiquitination by AMPK Function: Preliminary Findings.

BACKGROUND: Acute cerebral infarction (ACI) is a common neurological disease that is associated with high morbidity, disability and mortality rates. At present, antiplatelet therapy is a necessary treatment for ACI. The present study aimed to investigate the effects of omentin-1 on the intravenous thrombolysis of ACI. OBJECTIVE: The present study aimed to investigate the effects of omentin-1 on the intravenous thrombolysis of ACI. MATERIAL AND METHODS: The mouse model of ACI was induced using male C57BL/6 mice through middle cerebral artery occlusion (MCAO). Meanwhile, the murine BV2 microglial cells were pretreated with 0.1 mg/ml of lipopolysaccharide (LPS), and then induced with 2 mM of adenosine triphosphate (ATP). RESULTS: The omentin-1 mRNA expression in patients receiving intravenous thrombolysis for ACI was down-regulated compared with the normal group. Additionally, the serum level of omentin-1 was negatively correlated with National Institute of Health Stroke Scale (NIHSS) score or serum level of IL-1ß or MMP-2 in patients receiving intravenous thrombolysis for ACI. Meanwhile, the serum mRNA expression of omentin-1 was positively correlated with Barthel index or high-sensitivity C-reactive protein (hs-CRP) in patients undergoing intravenous thrombolysis for ACI. As observed from the in vitro model, Omentin-1 reduced inflammation, promoted cell growth, alleviated ROS-induced oxidative stress, and enhanced AMPK activity through activating NLRP3 ubiquitination. Omentin-1 presented ACI in the mouse model of ACI. Regulating AMPK activity contributed to controlling the effects of Omentin-1 on the in vitro model. CONCLUSIONS: Omentin-1 reduced neuroinflammation and ROS-induced oxidative stress in the mouse model of ACI, which was achieved by inhibiting NLRP3 ubiquitination through regulating AMPK activity. Therefore, omentin-1 may serve as a treatment factor for the intravenous thrombolysis of ACI in further clinical application.

Spatial Multiomics Analysis in Psychiatric Disorders.

The aim of this study is to provide a comprehensive overview of spatial multiomics analysis, including its definition, processes, applications, significance and relevant research in psychiatric disorders. To achieve this, a literature search was conducted, focusing on three major spatial omics techniques and their application to three common psychiatric disorders: Alzheimer's disease (AD), schizophrenia, and autism spectrum disorders. Spatial genomics analysis has revealed specific genes associated with neuropsychiatric disorders in certain brain regions. Spatial transcriptomics analysis has identified genes related to AD in areas such as the hippocampus, olfactory bulb, and middle temporal gyrus. It has also provided insight into the response to AD in mouse models. Spatial proteogenomics has identified autism spectrum disorder (ASD)-risk genes in specific cell types, while schizophrenia risk loci have been linked to transcriptional signatures in the human hippocampus. In summary, spatial multiomics analysis offers a powerful approach to understand AD pathology and other psychiatric diseases, integrating multiple data modalities to identify risk genes for these disorders. It is valuable for studying psychiatric disorders with high or low cellular heterogeneity and provides new insights into the brain nucleome to predict disease progression and aid diagnosis and treatment.

Bortezomib induces cellular senescence in A549 lung cancer cells by stimulating telomere shortening.

Bortezomib (BTZ) is a first-generation proteasome inhibitor with anti-tumor properties for multiple myeloma and mantle cell lymphoma. Increasing evidence has shown that BTZ exhibits toxic effects on diverse tumor cells, including non-small cell lung cancer (NSCLC) cells. However, the mechanism has not been fully evaluated. Here, we examined the regulatory effect of BTZ on cellular senescence, a potent tumor suppressive mechanism, in NSCLC cell lines. SA-ß-gal staining assay showed that BTZ caused a significant increase in ß-Gal positive A549 cells. BTZ also induced cell cycle arrest on G0/G1 phase in A549 cells. Furthermore, telomerase activity was markedly reduced in A549 cells treated with BTZ. BTZ reduced the expression levels of hTERT, and the key proteins binding to telomeric DNA, including POT1 and TIN2. It also induced the expressions of the cell cycle-associated tumor suppressors p53 and p21 in A549 cells. Moreover, hTERT overexpression abolished the effects of BTZ on A549 cells. These results show that BTZ induced cellular senescence by stimulating telomere shortening. Our results provide experimental data for the potential clinical application of BTZ in NSCLC treatment.

Circ_0025039 acts an oncogenic role in the progression of non-small cell lung cancer through miR-636-dependent regulation of CORO1C.

Non-small cell lung cancer remains the leading cause of cancer-related death worldwide. Circular RNA plays vital roles in NSCLC progression. This study is designed to reveal the role of circ_0025039 in NSCLC cell malignancy. The RNA expression of circ_0025039, microRNA-636 (miR-636), and coronin 1C was detected by quantitative real-time polymerase chain reaction. Protein expression was checked by Western blot analysis or immunohistochemistry assay. Cell proliferation, migration, invasion, tube formation ability, sphere formation capacity, and apoptosis were investigated by cell counting kit-8, 5-Ethynyl-29-deoxyuridine, transwell assay, tube formation assay, sphere formation assay, and flow cytometry analysis, respectively. Mouse model assay was conducted to reveal the effect of circ_0025039 silencing on tumor formation in vivo. The interaction between miR-636 and circ_0025039 or CORO1C was identified through dual-luciferase reporter and RNA pull-down assays. The expression of circ_0025039 and CORO1C was significantly increased, while miR-636 was decreased in NSCLC tissues and cells compared with controls. Circ_0025039 depletion repressed NSCLC cell proliferation, migration, invasion, tube-forming capacity, and sphere formation ability, but induced cell apoptosis. The neoplasm formation was repressed after circ_0025039 silencing. Additionally, circ_0025039 acted as a sponge for miR-636, which was found to target CORO1C. Importantly, the contribution of circ_0025039 to NSCLC progression was mediated by miR-636/CORO1C axis. Circ_0025039 silencing repressed NSCLC malignant progression by reducing CORO1C expression through miR-636, showing the possibility of circ_0025039 as a therapeutic target for NSCLC.

Diagnosis and treatment for a case of Legionella longbeachae severe pneumonia and literature review. / 1ä¾‹é•¿æ»©å†›å›¢èŒæ€§é‡ç—‡è‚ºç‚Žè¯Šæ²»åˆ†æžåŠæ–‡çŒ®å¤ä¹ .

As a type of Legionella bacteria, Legionella longbeachae bacteria can lead to very rare legionella disease case in China with clinical characteristics, such as no typical early clinical symptoms, strong toxicity, high mortality, and not easy to detect by conventional etiology. A case of severe pneumonia caused by Legionella longbeachae infection was confirmed by bronchoalveolar lavage fluid pathogen metagenomics, and the patient's condition was improved after targeted anti-infection treatment. At present, our understanding in Legionella longbeachae severe pneumonia is limited. The diagnosis and treatment process of the patient with severe pneumonia of Legionella longbeachaeis retrospectively analyzed and the relevant literature was reviewed to provide the experience for its future diagnosis and treatment.

Syntenin overexpression in human lung cancer tissue and serum is associated with poor prognosis.

BACKGROUND: Lung cancer is the major malignant tumour. The present study was conducted to determine the expression level of syntenin in lung cancer tissues and serum from lung cancer patients and to explore its clinical significance. METHODS: Syntenin expression levels were determined in paraffin-embedded lung cancer tissue specimens (n = 191) using immunohistochemistry. The mRNA expressions of syntenin in fresh lung cancer tissues and the paracancerous tissues were examined by RT-qPCR (n = 25). Syntenin and VEGF expression levels were measured in serum from patients with lung cancer (n = 60) and control subjects (n = 30) using ELISA. The associations between syntenin and the clinicopathological features or prognosis in 191 patients with lung cancer were analysed. The correlation between the syntenin and VEGF levels in serum from 60 lung cancer patients was analysed. RESULTS: The expression levels of syntenin were significantly higher in lung cancer tissues than in paracancerous tissues based on immunohistochemistry and RT-qPCR, and elevated syntenin expression was significantly associated with tumour size (P = 0.002), TNM stage (P = 0.020), tumour distant metastasis (P = 0.033), overall survival (OS) (P = 0.002) and progression-free survival (PFS) (P = 0.001). Multivariate analysis revealed that increased expression of syntenin was an independent risk factor for OS (P = 0.006) and PFS (P < 0.001) in lung cancer patients. The expression levels of syntenin and VEGF in serum from lung cancer patients were higher than those from control subjects (P < 0.001, P < 0.001, respectively), and their expression levels were positively correlated (r = 0.49, P < 0.001). CONCLUSIONS: Syntenin expression is upregulated in lung cancer patients, and its serum expression level is positively correlated with VEGF. Moreover, syntenin overexpression was correlated with poor prognosis in patients with lung cancer.

Serum Aldosterone Is Associated with Cerebral Artery Atherosclerosis and Calcification.

BACKGROUND AND PURPOSE: Elevated serum aldosterone concentration is known to be linked with elevated risk of cerebrovascular events as a result of vascular senescence. We studied the association between serum aldosterone concentration and cerebral arteriosclerosis status involving cerebral atherosclerosis burden and cerebral vascular calcification. METHODS: A total of 207 patients (mean age = 62.40 ± 10.54, 70 female patients) admitted with acute ischemic stroke from a single center-based stroke registry were included in the study. The participants were categorized into 4 groups in accordance to the serum aldosterone concentration. Cerebral atherosclerosis burden was derived as the stenosis degree of main intracranial arteries, and cerebral artery calcification was investigated from the cavernous portions of both internal carotid arteries from brain computed tomography angiography. RESULTS: The median aldosterone was 146.00 pg/mL; interquartile range was 133.18-172.10 pg/mL. Advanced intracranial atherosclerosis was present in 134 patients (64.7%) and advanced intracranial arterial calcification was present in 77 patients (37.2%). The prevalence of cerebral atherosclerosis burden and cerebral artery calcification showed increasing tendency through the aldosterone quartiles. Multivariable logistic regression analysis including age, sex, vascular risk factors, estimated glomerular filtration rate and aldosterone quartiles disclosed that the highest serum aldosterone quartile was an independent predictor of advanced intracranial atherosclerosis (odds ratio, 5.07; 95% confidence interval, 1.82-14.17; Ptrend = .001) and advanced intracranial arterial calcification (odds ratio, 6.24; 95% confidence interval, 2.03-19.22; Ptrend = .001). CONCLUSIONS: An increased serum aldosterone concentration was independently associated with intracranial atherosclerosis burden and arterial calcification. Future studies should investigate whether aldosterone antagonists prevent stroke in at risk population.

Pentraxin-3 in Thrombolytic Therapy for Acute Ischemic Stroke: No Relation with Curative Effect and Prognosis.

BACKGROUND Pentraxin-3 (PTX3) is considered a high quality inflammatory marker of the severity and prognosis of several diseases, however, the value of PTX3 in thrombolytic therapy for acute ischemic stroke remains unclear and PTX3 is still controversial in evaluating the prognosis of stroke patients. In this study, we investigated the association of PTX3 with thrombolytic therapy in patients with acute ischemic stroke. MATERIAL AND METHODS Forty-seven stroke patients who received thrombolytic therapy within 4.5 hours after symptom onset were enrolled consecutively between July 2016 and June 2017. All the patients underwent multiphase CTA (computerized tomography angiography) or CT perfusion before thrombolysis with no indication for endovascular treatment. Initial and 24 hours of National Institute of Health Stroke Scale (NIHSS) scores and serum PTX3 level, stroke risk factors and predictors, and mRS (modified Rankin scale) at 3 months were collected prospectively. Predictors of thrombolytic therapy effect and long-term prognosis were investigated by univariate and multivariate logistic regression. RESULTS The 24 hour NIHSS score and the treatment time was associated with symptom improvement, while the PTX3 level had no association with neurological improvement and prognosis in stroke patients receiving thrombolytic therapy. CONCLUSIONS PTX3 is not suitable to serve as an indicator of thrombolytic efficacy and had no association with long-term prognosis in stroke patients receiving thrombolytic therapy.

Clinical Study of Intracranial and Extracranial Atherosclerotic Stenosis in Spontaneous Intracerebral Hemorrhage Patients.

BACKGROUND AND PURPOSE: Nowadays, researchers had begun to focus on the use of antiplatelet and statins in patients with spontaneous intracerebral hemorrhage (sICH), but atherosclerosis treatment remains uncertain in these patients. We aimed to investigate the incidence and characteristics of intracranial and extracranial atherosclerotic stenosis in these patients and analyze its related risk factors. METHODS: Intracranial and extracranial arteries of consecutive patients with sICH were studied retrospectively with computed tomography angiography of head and neck. The risk factors, severity, and distribution of atherosclerotic stenosis were examined and analyzed. RESULTS: We included 226 patients with sICH, of whom 110 patients (48.7%) had atherosclerotic stenosis. Of the patients, 57 (51.8%) had intracranial stenosis and 75 (68.2%) had multiple stenosis. A total of 1870 vessels were examined and 287 vessels (15.3%) had atherosclerotic stenosis, of which 217 cases (75.6%) were mild stenosis. Intracranial and extracranial atherosclerosis was more likely to be found in patients with advanced age (P < .001), diabetes mellitus (P = .008), non-deep hemorrhage (P = .011). CONCLUSIONS: Atherosclerotic stenosis is common in patients with sICH, and is characterized by mild stenosis and the involvement of multiple sites. The stenosis of the vertebrobasilar system is relatively severe. Advanced age, diabetes mellitus, and non-deep bleeding are its related risks.

Traditional Chinese Acupuncture for Poststroke Depression: A Single-Blind Double-Simulated Randomized Controlled Trial.

OBJECTIVE: To evaluate the effectiveness and possible side-effect of treating poststroke depression patients by traditional Chinese body acupuncture. DESIGN: Single-blind double-simulated randomized controlled trial. SETTING: Inpatient wards of neurology and rehabilitation departments. PARTICIPANTS: Sixty-eight (68) participants who met the criteria were randomly assigned into two groups, 34 cases (32 completed) into intervention group and 34 cases (33 completed) into control group. INTERVENTIONS: Body acupuncture (Shuigou GV 26, Neiguan PC 6, and Zusanli ST 36) and oral placebo were used in intervention group while fluoxetine and minimal nontraditional acupuncture (minimally active penetrating) were used in control group. Patients in both groups were treated separately once a day for 6 weeks. OUTCOME MEASURES: Outcomes were measured using the 17-item Hamilton Depression Rating Scale (HAMD-17), and side-effects were measured using the Side Effect Rating Scale (SERS) of Asberg and a self-designed needling adverse events scale. Clinical effects of both groups were statistically valued before treatment, week-2, week-6, and month-3. RESULTS: The total curative effects of both groups are similar (p > 0.05; evaluated in week-6 and month-3), while intervention group had an earlier onset time at week-2 (p < 0.05). The intervention group has fewer side-effects in week-2 (p < 0.05). CONCLUSIONS: Body acupuncture was effective in reducing stroke patients' depressive symptoms and had fewer side-effects. It should be considered as an option for neuropsychiatric sequelae of stroke.