Clinical characteristics of liver injury in SARS-CoV-2 Omicron variant- and Omicron subvariant-infected patients.

INTRODUCTION AND OBJECTIVES: Liver injury in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant- and Omicron subvariant-infected patients is unknown at present, and the aim of this study is to summarize liver injury in these patients. PATIENTS AND METHODS: In this study, 460 SARS-CoV-2-infected patients were enrolled. Five severe or critical patients were excluded, and 34 patients were also excluded because liver injury was not considered to be related to SARS-CoV-2 infection. Liver injury was compared between Omicron and non-Omicron variants- and between Omicron subvariant-infected patients; additionally, the clinical data related to liver injury were also analyzed. RESULTS: Among the 421 patients enrolled for analysis, liver injury was detected in 76 (18.1%) patients, including 46 Omicron and 30 non-Omicron variant-infected patients. The ratios did not differ between Omicron and non-Omicron variant-, Omicron BA.1, BA.2 and BA.5 subvariant-infected patients (P>0.05). The majority of abnormal parameters of liver function tests were mildly elevated (1-3 × ULN), the most frequently elevated parameter of liver function test was γ-glutamyl transpeptidase (GGT, 9.5%, 40/421), and patients with cholangiocyte or biliary duct injury markers were higher than with hepatocellular injury markers. Multivariate analysis showed that age (>40 years old, OR=1.898, 95% CI=1.058-3.402, P=0.032), sex (male gender, OR=2.031, 95% CI=1.211-3.408, P=0.007), serum amyloid A (SAA) level (>10 mg/ml, OR=3.595, 95% CI=1.840-7.026, P<0.001) and vaccination status (No, OR=2.131, 95% CI=1.089-4.173, P=0.027) were independent factors related to liver injury. CONCLUSIONS: Liver injury does not differ between Omicron and non-Omicron variants or between Omicron subvariant-infected patients. The elevations of cholangiocyte or biliary duct injury biomarkers are dominant in SARS-CoV-2-infected patients.

Effect of atrial fibrillation on outcomes in patients with anterior circulation occlusion stroke receiving endovascular therapy.

Objective: Atrial fibrillation is one of the major risk factors of ischemic stroke. Endovascular thrombectomy (EVT) has become the standard treatment for acute ischemic stroke with large vessel occlusion. However, data regarding the impact of AF on the outcome of patients with acute ischemic stroke treated with mechanical thrombectomy are controversial. The aim of our study was to determine whether atrial fibrillation modifies the functional outcome of patients with anterior circulation acute ischemic stroke receiving EVT. Methods: We reviewed 273 eligible patients receiving EVT from January 2019 to January 2022 from 3 comprehensive Chinese stroke centers, of whom 221 patients were recruited. Demographics, clinical, radiological and treatment characteristics, safety outcomes, and functional outcomes were collected. Modified Rankin scale (mRS) score ≤ 2 at 90 days was defined as a good functional outcome. Results: In our cohort, 79 patients (35.74%) were eventually found to have AF. Patients with AF were elder (70.08 ± 11.72 vs. 61.82 ± 13.48 years, p = 0.000) and less likely to be males (54.43 vs. 73.94%, p = 0.03). The significant reperfusion rate (modified thrombolysis in cerebral infarction 2b-3) was 73.42 and 83.80% in patients with and without AF, respectively (p = 0.064). The good functional outcome (90-day modified Rankin scale: 0 to 2) rate was 39.24 and 44.37% in patients with and without AF, respectively (p = 0.460) after adjusting multiple confounding factors. There was no difference in the presence of symptomatic intracerebral hemorrhage between the two groups (10.13 vs. 12.68%, p = 0.573). Conclusion: Despite their older age, AF patients achieved similar outcomes as non-AF patients with anterior circulation occlusion treated with endovascular therapy.

Clinical features and predictive factors related to liver injury in SARS-CoV-2 Delta and Omicron variant-infected patients.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta and Omicron variants have become the dominant variants worldwide, and studies focused on liver injury in these patients are limited. MATERIALS AND METHODS: In this study, 157 SARS-CoV-2-infected patients were enrolled, including 77 Delta variant-infected patients and 80 Omicron variant-infected patients. Liver injury data and clinical data were summarized and compared between patients infected with the two variants, additionally, patients with or without liver injury were also compared and multivariate analysis was performed to explore the predictive factors related to liver injury in SARS-CoV-2-infected patients. RESULTS: Liver injury was found in 18 (23.4%)/15 (18.8%) in Delta/Omicron variant-infected patients on admission, and 4 (5.2%)/1 (1.3%) in Delta/Omicron variant-infected patients during hospitalization, respectively. The ratios of liver injury did not differ between the two groups ( χ2 = 1.571; P = 0.210). Among these patients, 17 (77.3%) and 12 (75.0%) Delta and Omicron variant-infected patients were considered to be related to SARS-CoV-2 infection, the biomarkers of liver function were mildly elevated, dominated by the parameter of cholangiocyte injury: 76.5% (13/17) and 83.3% (10/12) in Delta and Omicron variant-infected patients, and most of these patients recovered to normal during follow-up. Multivariate analysis showed that male sex [odds ratio (OR), 4.476; 95% confidence interval (CI), 1.235-16.222; P = 0.023] and high levels of peak viral load in the nasopharynx (OR, 3.022; 95% CI, 1.338-6.827; P = 0.008) were independent factors related to liver injury. CONCLUSION: Cholangiocyte injury biomarkers are dominated in Delta and Omicron variant-infected patients, male sex and high levels of peak viral load in the nasopharynx are predictive factors related to liver injury in SARS-CoV-2-infected patients.

Ramelteon ameliorated 1-methyl-4-phenylpyridinium (MPP+)-induced neurotoxicity in neuronal cells in a mitochondrial-dependent pathway.

Parkinson's disease (PD) is a common neurodegenerative disease with global health and economic impact. 1-methyl-4-phenylpyridinium (MPP+)-induced mitochondrial dysfunction and oxidative stress are reported to participate in the pathological mechanism of PD. Ramelteon is a novel oral hypnotic agent that has recently been reported to display neuronal protective effects. However, it is unknown whether Ramelteon possesses a beneficial effect in PD. In this study, we aimed to examine the potential function of Ramelteon in MPP+-challenged neurons. We found that Ramelteon rescued the cell viability reduced by MPP+-stimulation. Further, oxidative stress in MPP+-challenged SH-SY5Y cells was mitigated by Ramelteon as verified by the upregulated levels of mitochondrial reactive oxygen species (ROS) and protein carboxyl, and the upregulation of NADPH oxidase 4 (NOX-4). Furthermore, the declined mitochondrial membrane potential (ΔΨm) caused by MPP+ was reversed by Ramelteon. Importantly, Ramelteon attenuated MPP+-induced apoptosis, accompanied by a decreased ratio of Bax/Bcl-2, inhibition of cytochrome C release, and downregulation of cleaved caspase-3. For the first time, we conclude that Ramelteon might ameliorate MPP+-induced neurotoxicity in neuronal cells in a mitochondrial-dependent pathway.

Anagliptin Protected against Hypoxia/Reperfusion-Induced Brain Vascular Endothelial Permeability by Increasing ZO-1.

BACKGROUND AND PURPOSE: Cerebral ischemia-reperfusion injury is commonly induced during the treatment of ischemic stroke and is reported to be related to the blood-brain barrier destruction and brain vascular endothelial cell dysfunction. Anagliptin is a novel antidiabetic agent recently reported to protect neurons from oxidative stress. In the present study, we aim to investigate the protective property of anagliptin against oxygen-glucose deprivation and reperfusion (OGD/R)-induced injury on endothelial cells and clarify the potential underlying mechanism. METHODS: OGD/R modeling was established on bEnd.3 brain endothelial cells. Cell viability was detected using the MTT assay, and the mitochondrial reactive oxygen species (ROS) level was measured using the mitoses red staining assay. The endothelial monolayer permeability was determined using an FITC-dextran permeation assay. The expression levels of NOX-4 and ZO-1 were evaluated using qRT-PCR and Western blot assays. The expressions of MLC-2, p-MLC-2, and myosin light chain kinase (MLCK) were determined using Western blot. RESULTS: First, the decreased cell viability, upregulated NOX-4, and elevated mitochondrial ROS level in the endothelial cells induced by OGD/R were reversed by treatment with anagliptin. Second, the enlarged endothelial permeability and the decreased expression level of ZO-1 in the endothelial cells induced by OGD/R were alleviated by anagliptin. Third, the downregulation of ZO-1 and enlarged brain endothelial monolayer permeability induced by OGD/R were ameliorated by an MLCK inhibitor, ML-7. Lastly, the elevated expressions of MLCK and p-MLC-2 induced by OGD/R were suppressed by anagliptin. CONCLUSION: Anagliptin protected against hypoxia/reperfusion-induced brain vascular endothelial permeability by increasing the expression ZO-1, mediated by inhibition of the MLCK/MLC-2 signaling pathway.