A systematic review and meta-analysis were conducted to evaluate the diagnostic accuracy of substantia nigra hyper-echogenicity by transcranial sonography (TCS) for the diagnosis of Parkinson's disease (PD). PubMed, Embase and the Cochrane Library were electronically searched from inception to June 2018 for all relevant studies. The methodological quality of each study was evaluated by two independent reviewers, who used the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Articles reporting information sufficient to calculate the sensitivity and specificity of TCS to diagnose PD were included. Statistical analysis included data pooling, heterogeneity testing, sensitivity analyses and forest meta-regression. Thirty-nine studies (3123 participants with PD) were analyzed. The pooled sensitivity and specificity of TCS were 0.84 (95% confidence interval: 0.81-0.87) and 0.85 (0.80-0.88), respectively, for differentiating PD from normal controls or participants with other parkinsonian syndromes. In the secondary outcome, PD participants exhibited a significant increase in substantia nigra areas than either normal controls (0.14 [0.12-0.16], p < 0.0001) or participants with other parkinsonian syndromes (0.11 [0.08-0.13], p < 0.0001). This meta-analysis revealed the high diagnostic performance of TCS in differentiating patients with PD from both normal controls and participants with other parkinsonian syndromes.

Lentinan (LNT), a type of polysaccharide derived from Lentinus edodes, has manifested protective effects during liver injury and hepatocellular carcinoma, but little is known about its effects on nonalcoholic fatty liver disease (NAFLD). This study aimed to investigate whether LNT can affect the progression of NAFLD and the associated mechanisms. C57BL/6J mice were fed a normal chow diet or a high-fat diet (HFD) with or without LNT (6 mg/kg/d). AML12 cells were exposed to 200 μM palmitate acid (PA) with or without LNT (5 μg/mL). After 21 wk of the high-fat diet, LNT significantly decreased plasma triglyceride levels and liver lipid accumulation, reduced excessive reactive oxygen species production, and subsequently attenuated hepatic apoptosis in NAFLD mice. These effects were associated with increased PPARα levels, a decreased Bax/Bcl-2 ratio, and enhancement of the antioxidant defense system in vivo. Similar effects were also observed in cultured cells. More importantly, these protective effects of LNT on palmitate acid-treated AML12 cells were almost abolished by PPARα knockdown. In conclusion, this study demonstrates that LNT may ameliorate hepatic steatosis and decrease oxidative stress and apoptosis by activating the PPARα pathway and is a potential drug target for NAFLD.

Background. Many patients with diabetes die from diabetic cardiomyopathy (DCM); however, effective strategies for the prevention or treatment of DCM have not yet been clarified. Methods. Leptin receptor‐deficient (db/db) mice were treated with either the soluble epoxide hydrolase (sEH) inhibitor AUDA or vehicle alone. A virus carrying Nrf2 shRNA was used to manipulate Nrf2 expression in db/db mice. Cardiac structures and functions were analyzed using echocardiography and hemodynamic examinations. Primary cardiomyocytes cultured under high glucose and high fat (HGHF) conditions were used to conduct in vitro loss‐of‐function assays after culture in the presence or absence of AUDA (1 μM). Fluorescence microscopy‐based detection of mCherry‐GFP‐LC3 was performed to assess autophagic flux. Results. The sEH inhibitor AUDA significantly attenuated ventricular remodeling and ameliorated cardiac dysfunction in db/db mice. Interestingly, AUDA upregulated Nrf2 expression and promoted its nuclear translocation in db/db mice and the HGHF‐treated cardiomyocytes. Additionally, AUDA increased autophagy and decreased apoptosis in db/db mice heart. Furthermore, the administration of AUDA promoted autophagic flux and elevated LC3‐II protein level in the presence of bafilomycin A1. However, AUDA‐induced autophagy was abolished, and the antiapoptotic effect was partially inhibited upon Nrf2 knockdown. Conclusion. Our findings suggest that the sEH inhibitor AUDA attenuates cardiac remodeling and dysfunction in DCM via increasing autophagy and reducing apoptosis, which is relevant to activate Nrf2 signaling pathway.

To determine the diagnostic performance of transcranial sonography (TCS) in assessing increased echogenic area of the substantia nigra (SN) in patients with Parkinson's disease (PD). Institutional review board approval was obtained for this retrospective study. A total of 278 PD patients (mean age: 64.7 ± 9.8 y, 100 women) and 300 healthy control patients (mean age: 63.6 ± 9.3 y, 97 women) were referred for TCS assessment of SN hyper-echogenicity (SN+) from June 2016 to December 2018. Two sonographers independently measured the sizes of the echogenic areas of the SN by TCS imaging in both PD patients and healthy controls. The diagnostic sensitivity, specificity and accuracy of TCS imaging were compared between PD patients and healthy controls. Inter-rater agreement was assessed with the Cohen's κ statistic. The sensitivity, specificity and accuracy of readers 1 and 2, respectively, for the identification of SN+ in TCS were 90.3% and 89.6% (251 and 249 of 278), 89.3% and 88.3% (268 and 265 of 300) and 89.8% and 88.9% (519 and 514 of 578). Inter-observer agreement was excellent (к = 0.84). The area under the receiver operating characteristic curve (AUC) for differentiation of PD patients from healthy controls was 0.92 for reader 1 and 0.91 for reader 2. Cutoff values of 0.20 and 0.21 cm2 were derived from the assessments performed by readers 1 and 2, respectively. We defined 0.20 cm2 as the optimal cutoff value because it had a higher AUC. TCS is a promising diagnostic technique and can be very helpful in differentiating PD patients from healthy individuals.

Despite the widespread use of doxorubicin (DOX) in chemotherapy, it can cause cardiotoxicity, which severely limits its potential clinical use. CYP2J2-derived epoxyeicosatrienoic acids (EETs) exert cardioprotective effects by maintaining cardiac homeostasis. The roles and latent mechanisms of EETs in DOX cardiotoxicity remain uncertain. We investigated these aspects using mouse tissue and cell culture models. C57BL/6J mice were injected with rAAV9-CYP2J2 or a control vector via the caudal vein. A five-week intraperitoneal course of DOX (5 mg/kg per week) was administered. After pretreatment with 14,15-EET, H9C2 cells were treated for 24-h with DOX, to use as a cell model to verify the role of EETs in cardiotoxicity in vitro. CYP2J2 overexpression mitigated DOX-induced cardiotoxicity, as shown by the diminished cardiac injury marker levels, improved heart function, reduced oxidative stress, and inhibition of myocardial apoptosis in vivo. These protective roles are associated with the enhancement of antioxidant and anti-apoptotic abilities and the activation of the AMPK pathway. 14,15-EET suppresses DOX-induced oxidative stress, mitochondrial dysfunction, and apoptosis in H9C2 cells. AMPK knockdown partially abolished the cardioprotective effects of 14,15-EET against oxidative damage and apoptosis in DOX-treated cells, suggesting that AMPK is responsible for EET-mediated protection against cardiotoxicity. CYP2J2-derived EETs confer myocardial protection against DOX-induced toxicity by activating the AMPK pathway, which reduces oxidative stress, mitochondrial dysfunction, and apoptosis.

Substantia nigra (SN) hyperechogenicity measured by transcranial sonography (TCS) is a promising biomarker for Parkinson disease (PD). The aim of this study was to explore the diagnostic accuracy of SN hyperechogenicity (SN⁺) for differentiating PD from essential tremor (ET). A total of 119 patients with PD, 106 ET patients and 112 healthy controls that underwent TCS from November 2016 to February 2019 were included in this single-center retrospective case–control study. Two reviewers who were blinded to clinical information independently measured the SN⁺ by TCS imaging. The diagnostic sensitivity, specificity, and accuracy of TCS imaging were evaluated between the PD and healthy controls and between patients with PD and ET. Interrater agreement was assessed with the Cohen κ statistic. TCS imaging of the SN⁺ allowed to differentiate between patients with PD and ET with a sensitivity (91.6% and 90.8%) and specificity (91.5% and 89.6%) for readers 1 and 2, respectively. Interobserver agreement was excellent (к = 0.87). In addition, measurement of the SN⁺ allowed to differentiate between patients with PD and healthy subjects with a sensitivity (91.6% and 90.8%) and specificity (88.4% and 89.3%) for readers 1 and 2, respectively. Interobserver agreement was excellent (к = 0.91). Measurement of SN⁺ on TCS images could be a useful tool to distinguishing patients with PD from those with ET.