Exenatide has a better hepatic-protective effect than intensive insulin therapy and perhaps represents a unique option for adjunctive therapy for patients with obesity, non-alcoholic fatty liver disease with elevated liver enzymes and T2D.

Mitophagy is essential for cellular homeostasis but the regulatory mechanism is largely unknown. Here we report that the kinase Jnk2 is required for stress-induced mitophagy. Jnk2 promoted ubiquitination and proteasomal degradation of small mitochondrial form of ARF (smARF). Loss of Jnk2 led to accumulation of smARF, which in turn induced excessive autophagic activity, resulting in lysosomal degradation of the mitophagy adaptor p62 in the steady state. The depletion of p62 prevented Jnk2-deficient cells from mounting mitophagy upon stress. Jnk2-deficient mice displayed defective mitophagy, resulting in tissue damage under hypoxic stress, as well as hyperactivation of inflammasome and increased mortality in sepsis. Our finding defines a unique mechanism of maintaining immune homeostasis that protects the host from tissue damage and mortality.

A wide range of microalbuminuria cutoff values are currently used for diagnosing the early stage of nephropathy in type 2 diabetes (T2D). This study analyzed the relationships between oxidant and antioxidant markers of nephropathy and the severity of microalbuminuria. The study included 50 healthy controls (Group 1), 50 diabetic patients with no nephropathy (Group 2), 50 diabetic patients with nephropathy and a urinary albumin excretion (UAE) of 30–200 mg/24 h (Group 3), and 50 diabetic patients with UAE 200–300 mg/24 h (Group 4). Serum nitrotyrosine, conjugated dienes, 8-hydroxy-2′-deoxyguanosine (8-OHdG), superoxide dismutase (SOD), and total antioxidant capacity (T-AOC) levels were determined. Oxidative stress is increased in the early stage of nephropathy in patients with T2D. There was a significant correlation between the extent of microalbuminuria and markers of oxidative stress. Multiple linear regression analysis identified lipid oxidative stress as a possible independent marker for evaluating the degree of renal damage in diabetic nephropathy. Stratifying microalbuminuria values during the early stage of nephropathy might be an important factor in facilitating earlier and more specific interventions.

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Background and Purpose: The utilization of flow diversion for ruptured intracerebral aneurysms (IAs) is still limited. We aimed to demonstrate our multicenter experience using the pipeline embolization device (PED) for ruptured IAs that were difficult to treat by clipping and coiling.Methods: Thirty-eight patients with ruptured IAs who underwent PED treatment from 2015 to 2020 were retrospectively reviewed. Factors associated with procedure-related stroke (ischemic and hemorrhagic) and clinical and angiography outcomes were analyzed.Results: There were 14 (36.8%) saccular IAs, 12 (31.6%) blister-like IAs, and 12 (31.6%) dissecting IAs. Perforator involvement was noted in 10 (26.3%) IAs. Early PED placement ( ≤ 15 days) and adjunctive coiling treatment were performed in 27 (71.1%) and 22 (57.9%) cases, respectively. The overall rate of stroke-related complications was 31.6% (12/38) (including rates of 10.5% for procedure-related hemorrhagic complications and 15.8% for procedure-related infarction). The mortality rate was 13.2% (5/38), and 84.2% of patients (32/38) had favorable outcomes. Thirty-two (84.2%) patients underwent follow-up angiographic evaluations; of these, 84.4% (27 patients) had complete occlusion and 15.6% had incomplete obliteration. Multivariate analysis revealed that early PED placement was not associated with a high risk of procedure-related stroke or an unfavorable outcome. Adjunctive coiling exhibited an association with procedure-related stroke (p = 0.073). Procedure-related hemorrhagic complications were significantly associated with an unfavorable outcome (p = 0.003). Immediate contrast stasis in the venous phase was associated with complete occlusion during follow-up (p = 0.050).Conclusion: The PED is a feasible and effective treatment to prevent rebleeding and achieve aneurysm occlusion, but it is associated with a substantial risk of periprocedural hemorrhage and ischemic complications in acute ruptured IAs. Therefore, the PED should be used selectively for acutely ruptured IAs. Additionally, adjunctive coiling might increase procedure-related stroke; however, it may reduce aneurysm rebleeding in acutely ruptured IAs. Patients with immediate contrast stasis in the venous phase were more likely to achieve total occlusion. A prospective study with a larger sample size should be performed to verify our results.

Background and PurposeAneurysm wall enhancement (AWE) on vessel wall magnetic resonance imaging has been suggested as a marker of the unstable status of intracranial aneurysm (IA) and may predict IA rupture risk. However, the role of abnormal hemodynamics in unruptured IAs with AWE remains poorly understood. This study aimed to determine the association between abnormal hemodynamics and AWE in unruptured middle cerebral artery (MCA) aneurysms.MethodsA total of 28 patients with 32 bifurcation aneurysms of the middle cerebral artery>3mm in size were retrospectively selected for this study. Vessel wall magnetic resonance images were reviewed, and the AWE pattern of each aneurysm was classified as no AWE, partial AWE, and circumferential AWE. Computational fluid dynamics were used to calculate the hemodynamic variables of each aneurysm. Univariate and multivariate analyses investigated the association between AWE and hemodynamic variables.ResultsAWE was present in 13 aneurysms (40.6%), with 7 (21.9%) showing partial AWE and 6 (18.7%) showing circumferential AWE. Kruskal–Wallis H analysis revealed that hemodynamic variables including wall shear stress (WSS), oscillatory shear index, aneurysm pressure (AP), relative residence time, and low shear area (LSA) were significantly associated with AWE (p < 0.05). Further ordinal logistic regression analysis found that WSS was the only factor with a significant association with AWE (p = 0.048); similar trends were identified for LSA (p = 0.055) and AP (p = 0.058). Spearman's correlation analysis showed that AWE was negatively correlated with WSS (rs = −0.622, p < 0.001) and AP (rs = −0.535, p = 0.002) but positively correlated with LSA (rs = 0.774, p < 0.001).ConclusionLow wall shear stress, low aneurysm pressure, and increased low shear area were associated with aneurysm wall enhancement on vessel wall magnetic resonance imaging in unruptured cerebral aneurysms. These abnormal hemodynamic parameters may induce inflammation and cause aneurysm wall enhancement. However, the association between these parameters and their underlying pathological mechanisms requires further investigation.