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Natural pentacyclic triterpenoid oleanolic acid (OA) is used as an over‐the‐counter drug for acute and chronic hepatitis. However, clinical use of OA‐containing herbal medicines has been reported to cause cholestasis, and the specific mechanism is unknown. The purpose of this study was to explore how OA causes cholestatic liver injury via the AMP‐activated protein kinase (AMPK)‐farnesoid X receptor (FXR) pathway. In animal experiments, it was found that OA treatment activated AMPK and decreased FXR and bile acid efflux transport proteins expression. When intervened with the specific inhibitor Compound C (CC), it was observed that AMPK activation was inhibited, the reduction of FXR and bile acid efflux transport protein expression was effectively alleviated, serum biochemical indicators were significantly reduced, and liver pathological damage brought about by OA was effectively ameliorated. In addition, OA was found to downregulate the expression of FXR and bile acid efflux transport proteins by activating the ERK1/2‐LKB1‐AMPK pathway in cellular experiments. The ERK1/2 inhibitor U0126 was used to pretreat primary hepatocytes, and this drastically reduced the phosphorylation levels of LKB1 and AMPK. The inhibition effects of OA on FXR and bile acid efflux transport proteins were also effectively alleviated after pretreatment with CC. In addition, OA‐induced downregulation of FXR gene and protein expression levels was significantly prevented after silencing AMPKα1 expression in AML12 cells. Our study demonstrated that OA inhibited FXR and bile acid efflux transporters through the activation of AMPK, thus leading to cholestatic liver injury. Oleanolic acid (OA) is used as an over‐the‐counter drug for the treatment of liver diseases, but clinical use of OA‐containing herbal medicines can lead to cholestasis. In this study, OA was found to induce liver injury by activating AMPK phosphorylation through the ERK1/2‐LKB1 pathway and inhibiting FXR and its downstream targets. Silencing of AMPKα1 in cells attenuated OA‐induced FXR inhibition. Pharmacological inhibition of AMPK in cells and animals has a protective effect against OA‐induced liver injury. [ABSTRACT FROM AUTHOR]

Abstract Background The study aimed to prospectively observe the clinical and neuroimaging features of pontine infarction with pure motor hemiparesis (PMH) or hemiplegia at early stage. Methods In 118 consecutive selected patients with the first-ever ischemic stroke within 6 hours after onset, fifty of them presented with PMH or hemiplegia and had negative acute computed tomography (CT) scans, then magnetic resonance imaging (MRI) confirmed the corresponding infarcts in pons or cerebrum. The clinical and neuroimaging features of the pontine infarctions were compared with those of cerebral infarctions. Results The pontine infarction with PMH or hemiplegia accounted for 10.2% (12/118) of all first-ever ischemic stroke patients and 24% (12/50) of the patients with both PMH or hemiplegia and acute negative CT scans. Compared to the patients with cerebral infarction, the patients with pontine infarction had more frequency of diabetes mellitus (50.0% vs 5.3%, P = 0.001), nonvertiginous dizziness at onset (58.3% vs 21.1%, P = 0.036) and a progressive course (33.3% vs 2.6%, P = 0.011). Conclusion The pontine infarction may present as PMH or hemiplegia with more frequency of nonvertiginous dizziness, a progressive course and diabetes mellitus. MRI can confirm the infarct location in the basal pons at early stage after stroke onset.

Background: Stroke, especially ischemic stroke, is a leading disease associated with death and long-term disability with limited therapeutic options. Neuronal death caused by vascular impairment, programmed cell death and neuroinflammation has been proven to be associated with increased stroke severity and poor stroke recovery. In light of this, a development of neuroprotective drugs targeting injured neurons is urgently needed for stroke treatment. Netrin-1, known as a bifunctional molecule, was originally described to mediate the repulsion or attraction of axonal growth by interacting with its different receptors. Importantly, accumulating evidence has shown that netrin-1 can manifest its beneficial functions to brain tissue repair and neural regeneration in different neurological disease models., Objective: In this review, we focus on the implications of netrin-1 and its possibly involved pathways on neuroprotection after ischemic stroke, through which a better understanding of the underlying mechanisms of netrin-1 may pave the way to novel treatments., Methods: Peer-reviewed literature was recruited by searching databases of PubMed, Scopus, Embase, and Web of Science till the year 2021., Conclusion: There has been certain evidence to support the neuroprotective function of netrin-1 by regulating angiogenesis, autophagy, apoptosis and neuroinflammation after stroke. Netrin-1 may be a promising drug candidate in reducing stroke severity and improving outcomes., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Idiopathic hypertrophic cranial pachymeningitis (IHCP) is a very infrequent disorder that causes a localized or diffuse thickening of the dura mater. The main clinical features of IHCP at presentation are headache, cranial nerve involvement, ataxia, and seizures. Transient ischemic attacks (TIAs) have not previously been reported as a main clinical manifestation. We present a case with TIA as the main clinical manifestation and investigated the treatment of the case., Case Report: A 33-year-old male complaining of recurrent left hemiparesis for 22 days was admitted into our hospital. The clinical characteristics and CT, MRI, and pathological data were investigated carefully. IHCP was diagnosed and pulse corticosteroid therapy was used to treat this case. Headache, neck pain and recurrent episodes of weakness and numbness in the left limbs were the main clinical manifestations. CT and MRI revealed thickening of the dura along the falx and tentorium. Meningeal biopsy showed diffused thickening of the dura, consisting of collagen in concentric form with inflammatory cell infiltrating and fibrinoid necrosis, confirmed to be dura mater by histopathological examination. Treatment with an antiplatelet drug, low molecular heparin and herbs did not prevent the attacks. Pulse corticosteroid therapy was used and good efficiency was achieved., Conclusions: Recurrent episodes of TIAs can be the main clinical manifestations of IHCP, and pulse corticosteroid therapy was effective.