Silencing MFN2 Drives WNT/β-catenin Nucleation to Reduce Sorafenib Sensitivity in Hepatocellular Carcinoma Cells

Objective Mitofusin-2(MFN2)is a mitochondrial membrane protein that plays a critical role in regulating mitochondrial fusion and cellular metabolism.To further elucidate the impact of MFN2,this study aimed to investigate its significance on hepatocellular carcinoma(HCC)cell function and its potential role in mediating chemosensitivity.Methods This study investigated the effects of silencing and overexpressing MFN2 on the survival,proliferation,invasion and migration abilities,and sorafenib resistance of MHCC97-L HCC cells.Additional experiments were conducted using XAV939(aβ-catenin inhibitor)and HLY78(aβ-catenin activator)to further validate these findings.Results Silencing MFN2 significantly promoted the survival and proliferation of MHCC97-L cells,enhanced their invasion and migration capacities,increased the IC50 of sorafenib,reduced the percentage of TUNEL-positive cells,and decreased the expression of proapoptotic proteins.Additionally,silencing MFN2 markedly induced the nuclear translocation ofβ-catenin,increasedβ-catenin acetylation levels and enhanced the expression of the downstream regulatory proteins Snail1 and Vimentin while inhibiting E-cadherin expression.Conversely,overexpressing MFN2 reversed the effects observed in MHCC97-L cells mentioned above.The results confirmed that silencing MFN2 activated theβ-catenin/epithelial-mesenchymal transition(EMT)pathway and reduced the sensitivity of cells to sorafenib,which could be reversed by XAV939 treatment.Conversely,overexpression of MFN2 inhibited theβ-catenin/EMT pathway and increased the sensitivity of cells to sorafenib,which could be altered by HLY78.Conclusion Low expression of MFN2 in HCC cells promotes the nuclear translocation ofβ-catenin,thereby activating the EMT pathway and mediating resistance to sorafenib.

Transjugular intrahepatic portosystemic shunt plus embolization for bleeding esophagojejunal varices after total gastrectomy

A 64-year-old man was admitted to our hospital with hematemesis and melena.Six years ago,he had undergone total gastrectomy with Roux-en-Y esophagojejunostomy for gastric cancer.Endoscopic examination revealed varicose veins at the anastomotic sites with cherry-red spots and hemorrhage.Abdominal computed tomography showed that the varices were supplied by a dilated jejunal vein.Transjugular intrahepatic portosystemic shunt(TIPS)and variceal embolization were performed.There were no major complications or episodes of bleeding during the three-month follow-up.We conclude that TIPS in combination with varices obliteration is an effective alternative method for treatment of ruptured esophagojejunal varices after total gastrectomy.

Delayed diagnosis of prosopagnosia following a hemorrhagic stroke in an elderly man:A case report

BACKGROUND Acquired prosopagnosia is a rare condition characterized by the loss of familiarity with previously known faces and the inability to recognize new ones.It usually occurs after the onset of brain lesions such as in a stroke.The initial identification of prosopagnosia generally relies on a patient’s self-report,which can be challenging if it lacks an associated chief complaint.There were few cases of prosopagnosia presenting purely as eye symptoms in the previous literature confirmed by functional magnetic resonance imaging(MRI).CASE SUMMARY We present a case of delayed diagnosis of prosopagnosia after a right hemisphere stroke in an elderly man whose chief complaint was persistent and progressive"blurred vision"without facial recognition impairment.Ophthalmic tests revealed a homonymous left upper quadrantanopia,with normal visual acuity.He was found by accident to barely recognize familiar faces.The patient showed severe deficit in face recognition and perception tests,and mild memory loss in neuropsychological assessments.Further functional MRI revealed the visual recognition deficits were face-specific.After behavioral intervention,the patient started to rely on other cues to compensate for poor facial recognition.His prosopagnosia showed no obvious improvement eight months after the stroke,which had negative impact on his social network.CONCLUSION Our case demonstrates that the presentation of prosopagnosia can be atypical,and visual difficulties might be a clinical manifestation solely of prosopagnosia,which emphasizes the importance of routinely considering face recognition impairment among elderly patients with brain lesions.