Nonalcoholic fatty liver disease (NAFLD) is a major public health problem with comorbidities including obesity and dyslipidemia. Although the manifestations of NAFLD range from simple steatosis to non-alcoholic steatohepatitis, these may potentially give rise to liver cirrhosis and hepatocellular carcinoma. However, the mechanisms underlying NAFLD, and the factors that determine the individual risk of disease progression, remain poorly known. The most obvious clinicopathological characteristic of NAFLD is hepatic lipid accumulation and subsequent inflammation. In hepatocytes, the endoplasmic reticulum (ER) is a critical site of protein synthesis, detoxification, lipid and glucose metabolism, and Ca2+ homeostasis; the ER is involved in NAFLD pathogenesis. Hepatic accumulation of lipids stresses the ER; this activates the unfolded protein response (UPR), which is classically viewed as an adaptive pathway that maintains ER homeostasis. Recent studies have revealed that UPR sensors regulate hepatic steatosis and the cellular response to lipotoxic stress. Therefore, the basic mechanisms of ER stress and UPR induction are of great interest for understanding the pathogenesis of NAFLD. The present review focuses on the roles played by ER stress and the UPR in NAFLD pathogenesis.

Nonalcoholic fatty liver disease (NAFLD) is a major public health problem with comorbidities including obesity and dyslipidemia. Although the manifestations of NAFLD range from simple steatosis to non-alcoholic steatohepatitis, these may potentially give rise to liver cirrhosis and hepatocellular carcinoma. However, the mechanisms underlying NAFLD, and the factors that determine the individual risk of disease progression, remain poorly known. The most obvious clinicopathological characteristic of NAFLD is hepatic lipid accumulation and subsequent inflammation. In hepatocytes, the endoplasmic reticulum (ER) is a critical site of protein synthesis, detoxification, lipid and glucose metabolism, and Ca2+ homeostasis; the ER is involved in NAFLD pathogenesis. Hepatic accumulation of lipids stresses the ER; this activates the unfolded protein response (UPR), which is classically viewed as an adaptive pathway that maintains ER homeostasis. Recent studies have revealed that UPR sensors regulate hepatic steatosis and the cellular response to lipotoxic stress. Therefore, the basic mechanisms of ER stress and UPR induction are of great interest for understanding the pathogenesis of NAFLD. The present review focuses on the roles played by ER stress and the UPR in NAFLD pathogenesis.

No abstract available.
Carcinoma, Hepatocellular* ; Catheter Ablation* ; Neoplasm Metastasis*

No abstract available.
Animals ; Rats* ; Reperfusion*

In this study, the ontogeny of the dopamine D1 and D2 receptors on fetal rat retina was investigated by using in situ hybridization technique. The expression of the D1 and D2 receptor mRNAs showed different pattern of appearance, distribution and density. At gestational day(GD) 13.5, D1 receptor was first detected in neuroepithelium of the retina. Both D1 and D2 receptors were detected at GD 15.5 in the ventricular layer and ganglion cell layer of developing retina of the rat, and D1 receptor showed more strong density than that of D2 receptor. At GD 17.5, Both D1 and D2 receptors were detected in the ganglion cell layer, ventricular layer and pigment epithelium. The labelling density of D1 receptor was higher than that of D2 receptor. At GD 19.5, both D1 and D2 receptors were additionally detected in the optic nuclear layer and plexiform layer. These results imply that D1 and D2 receptor may mediate different important function of the retina.
Animals ; Dopamine* ; Epithelium ; Ganglion Cysts ; In Situ Hybridization ; Rats* ; Retina* ; RNA, Messenger*

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. The only curative treatment modalities for HCC are surgery, percutaneous ablation, and liver transplantation. Unfortunately, the majority of patients have unresectable disease at diagnosis. Therefore, effective treatment options are needed for patients with advanced HCC. The current standard treatment for patients with advanced HCC, according to the Barcelona Clinic Liver Cancer staging system, is the multikinase inhibitor sorafenib. Other alternative therapies are required, due to the limited treatment response to, and tolerance of, this molecular target agent. Clinical trials of hepatic artery infusion chemotherapy, radioembolization, and multimodal treatments have shown favorable results in advanced HCC patients. This article introduces new treatment modalities for advanced HCC and discusses future therapeutic possibilities.
Antineoplastic Agents/administration & dosage/*therapeutic use ; Carcinoma, Hepatocellular/enzymology/pathology/*therapy ; Combined Modality Therapy ; Embolization, Therapeutic/*methods ; Hepatic Artery ; Humans ; Infusions, Intra-Arterial ; Liver Neoplasms/enzymology/pathology/*therapy ; Molecular Targeted Therapy ; Niacinamide/analogs & derivatives/therapeutic use ; Phenylurea Compounds/therapeutic use ; Protein Kinase Inhibitors/therapeutic use ; Radiopharmaceuticals/therapeutic use ; Signal Transduction/drug effects ; Treatment Outcome

Syphilitic aortitis, passing out of our mind, is the most common systemic manifestation of late syphilis and is more typically manifestated 10 to 30 years afterward. This diagnosis has been made less frequently in recent decades than in the past, because of public awareness of syphilis and screening program. Treponema pallidum lodge within vasa vasorum, especially ascending aorta cause the histologic changes, which are responsible for the three major forms of symptomatic cardiovascular syphilis, including aortic insufficiency, coronary ostial stenosis, and aortic aneurysm. We experienced a case of syphilitic aortitis with aortic insufficiency and aortic aneurysm in a 48-year-old man presented with progressive dyspnea. Echocardiography, chest CT, and later surgical correction were performed and surgical specimen revealed the histologic finding consistent with syphilitic aortitis. We report this case with a review of the literature.
Aorta ; Aortic Aneurysm* ; Aortitis ; Constriction, Pathologic ; Diagnosis ; Dyspnea ; Echocardiography ; Humans ; Mass Screening ; Middle Aged ; Syphilis ; Syphilis, Cardiovascular* ; Tomography, X-Ray Computed ; Treponema pallidum ; Vasa Vasorum

Doxorubicin has characteristic chemomyectomy effect of the eyelid without disturbing other eyelid structures, but the major side effect of doxorubicin is the potential for eyelid skin injury as a result of the drug's toxicity in both animal and clinical studies. Verapamil may be used to reduce the dose of doxorubicin and the number of injections that would amplify the toxic effects of doxorubicin. This study was performed to determine whether there is an increase in the toxic effect of the doxorubicin as a result of verapamil pretreatment of the muscle. After 0.5mg, 1.0mg, and 2.0mg doxorubicin was injected in lower eyelids of each group, and equal dose of doxorubicin was injected fo11owing 1.0mg of verapamil injection in lower eyelid of each group, muscle cell loss were measured by light microscopy and side effect was observed. In verapamil and doxorubicin injection group, there was significant differences in the amount of preseptal muscle and even in the pretarsal muscle than the doxorubicin injection group in all doxorubicin doses. Verapamil, injected with a range of doses of doxorubicin, caused suhstantia11y increased muscle loss in the eyelid, compared with injection of doxorubicin alone. Skin ulceration, entropion or ectropion were not visible. Clinically, verapamil cotreatment might be useful to decrease the dose of doxorubicin injected and/or the total number of injections.
Animals ; Doxorubicin* ; Ectropion ; Entropion ; Eyelids ; Microscopy ; Muscle Cells ; Skin ; Skin Ulcer ; Verapamil*

BACKGROUND/AIMS: The treatment strategy for hepatitis C virus (HCV) has been changing rapidly since the introduction of direct-acting antivirals such as daclatasvir (DCV) and asunaprevir (ASV). We evaluated the efficacy and safety of DCV and ASV for HCV in real-life practice. METHODS: Patients were treated with 60 mg of DCV once daily plus 200 mg of ASV twice daily for 24 weeks, and followed for 12 weeks. The primary endpoint was a sustained virological response at 12 weeks after treatment (SVR12) and safety. RESULTS: This retrospective study included eight patients with chronic HCV genotype 1b infection. All of the enrolled patients were diagnosed with liver cirrhosis, and their mean age was 65.75 years. One patient was a nonresponder and two patients relapsed with previous pegylated interferon (PegIFN) and ribavirin (RBV) treatment. None of the patient showed NS5A mutation. An SVR12 was achieved in 88% of cases by the DCV and ASV combination therapy. The serum transaminase level and the aspartate-aminotransferase-to-platelet ratio were improved after the treatment. DCV and ASV were well tolerated in most of the patients, with treatment discontinuation due to adverse events (elevated liver enzyme and decompensation) occurring in two patients. CONCLUSIONS: In this study, combination of DCV and ASV treatment achieved a high sustained virological response with few adverse events even in those with cirrhosis, advanced age, and nonresponse/relapse to previous interferon-based therapy. Close monitoring of safety issues may be necessary when treating chronic HCV patients receiving DCV and ASV, especially in older patient and those with cirrhosis.
Aged ; Alanine Transaminase/blood ; Antiviral Agents/*therapeutic use ; Aspartate Aminotransferases/blood ; Drug Administration Schedule ; Drug Resistance, Viral ; Drug Therapy, Combination ; Female ; Genotype ; Hepacivirus/*genetics/isolation & purification ; Hepatitis C, Chronic/complications/*drug therapy/virology ; Humans ; Imidazoles/*therapeutic use ; Isoquinolines/*therapeutic use ; Liver/diagnostic imaging ; Liver Cirrhosis/complications ; Male ; Middle Aged ; RNA, Viral/blood ; Retrospective Studies ; Sulfonamides/*therapeutic use ; Treatment Outcome