Oxidative stress-induced aberrant G9a activation disturbs RE-1-containing neuron-specific genes expression, leading to degeneration in human SH-SY5Y neuroblastoma cells

Oxidative stress-induced neurodegeneration is one of several etiologies underlying neurodegenerative disease. In the present study, we investigated the functional role of histone methyltransferase G9a in oxidative stress-induced degeneration in human SH-SY5Y neuroblastoma cells. Cell viability significantly decreased on H2O2treatment; however, treatment with the G9a inhibitor BIX01294 partially attenuated this effect. The expression of neuron-specific genes also decreased in H2O2 -treated cells; however, it recovered on G9a inhibition. H2O2 -treated cells showed high levels of H3K9me2 (histone H3 demethylated at the lysine 9 residue), which is produced by G9a activation; BIX01294 treatment reduced aberrant activation of G9a.H3K9me2 occupancy of the RE-1 site in neuron-specific genes was significantly increased in H2O2 -treated cells, whereas it was decreased in BIX01294-treated cells. The differentiation of H2O2 -treated cells also recovered on G9a inhibition by BIX01294. Consistent results were observed when used another G9a inhibitor UCN0321. These results demonstrate that oxidative stress induces aberrant activation of G9a, which disturbs the expression of neuron-specific genes and progressively mediates neuronal cell death. Moreover, a G9a inhibitor can lessen aberrant G9a activity and prevent neuronal damage. G9a inhibition may therefore contribute to the prevention of oxidative stress-induced neurodegeneration.

New Biodegradable Drug Delivery System for Patients with Dry Eye

Purpose@#This study aimed to develop a new type of drug delivery system (DDS) for treatment of dry eye. @*Methods@#A new lens-type biodegradable DDS was manufactured using gelatin methacryloly, antibiotics, and conjunctival epithelial cells as bio-inks in a Bio X 3D Bioprinter. Gelatin methacryloly was used as a base, and the conditions were analyzed to maintain the overall shape by using a mixture of 0.1%, 0.15%, and 0.3% hyaluronic acid. In addition, an experiment was conducted to measure the appropriate concentration by evaluating its cytotoxicity according to the concentration of antibiotics mixed therein to prevent infection. The degree of degradation according to the storage temperature and post-processing of the new lens-type biodegradable DDS was measured. @*Results@#Optimal conditions were maintained when using a nozzle pressure of 80 kPa and speed of 4 mm/sec, nozzle pressure of 50 kPa and speed of 3 mm/sec, nozzle pressure of 60 kPa and speed of 8 mm/sec for 0.1%, 0.15%, and 0.3% hyaluronic acid concentrations, respectively. Degradation did not occur at 4°C and all the lenses were degraded at 37°C within 24 hours. In addition, the degradation rate was delayed according to the ultraviolet crosslink treatment time. Tobramycin 1% was used as an antibiotic during manufacture. @*Conclusions@#A new lens-type biodegradable DDS that can control the degree of degradation was designed using a 3-dimentional bioprinter. This DDS will contribute to ease of treatment, protection of the cornea, and regeneration of the epithelium in patients with dry eye.

Oxidative stress-induced aberrant G9a activation disturbs RE-1-containing neuron-specific genes expression, leading to degeneration in human SH-SY5Y neuroblastoma cells

Oxidative stress-induced neurodegeneration is one of several etiologies underlying neurodegenerative disease. In the present study, we investigated the functional role of histone methyltransferase G9a in oxidative stress-induced degeneration in human SH-SY5Y neuroblastoma cells. Cell viability significantly decreased on H2O2treatment; however, treatment with the G9a inhibitor BIX01294 partially attenuated this effect. The expression of neuron-specific genes also decreased in H2O2 -treated cells; however, it recovered on G9a inhibition. H2O2 -treated cells showed high levels of H3K9me2 (histone H3 demethylated at the lysine 9 residue), which is produced by G9a activation; BIX01294 treatment reduced aberrant activation of G9a.H3K9me2 occupancy of the RE-1 site in neuron-specific genes was significantly increased in H2O2 -treated cells, whereas it was decreased in BIX01294-treated cells. The differentiation of H2O2 -treated cells also recovered on G9a inhibition by BIX01294. Consistent results were observed when used another G9a inhibitor UCN0321. These results demonstrate that oxidative stress induces aberrant activation of G9a, which disturbs the expression of neuron-specific genes and progressively mediates neuronal cell death. Moreover, a G9a inhibitor can lessen aberrant G9a activity and prevent neuronal damage. G9a inhibition may therefore contribute to the prevention of oxidative stress-induced neurodegeneration.

A Case of Aggravated Hyperplastic Gastric Polyps after Treatment with Long-term Proton Pump Inhibitors / 영남의대학술지

Hyperplastic gastric polyps (HPPs) are the most common type of gastric polyps. They are assumed to be caused by chronic inflammation and regenerative proliferation, although this has not been clearly investigated yet. Many studies suggested the development of fundic gland polyps and carcinoid during long-term proton pump inhibitor (PPI) therapy, but the relationship between PPIs and HPPs is still unclear. We encountered a patient who showed aggravation of HPPs after long-term use of PPIs. A 58-year-old male patient with liver cirrhosis visited our hospital because of hematemesis. We started PPI medication after confirming esophageal variceal bleeding and duodenal ulcer with blood clot in its base via emergency endoscopy. He took PPIs for three years because of an intractable duodenal ulcer. There was a marked increase in the size of the pre-existing polyps and in the development of new polyps. We presumed that the PPIs caused the aggravation of the HPPs, so we stopped their administration. After five months, the HPPs shrank and the polyps were partially degraded. More prospective studies are needed to investigate the relationship between HPPs and PPIs.

A Case of Idiopathic Eosinophilic Cholecystitis Treated with Steroids / 대한내과학회지

Eosinophilic cholecystitis is a rare disease characterized by transmural leukocyte infiltration composed of more than 90% eosinophils. Eosinophilic cholecystitis is clinically indistinguishable from ordinary cholecystitis, and as a rule it leads to cholecystectomy. We report a case of idiopathic eosinophilic cholecystitis treated with steroids. A 75-year-old woman presented with a classic history of acute cholecystitis and a peripheral eosinophilia of 41.8%. There was no evidence of allergy or parasitic infestation. An abdominal ultrasonography and computed tomography (CT) scan showed an edematous, thickened gallbladder wall, but no gallstones. There was no evidence of eosinophilic infiltration in other organs. Cholecystectomy was not performed because the patient refused surgical management. However, fever, abdominal pain, and peripheral eosinophilia persisted despite antibiotic and conservative therapy. Therefore, we attempted treatment with prednisolone. A week later, the symptoms disappeared and the peripheral eosinophilia normalized.

Praziquantel Treatment of an Eosinophilic Pleuritis Patient Suspected to Be Due to Sparganum Infection / 감염과화학요법

Human sparganosis is caused by the larval tapeworm of genus Spirometra. This parasite commonly invades subcutaneous tissues and muscles. However, infection in the pleural cavity is rare. A 65-year-old male patient, who had undergone surgical excision of subcutaneous masses due to a parasite infection (presumed to have been sparganosis) approximately 10 years ago, showed pleural effusion and peripheral eosinophilia. The anti-sparganum specific IgG antibody levels in the serum and pleural fluid were significantly higher than the normal control levels. Three consecutive doses of praziquantel (75 mg/kg/day) were administered for control of pleural effusion and peripheral eosinophilia. In this patient, sparganosis was suspected, and the probable cause of the infection was ingestion of raw snakes and frogs. Immunoserologic tests using ELISA can be helpful in diagnosis of pleural sparganosis and praziquantel is suggested as an alternative treatment for surgically unresectable cases.

Three Cases of Pseudomembranous Colitis with Hematochezia / 대한소화기내시경학회지

Clostridium difficile is the most common nosocomial pathogen of the gastrointestinal tract. Pseudomembranous colitis occurs as a result of a severe inflammatory response to Clostridium difficile toxins. Pseudomembranous colitis is an increasingly frequent cause of morbidity and mortality among elderly hospitalized patients. Diarrhea is the most common manifestation. According to the literature, stools are almost never grossly bloody, and range from soft and unformed to watery or mucoid in consistency. We now report the cases of three patients with pseudomembranous colitis whose main clinical manifestation was hematochezia.

Classification of Adult Isthmic Spondylolisthesis: Based on the Morphologic Changes of Spinal Canal and Neural Contents by Myelography and CT Scan / 대한척추외과학회지

STUDY DESIGN: We classified adult isthmic spondylolisthesis based on the findings of postmyelographic CT scanning. OBJECTIVES: To propose a new classification that could be used as a useful guideline when evaluating the patient with adult isthmic spondylolisthesis. SUMMARY OF LITERATURE REVIEW: Morphologic changes of the spinal canal and its neural contents in the adult patient with isthmic spondylolisthesis and their relations to radiological variables have not been well described in literature. MATERIALS AND METHODS: 32 adult patients with one level isthmic spondylolisthesis underwent myelography followed by CT scanning. Based on these findings, we classified each patient with four morphologic criteria; 1. dural station I or ll by the location of dural sac, 2. non-compression or compression type by the existence of lateral compression of dural sac. 3. root station I or ll by the location of nerve root, 4. hook or smooth type by the shape of spinal canal. Subsequent statistical analyses to assess the relationships between our newly developed classification and clinical variables were tested by SPSS software. RESULTS: Dural station correlated positively with percent slip(rpb=0.39; p=0.026). Patient age was closely related to the lateral compression(rpb=0.54, p<0.01) which consequently decreased transverse diameter of dural sac(rpb=-0.68, p<0.01). Both dural station and lateral compression were important in the prediction of the extent of the dural involvement. Root station of the smooth type correlated positively with percent slip(reb=0.47: p=0.038), while that of the hook type did not. Consequently, nerve root of the hook type entered neural foramen under the pedicle, whereas that of the smooth type entered at various locations depending on the degrees of percent slip. Depth of lateral recess was significantly less in the hook type than in the smooth type(p<0.01). Stretching of the nerve root, produced by posterior migration of the nerve root, was observed only in the smooth type. CONCLUSIONS: We strongly recommend the use of our classification because it is easy to apply and has a high correlation with radiological variables.