Identification of signature gene set as highly accurate determination of metabolic dysfunction-associated steatotic liver disease progression

Background/Aims@#Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by fat accumulation in the liver. MASLD encompasses both steatosis and MASH. Since MASH can lead to cirrhosis and liver cancer, steatosis and MASH must be distinguished during patient treatment. Here, we investigate the genomes, epigenomes, and transcriptomes of MASLD patients to identify signature gene set for more accurate tracking of MASLD progression. @*Methods@#Biopsy-tissue and blood samples from patients with 134 MASLD, comprising 60 steatosis and 74 MASH patients were performed omics analysis. SVM learning algorithm were used to calculate most predictive features. Linear regression was applied to find signature gene set that distinguish the stage of MASLD and to validate their application into independent cohort of MASLD. @*Results@#After performing WGS, WES, WGBS, and total RNA-seq on 134 biopsy samples from confirmed MASLD patients, we provided 1,955 MASLD-associated features, out of 3,176 somatic variant callings, 58 DMRs, and 1,393 DEGs that track MASLD progression. Then, we used a SVM learning algorithm to analyze the data and select the most predictive features. Using linear regression, we identified a signature gene set capable of differentiating the various stages of MASLD and verified it in different independent cohorts of MASLD and a liver cancer cohort. @*Conclusions@#We identified a signature gene set (i.e., CAPG, HYAL3, WIPI1, TREM2, SPP1, and RNASE6) with strong potential as a panel of diagnostic genes of MASLD-associated disease.

The preventive effect of Gastrodia elata Blume extract on vancomycin‑induced acute kidney injury in rats / 한국실험동물학회지

Background@#Gastrodia elata Blume (GEB), a traditional medicinal herb, has been reported to have pharmacological effect including protection against liver, neuron and kidney toxicity. However, explanation of its underlying mecha‑ nisms remains a great challenge. This study investigated the protective effects of GEB extract on vancomycin (VAN)-induced nephrotoxicity in rats and underlying mechanisms with emphasis on the anti-oxidative stress, anti-inflam‑ mation and anti-apoptosis. The male Sprague-Dawley rats were randomly divided three groups: control (CON) group, VAN group and GEB group with duration of 14 days. @*Results@#The kidney weight and the serum levels of blood urea nitrogen and creatinine in the GEB group were lower than the VAN group. Histological analysis using hematoxylin & eosin and periodic acid Schiff staining revealed pathological changes of the VAN group. Immunohistochemical analysis revealed that the expression levels of N-acetyl-D-glucosaminidase, myeloperoxidase and tumor necrosis factor-alpha in the GEB group were decreased when compared with the VAN group. The number of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive cells, phosphohistone and malondialdehyde levels were lower in the GEB group than VAN group.The levels of total glutathione in the GEB group were higher than the VAN group. @*Conclusions@#The findings of this study suggested that GEB extract prevents VAN-induced renal tissue damage through anti-oxidation, anti-inflammation and anti-apoptosis.

A Case of Neurosyphilis Presenting as a Stroke in a Patient with Human Immunodeficiency Virus Infection / 대한내과학회지

While the neurologic manifestations of syphilis are diverse, stroke is a rare initial manifestation. We report a human immunodeficiency virus (HIV)-positive patient whose neurosyphilis presented as a stroke. A 42-year-old male visited the emergency room due to decreased mental functioning. Brain magnetic resonance imaging showed acute infarct on the left frontal, temporal, and parietal lobes. A serum Venereal Disease Research Laboratory (VDRL) test was positive. ELISA for HIV antibody and Western blot assays revealed he was infected with HIV. The cerebrospinal fluid (CSF) VDRL test was positive and protein was increased. The patient was treated with heparization and penicillin G for 14 days. His mental status improved with treatment, and CSF protein and VDRL titers were also decreased 3 months after treatment.

Effects of Polymorphisms of Innate Immunity Genes and Environmental Factors on the Risk of Noncardia Gastric Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Increasing evidence suggests that polymorphisms in innate immunity genes are associated with Helicobacter pylori-induced inflammation and may influence susceptibility in developing noncardia gastric cancer. Therefore, we investigate the effect of polymorphisms of innate immunity genes and interactions with environmental factors in the Korean population. MATERIALS AND METHODS: We genotyped four polymorphisms of TLR2 (rs1898830), TLR4 (rs10983755 and rs10759932), and CD14 (rs2569190) in a case-control study of 487 noncardia gastric cancer patients and 487 sex- and age-matched healthy controls. Polytomous logistic regression models were used to detect the effects of genetic polymorphisms and environmental factors, which were stratified by the histological type of gastric cancer. RESULTS: TLR4 rs10983755 A carriers were found to have higher risk of intestinal-type noncarida gastric cancer than G homozygotes (odds ratio [OR], 1.41; 95% confidence interval [CI], 1.01 to 1.97), but other genetic variants showed no association with the risk of noncardia gastric cancer. Among H. pylori-positive participants, smokers carrying TLR4 rs10983755 A had a higher risk of intestinal-type gastric cancer than nonsmoking TLR4 rs10983755 G homozygotes (OR, 4.28; 95% CI, 2.12 to 8.64). In addition, compared with tap water, other drinking water sources during childhood were found to be associated with the elevated risk of intestinal-type gastric cancer, and these associations were slightly stronger among TLR4 rs10983755 A carriers. CONCLUSION: The genetic polymorphisms of innate immunity genes are associated with the development of intestinal-type noncardia gastric cancer and these associations may differ in accordance to an exposure to certain environmental factors.

Association Study between Folate Pathway Gene Single Nucleotide Polymorphisms and Gastric Cancer in Koreans

Gastric cancer is ranked as the most common cancer in Koreans. A recent molecular biological study about the folate pathway gene revealed the correlation with a couple of cancer types. In the folate pathway, several genes are involved, including methylenetetrahydrofolate reductase (MTHFR), methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR), and methyltetrahydrofolate-homocysteine methyltransferase (MTR). The MTHFR gene has been reported several times for the correlation with gastric cancer risk. However, the association of the MTRR or MTR gene has not been reported to date. In this study, we investigated the association between the single nucleotide polymorphisms (SNPs) of the MTHFR, MTRR, and MTR genes and the risk of gastric cancer in Koreans. To identify the genetic association with gastric cancer, we selected 17 SNPs sites in folate pathway-associated genes of MTHFR, MTR, and MTRR and tested in 1,261 gastric cancer patients and 375 healthy controls. By genotype analysis, estimating odds ratios and 95% confidence intervals (CI), rs1801394 in the MTRR gene showed increased risk for gastric cacner, with statistical significance both in the codominant model (odds ratio [OR], 1.39; 95% CI, 1.04 to 1.85) and dominant model (OR, 1.34; 95% CI, 1.02 to 1.75). Especially, in the obese group (body mass index > or = 25 kg/m2), the codominant (OR, 9.08; 95% CI, 1.01 to 94.59) and recessive model (OR, 3.72; 95% CI, 0.92 to 16.59) showed dramatically increased risk (p < 0.05). In conclusion, rs1801394 in the MTRR gene is associated with gastric cancer risk, and its functional significance need to be validated.

Identification of genes underlying different methylation profiles in refractory anemia with excess blast and refractory cytopenia with multilineage dysplasia in myelodysplastic syndrome

BACKGROUND: Myelodysplastic syndrome (MDS) is a preleukemic condition that transforms into acute myeloid leukemia. However, the genetic events underlying this transformation remain poorly understood. Aberrant DNA methylation may play a causative role in the disease and its prognosis. Thus, we compared the DNA methylation profiles in refractory anemia with excess blast (RAEB) to those in refractory cytopenia with multilineage dysplasia (RCMD). METHODS: Bone marrow samples were collected from 20 patients with primary MDS (9 with RAEB and 11 with RCMD), and peripheral blood samples were collected from 4 healthy controls. These samples were assessed using a commercial whole genome-wide methylation assay. Methylation-specific polymerase chain reaction (PCR) was used to detect the methylation of candidate gene promoters in RAEB and RCMD. RESULTS: Microarray data revealed significant hypermethylation in 69 genes within RAEB but not RCMD. Candidate genes were mapped to 5 different networks, and network 1 had the highest score due to its involvement in gene expression, cancer, and cell cycle. Five genes (GSTM5, BIK, CENPH, RERG, and ANGPTL2) were associated with malignant disease progression. Among them, the methylated promoter pairs of GSTM5 (55.5% and 20%), BIK (20% and 0%), and ANGPTL2 (44.4% and 10%) were observed more frequently in RAEB. CONCLUSION: DNA methylation of GSTM5, BIK, and ANGPTL2 may induce epigenetic silencing and contribute to the increasing blasts and resulting MDS progression; however, the functions of these genes were not determined. Further study focusing on epigenetic silencing using various detection modalities is required.

Neurolymphomatosis in a patient with T-cell non-Hodgkin's lymphoma / 대한내과학회지

Neurolymphomatosis, defined as a selective infiltration of lymphoma cells into cranial nerves, peripheral nerves and nerve roots, is a rarely recognized manifestation of lymphoma. Its characteristic symptoms are often overlooked or mistaken for other conditions, such as a peripheral polyneuropathy, due to chemotherapeutic agents or clinical findings of metastatic lesions in the central nervous system. Recently, neurolymphomatosis has been increasingly recognized using magnetic resonance imaging and positron emission tomography-computed tomography. We present a case of neurolymphomatosis manifesting as peripheral mononeuropathy in a patient with T-cell non-Hodgkin's lymphoma.

A Case of Bilateral Emphysematous Pyelitis in a Diabetic End-stage Renal Disease Patient Undergoing Peritoneal Dialysis Therapy / 대한신장학회지

Emphysematous pyelitis is uniquely characterized by gas-forming infection restricted to the renal collecting system. This disease entity is uncommon, and shows preferred occurrence in patients with diabetes mellitus or urinary tract obstruction. We report a case of bilateral emphysematous pyelitis in a diabetic end-stage renal disease patient undergoing peritoneal dialysis therapy. The patient was treated by medical treatment only and then recovered from infection, and she has maintained peritoneal dialysis until today. The authors report this case as a successful medical treatment for emphysematous pyelitis accompanying multiple risk factors, such as diabetes mellitus, amorphous medullary kidney stones, and even underlying maintaining peritoneal dialysis.

A Case of Bell's Palsy with Narrowing of the Palpebral Fissure

Widened palpebral fissure has been regarded as one of the hallmarks of Bell's palsy. However, the palpebral fissure on the affected side may be narrower than that of the unaffected side. The narrowing of the palpebral fissure has been often thought as a sign caused by weakness of the levator palpebrae and Muller's muscles. However, weakness of the frontal muscle may cause drooping of the eyebrow, resulting in the narrowing of the palpebral fissure. We describe a patient of Bell's palsy with a narrowing of the palpebral fissure.

Clinical experience of adverse drug reaction in gadolinium-DTPA enhancement of MRI

Gadopentetate dimeglumine(Gd-DTPA) has low toxicity and good tolerance and it is said that the observed adverse drug reaction of Gd-DTPA is compatible to those of iodinated nonionic contrast media. The overall incidence of adverse drug reaction of Gd-DTPA is even lower than those of iodinated nonionic contrast media. Then, the possibility of potential adverse drug reaction of these contrast media is not fully known and recently, many authors have a growing interest in this point. We have taken 2501 cases of MRI and exccure 1467 cases of Gd-DTPA enhancement scaning(58.7%0 and experienced 12 cases of adverse drug reaction(11 cases: mild reaction. 1 case: severe anaphylactic shock)and the overall incidence of our adverse drug reaction of Gd-DTPA was 0.8%. In conclusion, the adverse drug reaction of Gd-DTPA is not rare and the severe adverse drug reaction of Gd-DTPA may occur. So, the possibility of adverse drug reaction after Gd-DTPA injection should always be kept in mind, especially when the patient has a history of reaction to contrast material, allergy(particularly asthma) and cardiac disease. For the safe use of Gd-DTPA, well trained personnel and nearby emergent care facilities should be available.