Background/Aims: Chronic hepatitis C (CHC) patients who failed antiviral therapy are at increased risk for hepatocellular carcinoma (HCC). This study assessed the potential role of metformin and statins, medications for diabetes mellitus (DM) and hyperlipidemia (HLP), in reducing HCC risk among these patients. Methods: We included CHC patients from the T-COACH study who failed antiviral therapy. We tracked the onset of HCC 1.5 years post-therapy by linking to Taiwan’s cancer registry data from 2003 to 2019. We accounted for death and liver transplantation as competing risks and employed Gray’s cumulative incidence and Cox subdistribution hazards models to analyze HCC development. Results: Out of 2,779 patients, 480 (17.3%) developed HCC post-therapy. DM patients not using metformin had a 51% increased risk of HCC compared to non-DM patients, while HLP patients on statins had a 50% reduced risk compared to those without HLP. The 5-year HCC incidence was significantly higher for metformin non-users (16.5%) versus non-DM patients (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Statin use in HLP patients correlated with a lower HCC risk (3.8%) compared to non-HLP patients (12.5%; aSHR=0.50; P<0.001). Notably, the increased HCC risk associated with non-use of metformin was primarily seen in non-cirrhotic patients, whereas statins decreased HCC risk in both cirrhotic and non-cirrhotic patients. Conclusions Metformin and statins may have a chemopreventive effect against HCC in CHC patients who failed antiviral therapy. These results support the need for personalized preventive strategies in managing HCC risk.

Background/Aims: Galectin-3 plays a key pathogenic role in cardiac hypertrophy and heart failure. The present study aimed to investigate the effects of galectin-3 on cardiomyopathy – related factors and cardiac contractility in a rat model of cirrhotic cardiomyopathy. Methods: Rats were divided into two sets, one for a functional study, the other for cardiac contractile-related protein evaluation. There were four groups in each set: sham operated and sham plus N-acetyllactosamine (N-Lac, a galectin-3 inhibitor; 5 mg/kg); bile duct ligated (BDL) and BDL plus N-Lac. Four weeks after surgery, ventricular level of galectin-3, collagen I and III ratio, tumor necrosis factor alpha (TNFα), and brain natriuretic peptide (BNP) were measured either by Western blots or immunohistochemistry or enzyme-linked immunosorbent assay. Blood pressure was measured by polygraph recorder. Cardiomyocyte contractility was measured by inverted microscopy. Results: Galectin-3 and collagen I/III ratio were significantly increased in cirrhotic hearts. TNFα and BNP were significantly increased in BDL serum and heart compared with sham controls. Galectin-3 inhibitor significantly decreased galectin-3, TNFα, and BNP in cirrhotic hearts but not in sham controls. N-Lac also significantly improved the blood pressure, and systolic and diastolic cardiomyocyte contractility in cirrhotic rats but had no effect on sham controls. Conclusion Increased galectin-3 in the cirrhotic heart significantly inhibited contractility via TNFα. Inhibition of galectin-3 decreased the cardiac content of TNFα and BNP and reversed the decreased blood pressure and depressed contractility in the cirrhotic heart. Galectin-3 appears to play a pathogenic role in cirrhotic cardiomyopathy.

Ectopic pancreas is defined as an abnormally located pancreatic tissue not sufficiently connected with the normal pancreas, which rarely occurs in neonates. To our knowledge, only a few cases of ectopic pancreas have been reported in newborns in South Korea. We report a case of ectopic pancreas as the cause of intussusception and jejunal atresia in a newborn. This clinical association is extremely rare, and this is the first report in South Korea.

Ectopic pancreas is defined as an abnormally located pancreatic tissue not sufficiently connected with the normal pancreas, which rarely occurs in neonates. To our knowledge, only a few cases of ectopic pancreas have been reported in newborns in South Korea. We report a case of ectopic pancreas as the cause of intussusception and jejunal atresia in a newborn. This clinical association is extremely rare, and this is the first report in South Korea.

Chronic traumatic encephalopathy (CTE) is a distinct neurodegenerative disease that associated with repetitive head trauma. CTE is neuropathologically defined by the perivascular accumulation of abnormally phosphorylated tau protein in the depths of the sulci in the cerebral cortices. In advanced CTE, hyperphosphorylated tau protein deposits are found in widespread regions of brain, however the mechanisms of the progressive neurodegeneration in CTE are not fully understood. In order to identify which proteomic signatures are associated with CTE, we prepared RIPA-soluble fractions and performed quantitative proteomic analysis of postmortem brain tissue from individuals neuropathologically diagnosed with CTE. We found that axonal guidance signaling pathwayrelated proteins were most significantly decreased in CTE. Immunohistochemistry and Western blot analysis showed that axonal signaling pathway-related proteins were down regulated in neurons and oligodendrocytes and neuron-specific cytoskeletal proteins such as TUBB3 and CFL1 were reduced in the neuropils and cell body in CTE. Moreover, oligodendrocyte-specific proteins such as MAG and TUBB4 were decreased in the neuropils in both gray matter and white matter in CTE, which correlated with the degree of axonal injury and degeneration. Our findings indicate that deregulation of axonal guidance proteins in neurons and oligodendrocytes is associated with the neuropathology in CTE. Together, altered axonal guidance proteins may be potential pathological markers for CTE.
Axons ; Blotting, Western ; Brain Injury, Chronic ; Brain ; Cell Body ; Cerebral Cortex ; Craniocerebral Trauma ; Cytoskeletal Proteins ; Gray Matter ; Humans ; Immunohistochemistry ; Neurodegenerative Diseases ; Neurons ; Neuropathology ; Neuropil ; Oligodendroglia ; tau Proteins ; White Matter

INTRODUCTIONBreast reconstruction is an integral part of breast cancer management with the aim of restoring a breast to its natural form. There is increasing awareness among women that it is a safe procedure and its benefits extend beyond aesthetics. Our aim was to establish the rate of breast reconstruction and provide an overview of the patients who underwent breast reconstruction at National University Hospital (NUH), Singapore.

METHODSWe evaluated factors that impact a patient's decision to proceed with breast reconstruction, such as ethnicity, age, time and type of implant. We retrospectively reviewed the medical records of women who had breast cancer and underwent breast surgery at NUH between 2001 and 2010.

RESULTSThe breast reconstruction rate in this study was 24.3%. There were 241 patients who underwent breast reconstruction surgeries (including delayed and immediate procedures) among 993 patients for whom mastectomies were done for breast cancer. Chinese patients were the largest ethnic group who underwent breast reconstruction after mastectomy (74.3%). Within a single ethnic patient group, Malay women had the largest proportion of women undergoing breast reconstruction (60.0%). The youngest woman in whom cancer was detected in our study was aged 20 years. Malay women showed the greatest preference for autologous tissue breast reconstruction (92.3%). The median age at cancer diagnosis of our cohort was 46 years.

CONCLUSIONWe noted increases in the age of patients undergoing breast reconstruction and the proportion of breast reconstruction cases over the ten-year study period.

No abstract available.
Breast* ; Fasciitis, Necrotizing* ; Transplants*

Fucodiphlorethol G (6'-[2,4-dihydroxy-6-(2,4,6-trihydroxyphenoxy)phenoxy]biphenyl-2,2',4,4',6-pentol) is a compound purified from Ecklonia cava, a brown alga that is widely distributed offshore of Jeju Island. This study investigated the protective effects of fucodiphlorethol G against oxidative damage-mediated apoptosis induced by ultraviolet B (UVB) irradiation. Fucodiphlorethol G attenuated the generation of 2, 2-diphenyl-1-picrylhydrazyl radicals and intracellular reactive oxygen species in response to UVB irradiation. Fucodiphlorethol G suppressed the inhibition of human keratinocyte growth by UVB irradiation. Additionally, the wavelength of light absorbed by fucodiphlorethol G was close to the UVB spectrum. Fucodiphlorethol G reduced UVB radiation-induced 8-isoprostane generation and DNA fragmentation in human keratinocytes. Moreover, fucodiphlorethol G reduced UVB radiation-induced loss of mitochondrial membrane potential, generation of apoptotic cells, and active caspase-9 expression. Taken together, fucodiphlorethol G protected human keratinocytes against UVB radiation-induced cell damage and apoptosis by absorbing UVB radiation and scavenging reactive oxygen species.
Apoptosis ; Caspase 9 ; DNA Fragmentation ; Humans ; Keratinocytes ; Membrane Potential, Mitochondrial ; Oxidative Stress* ; Reactive Oxygen Species

BACKGROUND: Urinary trypsin inhibitor (UTI), which is speculated to have anti-inflammatory effects, is one of serine protease inhibitors found in human urine and blood. The present study was conducted to clarify the effect of urinary trypsin inhibitor (UTI) on human neutrophil activation and its intracellular signaling mechanism in vitro. METHODS: To assess the possible interactions between UTI and lipopolysaccharide (LPS) in neutrophil activation, neutrophils from human blood were incubated with varying concentrations of UTI (1, 10, 100, 1,000 and 10,000 U/ml) plus LPS (100 ng/ml) or LPS alone in 24-well plates (5 x 106 cells/well). We measured protein levels for interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-alpha) using enzyme-linked immunosorbent assay (ELISA) kits after 4 hours of incubation period. To elucidate the intracellular signaling pathway, we also measured the levels of phosphorylation of p38, ERK1/2 and JNK via Western blot analysis. Moreover, the nuclear levels of nuclear factor-kappa B (NF-kappaB) were determined with electrophoretic mobility shift assays (EMSA). RESULTS: UTI decreased the expression of inflammatory cytokines, including TNF-alpha and IL-6, and activation of intracellular signaling pathways, such as JNK, but not P38, ERK1/2 and nuclear translocation of NF-kappaB. CONCLUSIONS: UTI can attenuate LPS-induced neutrophil responses and may partially contribute to the treatment of neutrophil-mediated inflammatory diseases.
Blotting, Western ; Cytokines ; Electrophoretic Mobility Shift Assay ; Enzyme-Linked Immunosorbent Assay ; Glycoproteins ; Humans ; Interleukin-6 ; Interleukins ; Mitogen-Activated Protein Kinases ; Neutrophil Activation ; Neutrophils ; Phosphorylation ; Serine Proteinase Inhibitors ; Trypsin ; Tumor Necrosis Factor-alpha