Cocaine-derived hippuric acid activates mtDNA-STING signaling in alcoholic liver disease: Implications for alcohol and cocaine co-abuse.

The simultaneous abuse of alcohol-cocaine is known to cause stronger and more unpredictable cellular damage in the liver, heart, and brain. However, the mechanistic crosstalk between cocaine and alcohol in liver injury remains unclear. The findings revealed cocaine-induced liver injury and inflammation in both marmosets and mice. Of note, co-administration of cocaine and ethanol in mice causes more severe liver damage than individual treatment. The metabolomic analysis confirmed that hippuric acid (HA) is the most abundant metabolite in marmoset serum after cocaine consumption and that is formed in primary marmoset hepatocytes. HA, a metabolite of cocaine, increases mitochondrial DNA leakage and subsequently increases the production of proinflammatory factors via STING signaling in Kupffer cells (KCs). In addition, conditioned media of cocaine-treated KC induced hepatocellular necrosis via alcohol-induced TNFR1. Finally, disruption of STING signaling in vivo ameliorated co-administration of alcohol- and cocaine-induced liver damage and inflammation. These findings postulate intervention of HA-STING-TNFR1 axis as a novel strategy for treatment of alcohol- and cocaine-induced excessive liver damage.

A higher probability of subsequent stroke and ischemic heart disease in migraine patients: a longitudinal follow-up study in Korea.

BACKGROUND: Whether migraine is related to the risk of cardiovascular diseases (CVDs) remains unclear. Therefore, we conducted a longitudinal follow-up study to address the association between migraine and the development of CVDs in Korea. METHODS: Using data from the national health screening cohort, we included 45,246 patients diagnosed with migraine between 2002 and 2019 and age-, sex-, income-, and residential region-matched nonmigraine participants at a ratio of 1:4. Participants with previous CVDs were excluded. Cox proportional hazards regression models were used to estimate the hazard ratios of three CVDs, stroke, ischemic heart disease, and heart failure, in patients with migraine after adjusting for potential cardiovascular risk factors. RESULTS: The incidence rate differences of stroke, ischemic heart disease, and heart failure among patients with migraine were 2.61, 1.69, and 0.11, respectively. The probability of developing stroke and ischemic heart disease in patients with migraine was significantly higher than that in controls after controlling for multiple confounders (adjusted hazard ratio [HR] = 1.35, 95% confidence interval [CI] = 1.31-1.39 and adjusted HR = 1.31, 95% CI = 1.26-1.35, respectively). However, when compared with the patients without migraine, patients with migraine did not have an increased HR of developing heart failure (adjusted HR = 1.01, 95% CI = 0.95-1.08). The overall migraine group, as well as groups stratified by migraine subtypes with and without aura, each showed a significantly higher probability of subsequent stroke and ischemic heart disease than the control group. CONCLUSIONS: Our longitudinal follow-up study demonstrated a significant association between the presence of migraine and the development of stroke and ischemic heart disease in Korea, even after adjusting for cardiovascular risk factors.

Miller Fisher syndrome following COVID-19 vaccines: A scoping review.

BACKGROUND AND PURPOSE: Miller Fisher syndrome (MFS), a variant of Guillain-Barré Syndrome (GBS), could be underestimated in evaluations of its adverse events (AEs) following COVID-19 vaccination. We aimed to identify and characterize MFS following COVID-19 vaccination. MATERIALS AND METHODS: Relevant studies reported on during the COVID-19 pandemic were identified in the MEDLINE, Embase, and other databases. RESULTS: Nine cases of MFS following COVID-19 vaccination from various regions were included. Unlike MFS following COVID-19 infection, patients with MFS following COVID-19 vaccination frequently presented with anti-GQ1b antibody positivity (44%, 4/9). Unlike GBS following COVID-19 vaccination, only two of nine (22%) cases of MFS following COVID-19 vaccination had developed after viral-vector-related vaccine administration. CONCLUSIONS: Miller Fisher syndrome following COVID-19 vaccination seems to have a different pathophysiology from MFS following COVID-19 infection and GBS following COVID-19 vaccination. This neurological syndrome with a rare incidence and difficulty in diagnosis should be considered an AE of COVID-19 vaccination.

How Good Are Controlled Attenuation Parameter Scores from Fibroscan to Assess Steatosis, NASH, and Fibrosis?

BACKGROUND AND AIMS: The objective of our study was to determine the concordance rates of steatosis staging by controlled attenuation parameter (CAP) scores from transient elastography (TE) in comparison with liver histology in patients with chronic liver disease and to determine the optimal CAP cutoffs to predict the severity of steatosis and identify those with nonalcoholic steatohepatitis (NASH). METHODS: Patients (n = 217) who had both CAP scores and liver biopsy within a period of 90 days were retrospectively studied. Histology was graded in a blinded fashion by a single pathologist; steatosis was graded on a scale from 0 to 3. Nonalcoholic fatty liver disease activity scores (NAS) scores were calculated for all patients. Optimal CAP cut-points were selected by maximum Youden's index. RESULTS: Area under receiver operating characteristic curve (AUROC) for CAP (using cutoff value ≥ 278 dB/m) in differentiating steatosis 1-3 from 0 was 0.82 (95% CI 0.75-0.89), and 0.79 (95% CI 0.70-0.88) in differentiating steatosis 0-1 from 2 to 3 using CAP cutoff value ≥ 301 dB/m. With CAP cutoff value ≥ 301 dB/m, CAP identified NAS 3 or above with AUROC of 0.82 (95% CI 0.74-0.89). The AUROC for TE in differentiating fibrosis (cutoff 11.9 kPa) 3-4 from 0 to 2 was 0.85 (95% CI 0.77-0.92), and 0.84 (95% CI 0.74-0.93) in differentiating (cutoff 14.4 kPa) 4 from 0 to 3. CONCLUSIONS: Transient elastography is a good modality to accurately diagnose steatosis and NASH and can also differentiate advanced liver fibrosis from early stages.

A Combination of N-Acetylcysteine and Prednisone Has No Benefit Over Prednisone Alone in Severe Alcoholic Hepatitis: A Retrospective Analysis.

INTRODUCTION: In this study, we assessed whether there were any survival advantages with a combination treatment of intravenous N-acetylcysteine (NAC) and prednisone over prednisone alone in those with severe alcoholic hepatitis [discriminant function (DF) ≥ 32]. PATIENTS AND METHODS: Between January 1, 2013, and February 28, 2019, we identified 68 patients (mean age 47.2 years ± 10.1, 57% women, 65% cirrhosis, MELD score 28.1 ± 6.6) with alcoholic hepatitis, and of those, 21 (31%) received prednisone and 47 (69%) received prednisone + NAC. Lille score ≥ 0.45 was considered a poor response. Renal insufficiency was defined as GFR < 60 ml/min/1.73m2 calculated on two separate occasions. RESULTS: DF (74.2 ± 33.6 vs. 56.9 ± 15.9, p = 0.09) was similar, but MELD (29.2 ± 6.3 vs. 25.5 ± 6.4, p = 0.03) scores were higher in the combination group. The overall 30-day and 90-day mortality was 13.2% (9/68) and 20.6% (14/68), respectively. Women were more likely (OR 4.86, 95% CI 1.62-14.59) to respond to treatment based on Lille score compared to men, but the type of treatment regimen had no effect on Lille score (OR 0.84, 95% CI 0.25-2.78). Treatment regimen had no effect on both adjusted and unadjusted survivals. Multivariate analysis, after adjusting for confounding variables, confirmed these observations. DF + renal insufficiency had the highest AUROC (0.86) to predict mortality. CONCLUSION: The combination treatment of NAC + prednisone is not better than prednisone alone in patients with severe alcoholic hepatitis.

Amelioration of Hyperglycemia-Induced Nephropathy by 3,3'-Diindolylmethane in Diabetic Mice.

Type 1 diabetes mellitus (insulin-dependent diabetes) is characterized by hyperglycemia caused by an insulin deficiency. Diabetic nephropathy is a major complication of hyperglycemia. 3,3'-diindolylmethane (DIM)-a natural compound produced from indole-3-carbinol, found in cruciferous vegetables-enhances glucose uptake by increasing the activation of the insulin signaling pathway in 3T3-L1 adipocytes. In this study, we investigated whether DIM could improve insulin-dependent diabetes and nephropathy in streptozotocin (STZ)-induced diabetic mice. In mice, STZ induced hyperglycemia, hunger, thirst, and abnormally increased kidney weight and serum creatinine, which is a renal functional parameter. DIM decreased STZ-increased high blood glucose levels and food and water intake in diabetic mice. DIM also improved diabetic nephropathy by inhibiting the expression of PKC-α, the marker of albuminuria, and TGF-ß1, an indicator of renal hypertrophy, in diabetic mice. Our findings suggest that DIM may ameliorate hyperglycemia and diabetic nephropathy through the inhibition of PKC-α and TGF-ß1 signaling.

Split hand muscle echo intensity index as a reliable imaging marker for differential diagnosis of amyotrophic lateral sclerosis.

OBJECTIVE: The objective of this study was to investigate the usefulness of muscle ultrasound in evaluating dissociated small hand muscle atrophy, termed 'split hand', and its feasibility in the diagnosis of amyotrophic lateral sclerosis (ALS). METHODS: Forty-four patients with ALS, 18 normal subjects and 9 patients with other neuromuscular disorders were included in this study. The hand muscles were divided into three regions, the median-innervated lateral hand muscle group (ML), the ulnar-innervated lateral hand muscle (UL) and the ulnar-innervated medial hand muscle (UM), and the muscle echo intensity (EI) and compound muscle action potential (CMAP) were measured. We calculated the split hand index (SHI) using muscle EI (SHImEI) and CMAP (SHICMAP) for comparison among groups. The SHI was derived by dividing muscle EI (or CMAP) measured at the ML and UL by that measured at the UM. RESULTS: The SHImEI was significantly higher in patients with ALS (51.7±28.3) than in normal controls (29.7±9.9) and disease controls with other neuromuscular disorders (36.5±7.3; P<0.001), particularly in upper limb-onset ALS (66.5±34.0; P<0.001). Receiver operating characteristic curve analysis indicated that the SHImEI had significantly better diagnostic accuracy than the SHICMAP. CONCLUSIONS: The SHImEI was more sensitive in evaluating dissociated small hand muscle atrophy compared with the SHICMAP and may be a reliable diagnostic marker for differentiating ALS from other neuromuscular disorders and healthy controls.

Impact of bacteremia prediction rule in CAP: Before and after study.

OBJECTIVE: In cases of community acquired pneumonia (CAP), it has been known that blood cultures have low yields and rarely affect clinical outcomes. Despite many studies predicting the likelihood of bacteremia in CAP patients, those results have been rarely implemented in clinical practice, and use of blood culture in CAP is still increasing. This study evaluated impact of implementing a previously derived and validated bacteremia prediction rule. METHODS: In this registry-based before and after study, we used piecewise regression analysis to compare the blood culture rate before and after implementation of the prediction rule. We also compared 30-day mortality, emergency department (ED) length of stay, time-interval to initial antibiotics after ED arrival, and any changes to the antibiotics regimen as results of the blood cultures. In subgroup analysis, we compared two groups (with or without the use of the prediction rule) after implementation period, using propensity score matching. RESULTS: Following the implementation, the blood culture rate declined from 85.5% to 78.1% (P=0.003) without significant changes in 30-day mortality and antibiotics regimen. The interval to initial antibiotics (231min vs. 221min, P=0.362) and length of stay (1019min vs. 954min, P=0.354) were not significantly changed. In subgroup analysis, the group that use the prediction rule showed 25min faster antibiotics initiation (P=0.002) and 48min shorter length of stay (P=0.007) than the group that did not use the rule. CONCLUSION: Implementation of the bacteremia prediction rule in CAP patients reduced the blood culture rate without affecting the 30-day mortality and antibiotics regimen.

Incidence and risk factors of delayed intracranial hemorrhage in the emergency department.

OBJECTIVES: This study was performed to identify the risk factors for delayed intracranial hemorrhage and develop a risk stratification system for disposition of head trauma patients with negative initial brain imaging. METHODS: The data source was National Health Insurance Service-National Sample Cohort of Korea. We analyzed adult patients presenting to the ER from January 2004 to September 2012, who underwent brain imaging and discharged with or without short-term observation no longer than two days. The primary outcome was defined as any intracranial bleeding within a month defined by a new appearance of any of the diagnostic codes for intracranial hemorrhage accompanied by a new claim for brain imaging(s) within a month of the index visit. We performed a multivariable logistic regression analysis and built a parsimonious model for variable selection to develop a simple scoring system for risk stratification. RESULTS: During the study period, a total of 19,723 head injury cases were identified from the cohort and a total of 149 cases were identified as having delayed intracranial hemorrhage within 30days. In multivariable logistic regression model, old age, craniofacial fracture, neck injury, diabetes mellitus and hypertension were independent risk factors for delayed intracranial hemorrhage. We constructed the parsimonious model included age, craniofacial fracture and diabetes mellitus. The score showed area under the curve of 0.704 and positive predictive value of the score system was 0.014 when the score≥2. CONCLUSIONS: We found old age, associated craniofacial fracture, any neck injury, diabetes mellitus and hypertension are the independent risk factors of delayed intracranial hemorrhage.

Dodeca-2(E),4(E)-dienoic acid isobutylamide enhances glucose uptake in 3T3-L1 cells via activation of Akt signaling.

Dodeca-2(E),4(E)-dienoic acid isobutylamide (DDI), an alkamide derived from the plant Echinacea purpurea, promotes adipocyte differentiation and activates peroxisome proliferator-activated receptor γ, which is associated with enhanced insulin sensitivity. In the present study, we investigated whether DDI may increase glucose uptake through activation of the insulin signaling pathway in 3T3-L1 adipocytes. DDI increased insulin-stimulated glucose uptake, and expression and translocation of glucose transporter 4 in adipocytes treated with sub-optimal levels of insulin. Additionally, DDI enhanced Akt phosphorylation, whereas phosphoinositide 3-kinase/Akt inhibitors suppressed DDI-induced glucose uptake. These results suggest that DDI may improve insulin sensitivity through the activation of Akt signaling, which leads to enhanced glucose uptake.

Inhibition of Ceramide Decreased the Expression of ATP-Binding Cassette Transporter G5/8 mRNA in an Animal Model of Cholesterol Gallstone.

BACKGROUND: The increased risk of gallstone has been reported in patients with ATP-binding cassette (ABC) transporter polymorphism. The half-transporters ABCG5 and ABCG8 mediate the efflux of cholesterol in hepatocytes and the intestine. We investigated whether ceramide plays a role in cholesterol efflux through the ABC transporters. METHODS: Six-week-old C57BL/6J mice were assigned to 3 groups. The normal group (n = 5) was fed a normal chow diet, the cholesterol group (n = 10) was fed a lithogenic diet, and the myriocin group (n = 15) was fed the lithogenic diet and myriocin, a specific inhibitor of serine-palmitoyl transferase. After 6 weeks, the ABCG5 and ABCG8 transporters were analyzed. RESULTS: The rate of cholesterol gallstone formation in cholesterol group was also higher than that in normal and myriocin groups (0, 70, and 40%, respectively). ABCG5 and ABCG8 mRNA levels were significantly increased in cholesterol group and less increased in myriocin group, relative to that in normal group (p < 0.05). CONCLUSIONS: The inhibition of ceramide biosynthesis by myriocin suppressed gallstone formation and ABCG5/8 mRNA expression. We expect that ceramide's role as a regulator of the ABCG5/8 transporter might be linked to cholesterol gallstone formation.

Enhancement of Glucose Uptake by Meso-Dihydroguaiaretic Acid through GLUT4 Up-Regulation in 3T3-L1 Adipocytes.

Type 2 diabetes is characterized by insulin resistance, which leads to increased blood glucose levels. Adipocytes are involved in the development of insulin resistance, resulting from the dysfunction of the insulin signaling pathway. In this study, we investigated whether meso-dihydroguaiaretic acid (MDGA) may modulate glucose uptake in adipocytes, and examined its mechanism of action. MDGA enhanced adipogenesis through up-regulation of peroxisome proliferator-activated receptor γ and CCAAT/enhancer-binding protein α in 3T3-L1 adipocytes partially differentiated with sub-optimal concentrations of insulin. MDGA also increased glucose uptake by stimulating expression and translocation of glucose transporter 4 (GLUT4) in adipocytes. These results suggest that MDGA may increase GLUT4 expression and its translocation by promoting insulin sensitivity, leading to enhanced glucose uptake.

Anti-cancer effect of N-(3,5-bis(trifluoromethyl)phenyl)-5-chloro-2,3-dihydronaphtho[1,2-b]furan-2-carboxamide, a novel synthetic compound.

Naphthofuran compounds have been known to regulate HNF 4α which is associated with proliferation, progression and metastasis of HCC. In this study, we investigated whether N-(3,5-bis(trifluoromethyl)phenyl)-5-chloro-2,3-dihydronaphtho[1,2-b]furan-2-carboxamide (NHDC), a novel synthetic naphthofuran compound inhibits liver tumor growth through activation of HNF 4α. Treatment with different concentrations (1-10.8 µM) of NHDC for various periods (0-72 h) inhibited liver cancer cells (HepG2, Hep3B) growth as well as colony formation followed by induction of apoptosis in a concentration dependent manner. NHDC also induced expression of the apoptosis regulating genes as well as inhibiting the action of STAT3. These inhibitory effects were associated with enhancement of expression and DNA binding activity of HNF 4α. In vivo study confirmed that liver tumor growth was prevented with NHDC (5 mg/kg), and its effect was also related with inhibition of STAT3 pathway through enhancement of expression and DNA binding activity of HNF 4α. Moreover, siRNA of HNF 4α abolished NHDC-induced cell growth inhibition as well as DNA binding activity and phosphorylation of STAT3. Pull down assay docking prediction analysis proved that NHDC directly binds to hydrophobic fatty acid ligand binding site of HNF 4α. A novel naphthofuran compound, NHDC inhibited liver tumor growth by inactivating of STAT3 through direct biding to HNF 4α.

Interleukin-32γ attenuates ethanol-induced liver injury by the inhibition of cytochrome P450 2E1 expression and inflammatory responses.

Alcohol abuse and alcoholism lead to alcoholic liver disease (ALD), which is a major type of chronic liver disease worldwide. Interleukin-32 (IL-32) is a novel cytokine involved in inflammation and cancer development. However, the role of IL-32 in chronic liver disease has not been reported. In the present paper, we tested the effect of IL-32γ on ethanol-induced liver injury in IL-32γ-overexpressing transgenic mice (IL-32γ mice) after chronic ethanol feeding. Male C57BL/6 and IL-32γ mice (10-12 weeks old) were fed on a Lieber-DeCarli diet containing 6.6% ethanol for 6 weeks. IL-32γ-transfected HepG2 and Huh7 cells, as well as primary hepatocytes from IL-32γ mice, were treated with or without ethanol. The hepatic steatosis and damage induced by ethanol administration were attenuated in IL-32γ mice. Ethanol-induced cytochrome P450 2E1 expression and hydrogen peroxide levels were decreased in the livers of IL-32γ mice, primary hepatocytes from IL-32γ mice and IL-32γ-overexpressing human hepatic cells. The ethanol-induced expression levels of cyclo-oxygenase-2 (COX-2) and IL-6 were reduced in the livers of IL-32γ mice. Because nuclear transcription factor κB (NF-κB) is a key redox transcription factor of inflammatory responses, we examined NF-κB activity. Ethanol-induced NF-κB activities were significantly lower in the livers of IL-32γ mice than in wild-type (WT) mice. Furthermore, reduced infiltration of natural killer cells, cytotoxic T-cells and macrophages in the liver after ethanol administration was observed in IL-32γ mice. These data suggest that IL-32γ prevents ethanol-induced hepatic injury via the inhibition of oxidative damage and inflammatory responses.

IL-32γ enhances TNF-α-induced cell death in colon cancer.

Interleukin (IL)-32 is a recently discovered cytokine that appears to play an important role in human colon cancer growth. We investigated that IL-32γ in combination with TNF-α remarkably inhibited cell growth of human colon cancer cells (HCT116 and SW620) and tumor growth in xenograft-bearing nude mice. The transient enforced overexpression of IL-32γ potentiated the inhibitory effect of TNF-α on DNA synthesis, cell number and protein content, and enhanced apoptosis in colon cancer cells. We also found that knockdown of IL-32γ by siRNA showed the abolishment of cell growth inhibitory effect of TNF-α. The IL-32γ-overexpressing colon cancer cells further increased TNF-α-mediated expression of p38 MAPK as well as that of Bax, cleaved caspase-3 and -9, but decreased that of antiapoptotic proteins such as Bcl-2, cellular inhibitor of apoptosis protein (IAP) and X chromosome IAP. In xenograft model, the lipopolysaccharide (LPS)-injected (1.25 mg/kg) mice inoculated with IL-32γ-transfected HCT116 colon cancer cells were more decrease tumor volume and weight than inoculated with vector. Tumor tissues isolated from LPS-injected mice inoculated with IL-32γ-overexpressing colon cancer cells potentiated the expression levels of pro-apoptotic proteins such as cleaved caspase-3, 9 and Bax, but decreased that of Bcl-2. Furthermore, the mice increased IL-10 production, but decreased IL-6 levels in serum. In conclusion, our results suggest that IL-32γ may potentiate TNF-α-induced cell growth inhibition through activation of p38 MAPK pathways.

Camptothecin inhibits platelet-derived growth factor-BB-induced proliferation of rat aortic vascular smooth muscle cells through inhibition of PI3K/Akt signaling pathway.

The abnormal proliferation of vascular smooth muscle cells (VSMCs) in arterial wall is a major cause of vascular disorders such as atherosclerosis and restenosis after angioplasty. In this study, we investigated not only the inhibitory effects of camptothecin (CPT) on PDGF-BB-induced VSMC proliferation, but also its molecular mechanism of this inhibition. CPT significantly inhibited proliferation with IC50 value of 0.58 µM and the DNA synthesis of PDGF-BB-stimulated VSMCs in a dose-dependent manner (0.5-2 µM ) without any cytotoxicity. CPT induced the cell cycle arrest at G0/G1 phase. Also, CPT decreased the expressions of G0/G1-specific regulatory proteins including cyclin-dependent kinase (CDK)2, cyclin D1 and PCNA in PDGF-BB-stimulated VSMCs. Pre-incubation of VSMCs with CPT significantly inhibited PDGF-BB-induced Akt activation, whereas CPT did not affect PDGF-receptor beta phosphorylation, extracellular signal-regulated kinase (ERK) 1/2 phosphorylation and phospholipase C (PLC)-γ1 phosphorylation in PDGF-BB signaling pathway. Our data showed that CPT pre-treatment inhibited VSMC proliferation, and that the inhibitory effect of CPT was enhanced by LY294002, a PI3K inhibitor, on PDGF-BB-induced VSMC proliferation. In addition, inhibiting the PI3K/Akt pathway by LY294002 significantly enhanced the suppression of PCNA expression and Akt activation by CPT. These results suggest that the anti-proliferative activity of CPT is mediated in part by downregulating the PI3K/Akt signaling pathway.

GT-11 impairs insulin signaling through modulation of sphingolipid metabolism in C2C12 myotubes.

AIMS: Sphingolipids are involved in the regulation of insulin signaling, which is linked to the development of insulin resistance, leading to diabetes mellitus. We aimed to study whether modulation of sphingolipid levels by GT-11 may regulate insulin signaling in C2C12 myotubes. MAIN METHODS: We investigated the effects of sphingolipid metabolism on Akt phosphorylation and glucose uptake using C2C12 myotubes. Either GT-11, an inhibitor of dihydroceramide desaturase 1 and S1P lyase, or siRNA targeting Sgpl1, the gene encoding the enzyme, was employed to determine the effect of sphingolipid metabolism modulation on insulin signaling. Western blotting and glucose uptake assays were used to evaluate the effect of treatments on insulin signaling. Sphingolipid metabolites were analyzed by high performance liquid chromatography (HPLC). KEY FINDINGS: Treatment with GT-11 resulted in decreased Akt phosphorylation and reduced glucose uptake. Silencing the Sgpl1 gene, which encodes S1P lyase, mimicked these findings, suggesting the potential for regulating insulin signaling through S1P lyase modulation. GT-11 modulated sphingolipid metabolism, inducing the accumulation of sphingolipids. Using PF-543 and ARN14974 to inhibit sphingosine kinases and acid ceramidase, respectively, we identified a significant interplay between sphingosine, S1P lyase, and insulin signaling. Treatment with either exogenous sphingosine or palmitic acid inhibited Akt phosphorylation, and reduced S1P lyase activity. SIGNIFICANCE: Our findings highlight the importance of close relationship between sphingolipid metabolism and insulin signaling in C2C12 myotubes, pointing to its potential therapeutic relevance for diabetes mellitus.

Korean Red Ginseng Improves Oxidative Stress-Induced Hepatic Insulin Resistance via Enhancing Mitophagy.

This study explored the potential of saponins from Korean Red Ginseng to target the PINK1/Parkin mitophagy pathway, aiming to enhance insulin sensitivity in hepatocytes-a key factor in metabolic disorders like metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes. Results from both in vitro and in vivo experiments showed increased expression of PINK1 and Parkin, activating mitophagy and reducing oxidative stress through reduction in mitochondrial and total reactive oxygen species. Additionally, improvements in insulin signaling were observed, including the upregulation of phosphorylated IRS and AKT, and downregulation of gluconeogenic enzymes, underscoring the saponins' efficacy in boosting insulin sensitivity. The findings highlighted Korean Red Ginseng-derived saponins as potential treatments for insulin resistance and related metabolic conditions.

Diagnosis, Treatment, and Follow-Up of Giant-Cell Arteritis: A Retrospective Multicenter Study.

BACKGROUND AND PURPOSE: Giant-cell arteritis (GCA) is the most common type of vasculitis in the elderly and is associated with high risks of visual loss and recurrence. Owing to its rarity in Asian populations, the current clinical interventions for these patients are not well known. Here we aimed to characterize the current management status of patients with GCA using Korean multicenter data. METHODS: This retrospective study analyzed medical records of patients with GCA at six Korean university hospitals from February 2009 to November 2022. GCA had originally been diagnosed based on the 1990 American College of Rheumatology (ACR) criteria, and cases were selected for inclusion in this study based on the 2022 ACR/European Alliance of Associations for Rheumatology criteria. We evaluated treatments, follow-up periods, and outcomes (relapse, remission, and adverse drug reactions) in patients with GCA with or without arteritic anterior ischemic optic neuropathy (AAION). RESULTS: This study analyzed 18 patients with a median age of 75.5 years that included 12 females (66.7%). Seven patients (38.8%) had AAION. All patients initially received prednisolone treatment, while four (22.2%) underwent adjuvant treatment with methotrexate and azathioprine during prednisolone tapering. During the median follow-up of 3.5 months (interquartile range: 2.0-23.2 months), 4 patients (22.2%) had prednisolone-related adverse reactions, 2 (11.1%) relapsed, and 13 (72.3%) dropped out. Nine patients (50.0%) experienced remission, with this being sustained in four (36.4%). CONCLUSIONS: This study observed high dropout rates and short follow-ups. Adverse effects of prednisolone were common, and relapses occurred in approximately one-tenth of Korean patients with GCA. Thus, optimizing GCA treatment necessitates regular monitoring and long-term follow-up.