Comparative associations of MASLD and MAFLD with the presence and severity of coronary artery calcification.

We aimed to compare the associations of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated fatty liver disease (MAFLD) with coronary artery calcification (CAC). Patients who simultaneously underwent ultrasonography to diagnose hepatic steatosis and cardiac computed tomography to detect CAC were included. The presence and severity of CAC were defined with CAC-score thresholds of > 0 and > 300, respectively, and patients were divided into the following groups: no MASLD or MAFLD (reference), MASLD-only, MAFLD-only, and overlapping groups. Overall, 1,060/2,773 (38.2%) patients had CAC, of which 196 (18.5%) had severe CAC. The MASLD and MAFLD prevalence rates were 32.6% and 45.2%, respectively, with an overlap of 30.7%. In an ASCVD risk score-adjusted model, both MASLD (adjusted odd ratios [aOR], 1.21; 95% confidence interval [CI], 1.02-1.44; p = 0.033) and MAFLD (aOR 1.20; 95% CI 1.01-1.42, p = 0.034) were associated with CAC, whereas only MASLD (aOR 1.38; 95% CI 1.01-1.89, p = 0.041) was associated with severe CAC. Compared to the reference group, the overlapping group showed an association with CAC (aOR 1.22; 95% CI 1.01-1.47; p = 0.038); however, the MASLD and MAFLD subgroups did not differ in their association with CAC. MASLD may predict a higher risk of ASCVD more effectively than MAFLD.

Visceral Obesity and Its Association with Severe Coronary Artery Calcification in Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease.

Background/Objectives: The role of body composition parameters in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) with presence and severity of coronary artery calcification (CAC) is still not fully elucidated. We aimed to evaluate the impact of computed tomography (CT)-based body composition parameters in patients with MASLD with CAC severity. Methods: In this multicenter study, 1870 individuals underwent cardiac CT for the detection of CAC as well as ultrasonography for the diagnosis of hepatic steatosis. The presence of CAC was defined by a CAC score threshold of >0, while severe CAC was defined by a threshold of >300. Using the abdominal cross-sectional CT images at the L3 vertebra level, we analyzed the skeletal muscle index, visceral to subcutaneous adipose tissue ratio, and muscle density using the Hounsfield unit. Results: Of 648 patients with MASLD, the proportions of presence of CAC and severe CAC were 45.2% and 9.9%, respectively. Visceral obesity was not associated with the presence of CAC after adjustment for age, sex, smoking, statin therapy, type 2 diabetes, and advanced fibrosis (adjusted odds ratio (aOR), 1.38; 95% confidence interval (CI), 0.86-2.23; p = 0.180). However, visceral obesity was independently associated with severe CAC after adjustment for several metabolic risk factors (aOR, 3.54; 95% CI, 1.25-14.90; p = 0.039), and adjustment for atherosclerotic cardiovascular disease risk scores (aOR, 3.74; 95% CI, 1.31-15.79; p = 0.032). Conclusions: Visceral obesity may serve as a novel prognostic CT-based radiological biomarker for patients with MASLD with severe CAC.

Optimization of Electroporation Conditions for Introducing Heterologous DNA into Rhodobacter sphaeroides.

Rhodobacter sphaeroides is a strain capable of both photoautotrophic and chemoautotrophic growth, with various metabolic pathways that make it highly suitable for converting carbon dioxide into high value-added products. However, its low transformation efficiency has posed challenges for genetic and metabolic engineering of this strain. In this study, we aimed to increase the transformation efficiency of R. sphaeroides by deleting the rshI gene coding for an endogenous DNA restriction enzyme that inhibits. We evaluated the effects of growth conditions for making electrocompetent cells and optimized electroporation parameters to be a cuvette width of 0.1 cm, an electric field strength of 30 kV/cm, a resistance of 200 Ω, and a plasmid DNA amount of 0.5 µg, followed by a 24-h recovery period. As a result, we observed over 7,000 transformants per µg of DNA under the optimized electroporation conditions using the R. sphaeroides ΔrshI strain, which is approximately 10 times higher than that of wild-type R. sphaeroides under standard bacterial electroporation conditions. These findings are expected to enhance the application of R. sphaeroides in various industrial fields in the future.

Antimelanogenic and Antioxidant Effects of Postbioics of Lactobacillus Strains in α-MSH-Induced B16F10 Melanoma Cells via CREB/MITF and MAPKs Signaling Pathway.

Abnormal melanin synthesis can lead to severe skin problems. This study investigated the antimelanogenic effects on α-melanocyte stimulating hormone (α-MSH)-induced B16F10 cells using cell-free supernatants of Lactiplantibacillus plantarum WB326 and Levilactobacillus brevis WB2810. Samples were prepared using 1 mg/ml freeze-dried culture supernatant. Cell viability was assessed using B16F10 cells and MTT assay. Tyrosinase inhibition and melanin content decreased in the samples compared to those treated with α-MSH. This effect was also observed when L-DOPA staining was used under a microscope. Moreover, the mRNA expression levels of microphthalmia-associated transcription factor (MITF), tyrosinase, tyrosinase-related protein (TRP)-1, and TRP-2 decreased in the sample-treated group. Protein expression of the CREB/MITF/MAPK signaling pathway was also reduced. Using HPLC analysis, lactic and acetic acids were detected in the culture supernatants. Finally, the antioxidant effects of the samples were confirmed by comparison with those of Trolox and arbutin. According to the experimental results, their utilization is possible in the fields of functional materials and cosmetic ingredients.

High-throughput optimization of organic carbon provision strategies enables enhanced arachidonic acid production in novel microalgae.

BACKGROUND: Microalgae are potential sustainable resources for the production of value-added chemicals that can be used as biofuels, pharmaceuticals, and nutritional supplements. Arachidonic acid (ARA), a omega-6 fatty acid, plays a crucial role in infant development and immune response, and can be used in cosmetics and pharmaceuticals. Demand for industrial-scale ARA production is continuously increasing because of its broad applicability. To address this demand, there has been a significant shift towards microorganism-based ARA production. To accelerate large-scale ARA production, it is crucial to select suitable strains and establish optimal culture conditions. RESULTS: Here, we isolated a novel microalga Lobosphaera incisa CFRC-1, a valuable strain that holds promise as a feedstock for ARA production. Optimal cultivation conditions were investigated using a high-throughput screening method to enhance ARA production in this novel strain. Out of 71 candidates, four organic carbon substrates were identified that could be utilized by L. incisa CFRC-1. Through flask-scale verification, fructose was confirmed as the optimal organic carbon substrate for promoting microalgal growth, total lipid accumulation, and ARA production. Subsequently, we investigated appropriate substrate concentration and cultivation temperature, confirming that the optimal conditions were 30 g L- 1 of fructose and 27 ℃ of temperature. Under these optimized conditions, biomass and ARA production reached 13.05 ± 0.40 g L- 1 and 97.98 ± 7.33 mg L- 1, respectively, representing 9.6-fold and 5.3-fold increases compared to the conditions before optimization conditions. These results achieved the highest biomass and ARA production in flask-scale cultivation, indicating that our approach effectively improved both production titer and productivity. CONCLUSIONS: This study presents a novel microalgae and optimized conditions for enhancing biomass and ARA production, suggesting that this approach is a practical way to accelerate the production of valuable microalgae-based chemicals. These findings provide a basis for large-scale production of ARA-utilizing microalgae for industrial applications.

Temporal trends and long-term outcomes of radiofrequency ablation for hepatocellular carcinoma within the Milan criteria.

No study has analysed the temporal trends of the long-term results and clinical characteristics of patients with hepatocellular carcinoma (HCC) treated using radiofrequency ablation (RFA). Therefore, we examined temporal trends of characteristics of patients and treatment-naïve HCCs within the Milan criteria treated by RFA over 20 years. We retrospectively analysed 1099 patients with HCC within the Milan criteria treated with percutaneous RFA from January 2000 to December 2019. The overall survival (OS), recurrence-free survival (RFS), and factors affecting survival and local tumor progression were analysed using the Kaplan‒Meier method and Cox proportional hazards model. A trend test was performed to analyse the changing trends in participants and treatment outcomes. The overall and RFS of patients improved during the later period. In addition, viral hepatitis-related HCC incidence decreased, whereas that of alcohol- or non-alcoholic fatty liver disease-related HCC increased from the earlier to the later period (P for trend < 0.001). HBV antiviral therapy was increased and improved OS and RFS in patients treated using RFA. The outcomes after RFA over a 20-year period improved due to changes over time in target tumors and patients. The results could be useful for selecting patients who will benefit from RFA.

Endothelial RUNX3 controls LSEC dysfunction and angiocrine LRG1 signaling to prevent liver fibrosis.

BACKGROUND AND AIMS: Liver fibrosis represents a global health burden, given the paucity of approved antifibrotic therapies. Liver sinusoidal endothelial cells (LSECs) play a major gatekeeping role in hepatic homeostasis and liver disease pathophysiology. In early tumorigenesis, runt-related transcription factor 3 (RUNX3) functions as a sentinel; however, its function in liver fibrosis in LSECs remains unclear. This study aimed to investigate the role of RUNX3 as an important regulator of the gatekeeping functions of LSECs and explore novel angiocrine regulators of liver fibrosis. APPROACH AND RESULTS: Mice with endothelial Runx3 deficiency develop gradual and spontaneous liver fibrosis secondary to LSEC dysfunction, thereby more prone to liver injury. Mechanistic studies in human immortalized LSECs and mouse primary LSECs revealed that IL-6/JAK/STAT3 pathway activation was associated with LSEC dysfunction in the absence of RUNX3. Single-cell RNA sequencing and quantitative RT-PCR revealed that leucine-rich alpha-2-glycoprotein 1 ( LRG1 ) was highly expressed in RUNX3-deficient and dysfunctional LSECs. In in vitro and coculture experiments, RUNX3-depleted LSECs secreted LRG1, which activated HSCs throughTGFBR1-SMAD2/3 signaling in a paracrine manner. Furthermore, circulating LRG1 levels were elevated in mouse models of liver fibrosis and in patients with fatty liver and cirrhosis. CONCLUSIONS: RUNX3 deficiency in the endothelium induces LSEC dysfunction, LRG1 secretion, and liver fibrosis progression. Therefore, endothelial RUNX3 is a crucial gatekeeping factor in LSECs, and profibrotic angiocrine LRG1 may be a novel target for combating liver fibrosis.

Effect of direct-acting antivirals on disease burden of hepatitis C virus infection in South Korea in 2007-2021: a nationwide, multicentre, retrospective cohort study.

Background: It is unclear whether direct-acting antivirals (DAAs) treatment improves the disease burden in hepatitis C virus (HCV) infection. This study aimed to investigate the effect of DAA treatment on the reduction of disease burden in patients with HCV infection using individual participant data. Methods: This nationwide multicentre retrospective cohort study recruited patients with HCV infection from 29 tertiary institutions in South Korea. The data collection was done from medical records in each institution. The study included the untreated patients and the DAAs-treated patients and excluded those with a history of interferon-based treatments. Disease burden was the primary outcome, as represented by disability-adjusted life years (DALYs). Improvement in fibrosis after DAA treatment was assessed using APRI, FIB-4 index, and liver stiffness (LS) as assessed by transient elastography. Clinical outcomes were hepatocellular carcinoma (HCC), decompensation, and mortality. Findings: Between January 1, 2007, and February 17, 2022, data from 11,725 patients with HCV infection, 8464 (72%) of whom were treated with DAAs, were analysed. DAA treatment significantly improved APRI- (median 0.64 [interquartile range (IQR), 0.35-1.31]-0.33 [0.23-0.52], p < 0.0001), FIB-4- (median 2.42 [IQR, 1.48-4.40]-1.93 [1.31-2.97], p < 0.0001), and liver LS-based fibrosis (median 7.4 [IQR, 5.3-12.3]-6.2 [4.6-10.2] kPa, p < 0.0001). During the median follow-up period of 27.5 months (IQR, 10.6-52.4), 469 patients died (4.0%), 586 (5.0%) developed HCC, and 580 (4.9%) developed decompensation. The APRI-based DALY estimate was significantly lower in the DAA group than in the untreated group (median 4.55 vs. 5.14 years, p < 0.0001), as was the FIB-4-based DALY estimate (median 5.43 [IQR, 3.00-6.44] vs. 5.79 [3.85-8.07] years, p < 0.0001). The differences between the untreated and DAA groups were greatest in patients aged 40-60 years. In multivariable analyses, the DAA group had a significantly reduced risk of HCC, decompensation, and mortality compared with the untreated group (hazard ratios: 0.41 [95% confidence interval (CI), 0.34-0.48], 0.31 [95% CI, 0.30-0.38], and 0.22 [95% CI, 0.17-0.27], respectively; p < 0.0001). Interpretation: Our findings suggest that DAA treatment is associated with the improvement of liver-related outcomes and a reduction of liver fibrosis-based disease burden in patients with HCV infection. However, further studies using liver biopsy are needed to clarify the effect of DAA treatment on the reduction in the exact fibrosis-based disease burden beyond noninvasive tests. Funding: The Korea Disease Control and Prevention Agency.

Glutamine-derived aspartate is required for eIF5A hypusination-mediated translation of HIF-1α to induce the polarization of tumor-associated macrophages.

Tumor-associated macrophages (TAMs) are vital contributors to the growth, metastasis, and therapeutic resistance of various cancers, including hepatocellular carcinoma (HCC). However, the exact phenotype of TAMs and the mechanisms underlying their modulation for therapeutic purposes have not been determined. Here, we present compelling evidence that glutamine-derived aspartate in TAMs stimulates spermidine production through the polyamine synthesis pathway, thereby increasing the translation efficiency of HIF-1α via eIF5A hypusination. Consequently, augmented translation of HIF-1α drives TAMs to undergo an increase glycolysis and acquire a metabolic phenotype distinct from that of M2 macrophages. Finally, eIF5A levels in tumor stromal lesions were greater than those in nontumor stromal lesions. Additionally, a higher degree of tumor stromal eIF5A hypusination was significantly associated with a more advanced tumor stage. Taken together, these data highlight the potential of inhibiting hypusinated eIF5A by targeting glutamine metabolism in TAMs, thereby opening a promising avenue for the development of novel therapeutic approaches for HCC.

Ascertaining injury risk issues through big data analysis: text-mining based analysis of national emergency response data.

Objectives: Injury prevention can be achieved through various interventions, but it faces challenges due to its comprehensive nature and susceptibility to external environmental factors, making it difficult to detect risk signals. Moreover, the reliance on standardized systems leads to the construction and statistical analysis of numerous injury surveillance data, resulting in significant temporal delays before being utilized in policy formulation. This study was conducted to quickly identify substantive injury risk problems by employing text mining analysis on national emergency response data, which have been underutilized so far. Methods: With emerging issue and topic analyses, commonly used in science and technology, we detected problematic situations and signs by deriving injury keywords and analyzing time-series changes. Results: In total, 65 injury keywords were identified, categorized into hazardous, noteworthy, and diffusion accidents. Semantic network analysis on hazardous accident terms refined the injury risk issues. Conclusion: An increased risk of winter epidemic fractures due to extreme weather, self-harm due to depression (especially drug overdose and self-mutilation), and falls was observed in older adults. Thus, establishing effective injury prevention strategies through inter-ministerial and interagency cooperation is necessary.

Outcome of Atezolizumab Plus Bevacizumab Combination Therapy in High-Risk Patients with Advanced Hepatocellular Carcinoma.

Real-world data regarding treatment with atezolizumab plus bevacizumab in high-risk patients with advanced HCC are lacking. In this multicenter retrospective cohort study, a total of 215 patients with advanced HCC received atezolizumab plus bevacizumab treatment at four tertiary hospitals. High-risk patients were those with grade Vp4 portal vein thrombus, bile duct invasion, or more than 50% liver infiltration. In total, 98 (45.6%) were the high-risk population, 186 (86.5%) were considered to be Child-Pugh class A, and 128 (59.5%) had previously received neoadjuvant or concomitant radiation treatment. Median overall survival (OS) was 11.25 months (95% CI, 9.50-13.10), and the median progression-free survival (PFS) was 8.00 months (95% CI, 6.82-9.18). In the high-risk population, the median OS was 10 months (95% CI, 8.19-11.82) and the median PFS was 6.50 months (95% CI, 3.93-9.08). In the high-risk population, multivariate analysis indicated that radiation therapy and lower ALBI grade were associated with better OS and PFS. A total of 177 (82.3%) patients experienced adverse events of any grade, the most common being proteinuria (23.7%). Atezolizumab plus bevacizumab treatment showed consistent efficacy and tolerability in both the total and high-risk population. Radiation therapy combined with atezolizumab plus bevacizumab treatment might be helpful to improve PFS and OS in high-risk populations.

The Clinical Significance of Myosteatosis in Survival Outcomes in Patients with Hepatocellular Carcinoma Treated with Sorafenib.

The role of body composition parameters in sorafenib-treated hepatocellular carcinoma (HCC) patients is still not fully elucidated. Here, we aimed to evaluate the impact of computed tomography (CT)-based body composition parameters on the survival of such patients. In this multicenter study, we analyzed the data of 245 sorafenib-treated HCC patients from January 2008 to December 2019. Sarcopenia, visceral obesity, and myosteatosis were defined by using cross-sectional CT images at the third lumbar vertebra level. The effects of these parameters on overall survival (OS) and progression-free survival (PFS) were evaluated. The median age was 67.0 years (interquartile range: 61.0-78.0 year), and 211 patients (86.1%) were male. The median OS and PFS were 7.9 months and 4.8 months, respectively. Vascular invasion (hazard ratio (HR), 1.727; 95% confidence interval (CI), 1.258-2.371; p = 0.001), extrahepatic metastasis (HR, 1.401; 95% CI, 1.028-1.908; p = 0.033), alpha-fetoprotein level > 200 ng/mL (HR, 1.559; 95% CI, 1.105-2.201; p = 0.012), and myosteatosis (HR, 1.814; 95% CI, 1.112-2.960; p = 0.017) were associated with OS. Patient mortality was significantly higher in the group with two or more risk factors than in the group with fewer risk factors. In conclusion, myosteatosis may be a novel prognostic CT-based radiological biomarker in sorafenib-treated HCC patients.

Abdominal CT Segmentation for Body Composition Assessment Using Network Consistency Learning.

Estimating skeletal muscle (SM) and adipose tissues is an invaluable prognostic indicator in cancer treatment, major surgeries, and general health screening. Body composition is usually measured with abdominal computed tomography (CT) scans acquired in clinical settings. The whole-body SM volume is correlated with the estimated SM based on the measurement of a single two-dimensional vertebral slice. It is necessary to label a CT image at the pixel level to estimate SM, known as semantic segmentation. In this work, we trained a segmentation model using the labeled abdominal CT slices and the additional unlabeled slices. In particular, we trained two identical segmentation networks with differently initialized weights. Network Consistency Learning (NCL) allowed learning from unlabeled images by forcing the predictions from both networks to be the same. We segmented abdominal CT images from a newly created in-house dataset. The proposed approach gained 10% better performance in terms of Dice similarity score (DSC) than that obtained by a standard supervised network demonstrating the effectiveness of NCL in exploiting unlabeled images.Clinical relevance- An efficient and cost-effective method is proposed for assessing body composition from limited labeled and abundant unlabeled CT images to facilitate fast diagnosis, prognosis, and interventions.

Cell Nuclei Segmentation With Dynamic Token-Based Attention Network.

Cell nuclei segmentation is crucial for analyzing cell structure in different tasks, i.e., cell identification, classification, etc., to treat various diseases. Several convolutional neural network-based architectures have been proposed for segmenting cell nuclei. Although these methods show superior performance, they lack the ability to predict reliable masks when using biomedical image data. This paper proposes a novel Dynamic Token-based Attention Network (DTA-Net). Combining convolutional neural networks (CNN) with a vision transformer (ViT) allows us to capture detailed spatial information from images efficiently by encoding local and global features. Dynamic Token-based Attention (DTA) module calculates attention maps keeping the overall computational and training costs minimal. For the nuclei segmentation task on the 2018 Science Bowl dataset, our proposed method outperformed SOTA networks with the highest Dice similarity score (DSC) of 93.02% and Intersection over Union (IoU) of 87.91% without using image pre- or post-processing techniques. The results showed that high-quality segmentation masks could be obtained by configuring a ViT in the most straight forward manner.Clinical relevance- In this work, the segmentation of cell nuclei in microscopy images is carried out automatically, irrespective of their appearance, density, magnification, illumination, and modality.

Tissue Circular RNA_0004018 and 0003570 as Novel Prognostic Biomarkers for Hepatitis B-Related Hepatocellular Carcinoma.

The clinical significance of hsa_circ_0004018 and hsa_circ_0003570 in patients with hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) is unclear. We aimed to explore the clinical significance and prognostic utility of these two circular RNAs (circRNAs) in patients with HBV-HCC. Based on 86 paired tissue samples of HCC and adjacent non-HCC, the relative expression profiles of hsa_circ_0004018 and hsa_circ_0003570 were determined using quantitative real-time polymerase chain reactions. The cut-off values were the median expression of each of the two circRNAs in 86 patients with HBV-HCC. The combination group comprised patients with high levels of the two circRNAs. Clinicopathological features, body composition profiles at the L3 level, and survival rates were investigated. The expression of hsa_circ_0004018 and hsa_circ_0003570 was downregulated in HCC tissues compared with non-HCC tissues. High expression levels of hsa_circ_0003570 (hazard ratio (HR), 0.437; p = 0.009) and hsa_circ_0004018 (HR, 0.435; p = 0.005) were inversely independent risk factors for overall and progression-free survival in patients with HBV-HCC, whereas the combination group was also an inversely independent risk factor for overall (HR, 0.399; p = 0.005) and progression-free survival (HR, 0.422; p = 0.003) in patients with HBV-HCC. The combination of hsa_circ_0003570 and hsa_circ_0004018 may be a potential prognostic biomarker for HBV-HCC.

A multidisciplinary approach with immunotherapies for advanced hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a highly aggressive disease that is usually diagnosed at an advanced stage. Advanced HCC has limited treatment options and often has a poor prognosis. For the past decade, tyrosine kinase inhibitors have been the only treatments approved for advanced HCC that have shown overall survival (OS) benefits; however, but their clinical efficacy has been limited. Recent trials have demonstrated promising advancements in survival outcomes through immunotherapy-based treatments, such as combinations of immune checkpoint inhibitors (ICIs) with other ICIs, antiangiogenic drugs, and locoregional therapies. The atezolizumab-bevacizumab and durvalumab-tremelimumab (STRIDE) regimen has significantly improved survival rates as a first-line treatment and has become the new standard of care. Therefore, combined treatments for advanced HCC can result in better treatment outcomes owing to their synergistic effects, which requires a multidisciplinary approach. Ongoing studies are examining other therapeutic innovations that can improve disease control and OS rates. Despite improvements in the treatment of advanced HCC, further studies on the optimal treatment selection and sequences, biomarker identification, combination approaches with other therapies, and development of novel immunotherapy agents are required. This review presents the current treatment options and clinical data of the ICI-based combination immunotherapies for advanced HCC from a multidisciplinary perspective.

Impact of metabolic factors on risk of cardiovascular disease in nondiabetic metabolic dysfunction-associated fatty liver disease.

BACKGROUND AND AIM: Changing terminology of non-alcoholic fatty liver disease (NAFLD) to metabolic dysfunction-associated fatty liver disease (MAFLD) is recently proposed by expert panels based on metabolic dysregulations. However, clinical evidences for the risk of cardiovascular disease (CVD) in MAFLD are limited. The aim of this study is evaluating the association of cardiovascular risk in these two terminology and subgroups of MAFLD. METHODS: A total of 2133 individuals who underwent ultrasound and cardiac computed tomography contemporaneously were included at a single medical checkup center. Ultrasound was used to define fatty liver, and coronary artery calcification (CAC) defined a coronary artery calcium score above 0 was used to estimate the cardiovascular risk. RESULTS: Overall, 911 participants were diagnosed with fatty liver. In the unadjusted analysis, NAFLD (OR = 1.4, 95% confidence interval [CI] = 1.05-1.85, p = 0.019) and MAFLD (OR = 1.55, 95% CI = 1.29-1.86, p = 0.046) were significantly associated with CAC. However, in sex and age-adjusted analyses, only MAFLD was associated with CAC (adjusted OR [aOR] = 1.38, 95% CI = 1.14-1.69, p = 0.001). Of the three subgroups of MAFLD (diabetic, nondiabetic overweight/obese, and nondiabetic normal weight/lean with at least two metabolic abnormalities), only diabetic MAFLD was associated with CAC (aOR = 2.65, 95% CI = 1.98-3.55, p < 0.001). When the minimal number of metabolic risk abnormalities increased to three, nondiabetic normal-weight/lean MAFLD was associated with CAC (aOR = 1.35, 95% CI = 1.02-1.77, p = 0.034). CONCLUSION: Diabetic MAFLD predicted high-risk CVD phenotypes the best. Metabolic risk abnormalities in nondiabetic MAFLD patients were independently associated with the risk of CVD. The proposed diagnostic criteria for nondiabetic MAFLD need further investigation in terms of CVD risk.

Plasma cell myeloma initially diagnosed as light-chain deposition disease on liver biopsy: A case report and literature review.

RATIONALE: Light-chain deposition disease (LCDD) is a rare condition characterized by the abnormal deposition of monoclonal light chains (LCs) in multiple organs, leading to progressive organ dysfunction. Herein, we report a case of plasma cell myeloma initially diagnosed as LCDD on liver biopsy performed for prominent cholestatic hepatitis. PATIENT CONCERNS: A 55-year-old Korean man complained of dyspepsia as the main symptom. On abdominal computed tomography performed at another hospital, the liver showed mildly decreased and heterogeneous attenuation with mild periportal edema. Preliminary liver function tests revealed abnormal results. The patient was treated for an unspecified liver disease; however, his jaundice gradually worsened, prompting him to visit our outpatient hepatology clinic for further evaluation. Magnetic resonance cholangiography revealed liver cirrhosis with severe hepatomegaly of unknown cause. A liver biopsy was performed for the diagnosis. Hematoxylin and eosin staining revealed diffuse extracellular amorphous deposits in perisinusoidal spaces with compressed hepatocytes. The deposits, which morphologically resembled amyloids, were not stained by Congo red but stained strongly positive for kappa LCs and weakly positive for lambda LCs. DIAGNOSES: Therefore, the patient was diagnosed with LCDD. Further systemic examination revealed a plasma cell myeloma. INTERVENTIONS: Fluorescence in situ hybridization, cytogenetics, and next-generation sequencing tested in bone marrow showed no abnormalities. The patient initially received bortezomib/lenalidomide/dexamethasone as the treatment regimen for plasma cell myeloma. OUTCOMES: However, he died shortly thereafter because of coronavirus disease 2019 complications. LESSONS: This case demonstrates that LCDD may present with sudden cholestatic hepatitis and hepatomegaly, and may be fatal if patients do not receive appropriate and timely treatment because of delayed diagnosis. Liver biopsy is useful for the diagnosis of patients with liver disease of unknown etiology.

Neuroprotective effects of fermented tea in MPTP-induced Parkinson's disease mouse model via MAPK signaling-mediated regulation of inflammation and antioxidant activity.

Parkinson's disease (PD) is a neurodegenerative disorder that is characterized by dopaminergic neuronal damage. In this study, three tea extracts from Hadong, Korea, were evaluated in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity damage model (C57BL/6 mice) for their therapeutic effects against PD: green tea (GT), semi-fermented tea (SFT), and fermented tea (FT). Theaflavin content in the teas increased but catechin content decreased with the degree of fermentation. In addition, SFT showed the highest theanine and γ-aminobutyric acid contents. SFT at a concentration of 25 µg/mL showed the highest activity in the 2,2-diphenyl-1-picrylhydrazyl radical scavenging assay among all samples. Furthermore, the 2,2'-azino-bis 3-ethylbenzothiazoline-6-sulfonic acid radical scavenging activity of 25 µg/mL SFT was higher than that of l-ascorbic acid. Fermented tea suppressed the expression of inflammatory cytokines, such as interleukin-6, tumor necrosis factor-alpha, inducible nitric oxide synthase, cyclooxygenase-2, and macrophage-1, as well as inhibited overexpression of apoptotic signals, including p-53, cleaved caspase-3, and poly (ADP-ribose) polymerase-1. Moreover, GT, SFT, and FT regulated the MPTP-induced oxidative stress-related factors, including superoxide dismutase, glutathione-S-transferase, and nicotinamide adenine dinucleotide phosphate oxidase 4. Fermented tea also alleviated MPTP-induced behavioral impairment and dopaminergic neuronal damage and reduced α-synuclein levels. These results indicate that fermented tea is effective for the treatment of neuro-inflammatory, neuro-apoptotic, and neuro-oxidative disorders.