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The main goal of total disc replacement (TDR) is to preserve motion. Despite reports of good clinical outcomes, various degrees of heterotopic ossification after TDR have been reported. The purpose of this study was to investigate the prevalence and its clinical relevance of heterotopic ossification. We evaluated 65 consecutive patients (82 segments) with mean follow-up duration of 45 months (range, 12-88 months). Two kinds of prosthesis, ProDisc® for 75 segments (91.5%) and CHARITE™ for seven segments (8.5%), were used. Patients with heterotopic ossification were compared with those without heterotopic ossification with regard to segmental flexion-extension ROM, VAS and ODI. We analysed the occurrence site by nine zones. Heterotopic ossification was detected in 25 out of 82 segments (30.5%) at a mean follow-up of 17 months. According to McAfee's classification, there was Class-I heterotopic ossification in eight segments (9.8%), Class-II in 12 segments (14.6%), and Class-III in five segments (6.1%). There was no Class-IV heterotopic ossification. There were no significant differences in the segmental ROM, VAS and ODI between the patients with Class-I or Class-II heterotopic ossification and those without heterotopic ossification The segmental ROM in the patients with Class-III heterotopic ossification was significantly decreased compared with the patients without heterotopic ossification (p = 0.018). But VAS and ODI were not significantly different compared with those of patients with no heterotopic ossification. Most heterotopic ossification (82.5%) was detected in the anterior and posterior aspects. In conclusion, most of the heterotopic ossification (Classes I and II) did not affect segmental ROM and clinical outcomes such as pain or function. In Class-III heterotopic ossification segmental ROM was decreased, but it did not affect clinical outcomes. [ABSTRACT FROM AUTHOR]

The objective of this study was to determine the effects of green tea extract (GTE) on lipid metabolism in obese animal models. Male C57BL/6J-Lep ob/ob mice were divided into control and GTE (0.05 g/100 g diet) groups, which were fed a high-fat (20 g/100 g diet) diet for 12 weeks. Supplementation of GTE significantly reduced (p < 0.01) perirenal and total white adipose tissue weights compared with the control group. Also, the plasma HDL-cholesterol level was significantly higher in the GTE group than in the control group, therefore the GTE group showed a higher HDL-cholesterol/total-cholesterol ratio (HTR) and lower atherogenic index (AI) level than the control group. A reduction of hepatic triglyceride content and adipose tissue weight in the GTE group was related to the suppression of enzyme activities for fatty acid synthesis (glucose-6-phosphate dehydrogenase and malic enzyme) without affecting fatty acid oxidation enzyme (beta-oxidation and carnitine palmitoyl transferase) activities in hepatic and adipose tissue. The current results showed that supplementation of green tea extract is beneficial for antiobesity by the suppression of lipogenesis via regulation of related enzyme activities in hepatic and adipose tissue. [ABSTRACT FROM AUTHOR]

Background: Leukoaraiosis is a term used to define the abnormal appearance of subcortical white matter of the brain by means of neuroimaging and is regarded as an intermediate surrogate of stroke. The goal of this study is to identify the prevalence of leukoaraiosis and analyze predictors of risk of leukoaraiosis. Study Design: Cross-sectional study. Setting& Participants: 57 peritoneal dialysis (PD) patients without diabetes treated in 3 academic medical-associated dialysis units who did not have a history of cerebrovascular disease or neurological symptoms compared with a convenience sample of 57 age- and sex-matched hypertensive control subjects with normal renal function. Predictor: End-stage renal disease treated by PD compared with hypertension, adjusted for clinical and laboratory characteristics. Outcome& Measurement: Hyperintense areas on magnetic resonance imaging T2 high-signal intensity scoring system. Results: The prevalence of leukoaraiosis was significantly greater in patients on PD therapy than controls (68.4% versus 17.5%; P < 0.001). High T2 signal intensity score in patients on PD therapy compared with controls was significantly higher in the anterior circulation of the brain, relatively sparing the posterior fossa. End-stage renal disease, age, and poor control of blood pressure were significant independent predictors of leukoaraiosis. Limitations: There is the possibility that biases regarding the selection of enrolled patients had an influence on a study result. Conclusions: Cerebral magnetic resonance imaging of PD patients without evidence of cerebrovascular disease showed a high prevalence of leukoaraiosis in the anterior circulation of the brain. Old age, poorly controlled hypertension, and the PD procedure itself and/or end-stage renal disease seem to be associated with the presence of leukoaraiosis. [ABSTRACT FROM AUTHOR]

Adoptive cell therapy (ACT) is a type of immunotherapy in which autologous or allogeneic immune cells, such as tumor-infiltrating lymphocytes or engineered lymphocytes, are infused into patients with cancer to eliminate malignant cells. Recently, autologous T cells modified to express a chimeric antigen receptor (CAR) targeting CD19 showed a positive response in clinical studies for hematologic malignancies and have begun to be used in clinical practice. This article discusses the current status and promise of ACT research in hepatocellular carcinoma (HCC), focusing on challenges in off-the-shelf ACT using primary cells or induced pluripotent stem cells (iPSCs) with or without genetic engineering. Early clinical trials of autologous GPC-3-, MUC1-, or CEA-targeted CAR-T cell therapies are underway for HCC. There is a growing demand for the development of off-the-shelf therapies due to the high cost and manufacturing issues associated with autologous CAR-T. The development of ACT from various cell sources, such as NK cells, NKT cells, macrophages, and γδ T cells without MHC restriction other than T cells has been proposed. Advances in genome editing, including HLA gene knockout to avoid GvHD, and strategies to enhance efficacy in overcoming the suppressive tumor microenvironment, are used to create universal 'off-the-shelf' CAR-T cells which can be used immediately as therapeutic products from healthy donors or iPSC-derived immune cells. Despite several limitations, cell-based immunotherapy is expected to become a key cancer treatment modality for both hematologic malignancies and solid tumors including HCC, thanks to technological advancements overcoming these challenges., (© 2025 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Patients undergoing endoscopic submucosal dissection under monitored anesthesia care (MAC) with remimazolam may develop respiratory distress during the procedure. In these cases, low doses of flumazenil improved respiratory distress without completely reversing sedation, which is a novel phenomenon. This study aimed to explore the ED90 of flumazenil to selectively improve respiratory distress in patients with MAC treated with remimazolam., Methods: Flumazenil dose determination followed a biased-coin up-and-down design. Starting with a dose of 5 mcg, if respiratory distress improved, the biased-coin method was used to give the same dose in the next patient with a probability of 8/9, and a decreased dose of 5 mcg in the next patient with a probability of 1/9. Any improvement in respiratory distress within 30 s of flumazenil administration was recorded. After the procedure, patients were asked whether they had any memory recall during the procedure. Centered isotonic regression was used to determine the ED90 of flumazenil., Results: Sixty patients were included in the study. The estimated ED90 was 76.72 mcg (95% CI: 68.07-102.62). Memory recall occurred in two of thirteen patients (15%) near the ED90 dose range (75 mcg and 80 mcg). None of the patients developed major postoperative complications (bleeding, perforation, or aspiration) within the 2-day postoperative period., Conclusions: This study determined that the ED90 of flumazenil for effectively alleviating respiratory distress in patients undergoing MAC with remimazolam was 76.7 mcg, without reversing consciousness. These findings provide valuable guidance for the care of patients undergoing sedation.

Background: Although clinicians frequently encounter incidentally detected gastroduodenal extrinsic compressive lesions (GDECLs) on upper gastrointestinal endoscopy (UGE), the optimal management approach for GDECLs has not been fully established. This study aimed to stratify and identify important factors associated with clinically significant GDECLs that require regular follow-up or further treatment., Methods: Between June 2007 and December 2015, a total of 73 patients with suspected GDECLs on UGE at Kyung Hee University Hospital at Gangdong were identified and studied retrospectively. After the final diagnosis, patients were divided into the following two groups: clinically significant GDECLs, which requires regular follow-up or further treatment, and clinically non-significant GDECLs., Results: Among 73 GDECLs, 23 (31.5%) lesions were classified as clinically significant GDECLs and 50 (68.5%) as clinically non-significant GDECLs. In multivariate analysis, clinical and endoscopic parameters that were independently associated with clinically significant GDECLs included older age (≥ 60 years), large size (≥ 4 cm) of extrinsic compression, previous history of intra-abdominal malignancy, and symptoms of abdominal distension (all p < 0.05)., Conclusions: Several clinical and endoscopic parameters showed significant association with the identification of clinically significant GDECLs on endoscopy. These predictive factors might be useful in determining whether to perform further diagnostic work-up in patients with GDECLs., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The anti-obesity effects of Lactobacillus paragasseri (L. paragasseri) have been reported, but the exact mechanisms have not been elucidated. There are also no reports on the impact of L. paragasseri on the gut microbiota environment. Recently, the incidence of sarcopenia due to obesity has increased regardless of age, exacerbating metabolic disorders caused by obesity. Therefore, we investigate the beneficial effects of L. paragasseri SBT2055 (LG2055) on obesity along with obese sarcopenia and gut microbiome changes. C57BL/6 J mice were fed a high-fat diet (HFD) and LG2055 (1×10 8 or 1×10 10 CFU/mice, low-dose LG2055 (LP) or high-dose LG2055 (HP), respectively was administered orally. LG2055 supplementation significantly reduced white adipose tissues compared to the HFD group and modified plasma lipid profiles to normal levels. The anti-obesity efficacy of LG2055 was due to increased lipid excretion into feces by reducing the mRNA levels of fatty acid binding protein 1 (Fabp1), fatty acid binding protein 2 (Fabp2), fatty acid transport protein 4 (Fatp4), cluster of differentiation 36 (Cd36), and apolipoprotein 48 (ApoB48) in the small intestine. The body fat reduction inhibits ectopic lipid accumulation in the muscles, leading to improvements in muscle mass, grip strength, hind leg thickness, muscle protein levels, and muscle fiber size in both LP and HP groups. LG2055 increased gut microbiota diversity and elevated the levels of Bacteroidota, resulting in a lower Firmicutes/Bacteroidota ratio compared to the HFD group. Changes in the Bacteroidota showed a negative correlation with body fat and plasma free fatty acid (FFA) while exhibiting a positive correlation with lean body mass, grip strength, and hind leg thickness. Our results demonstrated the anti-obesity effects of LG2055 through the white adipose tissue (WAT)-muscle-gut axis, suggesting its potential as an anti-obesity agent., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier GmbH.)

Type 2 diabetes increases the risk of developing obesity. Although fulvic acid alleviates back fat thickness in pigs, the mechanism underlying its anti-obesity effect remains unclear. Therefore, we investigated the anti-obesity mechanism of fulvic acid using 3T3-L1 adipocytes. We examined the effects of fulvic acid on adipocyte differentiation, cell viability, and lipid accumulation using molecular techniques. Fulvic acid treatment significantly decreased intracellular lipid accumulation in 3T3-L1 cells during the differentiation compared with that in the control group. Western blotting revealed fulvic acid-induced downregulated expression of the adipocyte differentiation-related markers peroxisome proliferator-activated receptor gamma, CCAAT/enhancer-binding protein alpha, and sterol regulatory element-binding protein 1. The fulvic acid treatment decreased the expression of the lipid uptake-related markers fatty acid-binding protein 4 and the cluster of differentiation 36 in 3T3-L1 cells. Moreover, fulvic acid significantly increased cytosolic Ca 2+ concentration via Ca 2+ sequestration from the endoplasmic reticulum, enhanced Ca 2+ /calmodulin-dependent protein kinase II (CaMKII) activity, and upregulated AMP-activated protein kinase (AMPK), thereby reducing adipocyte differentiation. Conclusively, fulvic acid attenuates adipocyte differentiation by activating the Ca 2+ /CaMKⅡ/AMPK pathway, suggesting its anti-obesity potential., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: Crustacean shellfish is one of the eight most common food allergens, and crayfish is a highly valued shellfish species for consumption in China. However, the detailed allergen profile of crayfish remains unknown, with only four allergen groups reported in the WHO/IUIS allergen nomenclature database. In this study we aimed to identify novel allergens based on the Procambarus clarkii genome and to reveal its allergen profile for developing better diagnostic tools and treatments., Methods: We assembled the crayfish genome using both long-read and short-read sequencing data and identified putative allergens using the BLAST algorithm based on sequence homology. We employed bioinformatics tools to investigate the expression levels, gene structure, and synteny of these putative allergens. We also applied indirect enzyme-linked immunosorbent assay by using patients' sera to determine allergenicity and utilized proteomic methods to identify novel allergens., Results: We identified a total of 11 putative allergen groups, including all isoforms or homologs for each allergen group based on the genome and three putative allergens by using 2-dimensional (2D) mass spectrometry. We identified 2 novel allergens, pPro c 3.0301 and pPro c 6.0201, with immunoglobulin E reactivity of 33.3% and 20%, respectively., Conclusions: By providing a comprehensive understanding of the complete allergen profile, our study presents a foundation for comprehending P. clarkii- associated allergy. The knowledge could facilitate the implementation of a components-resolved diagnostic test and preventive immunotherapy based on molecular allergens for crayfish allergy., Competing Interests: There are no financial or other issues that might lead to conflict of interest., (Copyright © 2025 The Korean Academy of Asthma, Allergy and Clinical Immunology • The Korean Academy of Pediatric Allergy and Respiratory Disease.)

Mitochondrial dysfunction and macrophage dysregulation are well recognized as significant contributors to the pathogenesis of autoimmune diseases. However, the detailed mechanisms connecting these two factors remain poorly understood. This study hypothesizes that low but chronic interferon-gamma (IFN-γ) plays a critical role in these processes. To explore this, we utilized ARE-Del mice, a model characterized by sustained low-level IFN-γ expression and lupus nephritis (LN)-like symptoms. Age- and tissue-dependent gene expression analyses in ARE-Del mice revealed significant suppression of mitochondrial complex I components and activities, particularly in the kidneys. The genotype-dependent suppression of mitochondrial complex I indicates early disruption, which leads to macrophage dysfunction. Notably, remission restored gene expression of mitochondrial complex I and macrophage dysfunction in isolated renal macrophages from NZB/W lupus-prone mice. These findings suggest that chronic low-level IFN-γ disrupts mitochondrial complex I activity in macrophages, highlighting its role in the early pathogenesis of autoimmune diseases like lupus nephritis. This provides new insights into the molecular interactions underlying autoimmune pathogenesis and suggests potential targets for therapeutic intervention.

Long-term consumption of erythritol, a widely used sugar substitute, has been associated with increased risks of thrombosis and cardiometabolic diseases. In this study, we investigated the effects and mechanisms of allulose in mitigating these risks compared to erythritol using the clusterProfiler tool in R (version 4.12.6). Since a high-fat diet (HFD) is known to enhance platelet aggregation, we compared the pathways related to these processes between groups of mice treated with allulose and those treated with erythritol. While erythritol exacerbated HFD-induced increased platelet aggregation, allulose treatment significantly reduced it. Further analysis of platelet gene expression in sickle cell disease (SCD) patients to explore the potential of using sugar substitutes revealed that platelet coagulation mechanisms could be exacerbated by HFD. Additionally, the top up- and downregulated pathways in SCD were significantly reduced in the allulose-treated group compared to the erythritol group. Specific mechanisms related to this include the mitochondrial complex I and mitochondrial translational process as potential pathological factors in platelet coagulation related to SCD. Therefore, this study demonstrates that allulose may offer a safer alternative to erythritol in dietary applications, especially in individuals susceptible to thrombotic events, by modulating critical pathways associated with platelet function and mitochondrial activity.

Soil around mines contaminated with metal(loid) is not suitable for growing plants and it is necessary to select indigenous plants with tolerance for metal(loid) and ameliorate metal toxicity in soil using soil amendments. Therefore, the purpose of this study was to improve the soil environment to make it suitable for plant growth by treating chicken manure derived-biochar in soil contaminated with arsenic (As), cadmium (Cd), and lead (Pb). Biochar application increased soil pH and significantly reduced bioavailable As, Cd and Pb, thereby lowering toxicity in plants. Indigenous plant growth also increased by 30.2 and 91.3% in As and Pb contaminated soil under biochar treatment, respectively. Especially, Artemisia japonica Thunb. was effective for phytoextraction due to its accumulation of metals from contaminated soil, along with biochar application. Carex breviculmis R. Br. and Lespedeza cuneata (Dum. Cours.) G. Don. showed decreased above-ground Cd uptake by 57.6 and 44.9%, respectively, and As, Cd and Pb uptake by Juncus decipiens (Buchenau) Nakai decreased by 47.3, 65.7, and 94.1%, respectively, following biochar treatment. Juncus decipiens (Buchenau) Nakai, displayed tolerance in As, Cd and Pb contaminated soils and showed similar growth with or without biochar treatment, while the other three indigenous plant species failed to grow in the absence of biochar treatment. Therefore, J. decipiens is the most suitable candidate for the phytoremediation of metal-contaminated soils, and biochar further promoted plant health and growth., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Ltd. All rights reserved.)

Obesity is known to affect various tissues and contribute to conditions such as neuroinflammation. However, the specific mechanisms and time-dependent progression of these effects across different tissues remain unclear. In this study, we monitored gene expression at intervals to examine the effects of a high-fat diet (HFD) on brain, liver, adipose, and muscle tissues in male C57/BJ mice, with a particular focus on neuroinflammation. Early inflammatory responses exhibit a progression that starts in the liver, extends to adipose tissue, and subsequently involves muscle and brain tissues. Although the brain did not show significant gene expression of inflammatory responses, mechanisms leading to neuroinflammation increased after 24 weeks, possibly through systemic chronic inflammation (SCI). Notably, mitochondrial complex I activity serves as a biomarker to indicate the inflammatory transition from the liver to adipose and other tissues caused by SCI. These similar gene expression dynamics were also observed in the hippocampus of Alzheimer's patients and in an Alzheimer's mouse model treated with a HFD. These results suggest that initially, the brain suppresses inflammatory responses, including interferon-gamma (IFN-γ), more than other tissues in response to a HFD. However, at the onset of SCI, the brain eventually exhibits inflammatory dynamics similar to those of other tissues. This underscores the significance of our findings, indicating that the early kinetics of chronic IFN-γ response and mitochondrial complex I activity inhibition serve as crucial biomarkers, emerging early in various conditions, including obesity and aging.

Objectives: Propofol is commonly used for endoscopic sedation. However, it can induce adverse hemodynamic effects. Remimazolam is known to have a fast onset and short duration comparable to that of propofol, but with fewer effects on hemodynamics. We assessed the Oxygen Reserve Index to verify whether a sedative dose of remimazolam would better preserve oxygenation in the mild hyperoxic range than propofol in sedated patients undergoing diagnostic upper gastrointestinal endoscopy., Methods: Patients scheduled for diagnostic upper gastrointestinal endoscopy were enrolled. Patients were randomly assigned to either the remimazolam or propofol groups and received 0.1 mg/kg remimazolam or 0.5 mg/kg propofol, respectively. Bolus injections of either 0.05 mg/kg remimazolam or 0.25 mg/kg propofol were added if required. The primary outcome was the prevalence of oxygen reserve depletion, defined as the Oxygen Reserve Index decreasing to 0.00, and hypoxia defined as peripheral oxygen saturation falling to <94%., Results: Among 69 patients, the incidence of oxygen reserve depletion was significantly higher in the propofol group (65.7% vs. 38.2%, P = 0.022). Hypoxia was frequently observed in the propofol group, whereas none was observed in the remimazolam group (11.4% vs. 0%, P = 0.042). Additional sedative injections were frequently required to complete endoscopy in the propofol group. None of the patients in the remimazolam group required airway interventions. Nausea was frequent in the propofol group in the recovery room., Conclusion: Our results indicate that remimazolam is a safe and useful sedative for upper gastrointestinal endoscopy., (© 2024 The Author(s). Digestive Endoscopy published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

The significance of complex I of the electron transport chain (ETC) in the aging process is widely acknowledged; however, its specific impact on the development of sarcopenia in muscle remains poorly understood. This study elucidated the correlation between complex I inhibition and sarcopenia by conducting a comparative analysis of skeletal muscle gene expression in sarcopenia phenotypes from rats, mice, and humans. Our findings reveal a common mechanistic link across species, particularly highlighting the correlation between the suppression of complex I of ETC activity and dysregulated mitochondrial transcription and translation in sarcopenia phenotypes. Additionally, we observed macrophage dysfunction alongside abnormal metabolic processes within skeletal muscle tissues across all species, implicating their pathogenic role in the onset of sarcopenia. These discoveries underscore the importance of understanding the shared mechanisms associated with complex I of ETC in sarcopenia development. The identified correlations provide valuable insights into potential targets for therapeutic interventions aimed at mitigating the impact of sarcopenia, a condition with substantial implications for aging populations.

Local ablation for hepatocellular carcinoma, a non-surgical option that directly targets and destroys tumor cells, has advanced significantly since the 1990s. Therapies with different energy sources, such as radiofrequency ablation, microwave ablation, and cryoablation, employ different mechanisms to induce tumor necrosis. The precision, safety, and effectiveness of these therapies have increased with advances in guiding technologies and device improvements. Consequently, local ablation has become the first-line treatment for early-stage hepatocellular carcinoma. The lack of organized evidence and expert opinions regarding patient selection, preprocedure preparation, procedural methods, swift post-treatment evaluation, and follow-up has resulted in clinicians following varied practices. Therefore, an expert consensus-based practical recommendation for local ablation was developed by a group of experts in radiology and hepatology from the Research Committee of the Korean Liver Cancer Association in collaboration with the Korean Society of Image-Guided Tumor Ablation to provide useful information and guidance for performing local ablation and for the pre- and post-treatment management of patients.

Background and Aim: Transarterial chemoembolization (TACE) is one of the standard modalities used to treat unresectable hepatocellular carcinoma (HCC), but the effectiveness of TACE for treating patients with a solitary small (≤3 cm) HCC and well-preserved liver function has not been definitively established. This study aimed to determine the therapeutic impact of TACE in patients with these characteristics., Methods: This multicenter (four university hospitals) retrospective cohort study analyzed the medical records of 250 patients with a solitary small (≤3 cm) HCC and Child-Turcotte-Pugh (CTP) class A liver function diagnosed over 10 years. Posttreatment outcomes, including overall survival (OS), recurrence-free survival (RFS), and adverse events, were assessed following TACE therapy., Results: One hundred and thirty-eight of the 250 patients (55.2%) treated with TACE achieved complete remission (CR). Overall median OS was 77.7 months, and median OS was significantly longer in the CR group than in the non-CR group (89.1 vs. 58.8 months, P = 0.001). Median RFS was 19.1 months in the CR group. Subgroup analysis identified hypertension, an elevated serum albumin level, and achieving CR as significant positive predictors of OS, whereas diabetes, hepatitis c virus infection, and tumor size (>2 cm) were poor prognostic factors of OS., Conclusions: The study demonstrates the effectiveness of TACE as a viable alternative for treating solitary small (≤3 cm) HCC in CTP class A patients., (© 2024 The Authors. Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Natural killer (NK) cells are one of the key members of innate immunity that predominantly reside in the liver, potentiating immune responses against viral infections or malignant tumors. It has been reported that changes in cell numbers and function of NK cells are associated with the development and progression of chronic liver diseases (CLDs) including non-alcoholic fatty liver disease, alcoholic liver disease, and chronic viral hepatitis. Also, it is known that the crosstalk between NK cells and hepatic stellate cells plays an important role in liver fibrosis and cirrhosis. In particular, the impaired functions of NK cells observed in CLDs consequently contribute to occurrence and progression of hepatocellular carcinoma (HCC). Chronic infections by hepatitis B or C viruses counteract the anti-tumor immunity of the host by producing the sheddases. Soluble major histocompatibility complex class I polypeptide-related sequence A (sMICA), released from the cell surfaces by sheddases, disrupts the interaction and affects the function of NK cells. Recently, the MICA/B-NK stimulatory receptor NK group 2 member D (NKG2D) axis has been extensively studied in HCC. HCC patients with low membrane-bound MICA or high sMICA concentration have been associated with poor prognosis. Therefore, reversing the sMICA-mediated downregulation of NKG2D has been proposed as an attractive strategy to enhance both innate and adaptive immune responses against HCC. This review aims to summarize recent studies on NK cell immune signatures and its roles in CLD and hepatocellular carcinogenesis and discusses the therapeutic approaches of MICA/B-NKG2D-based or NK cell-based immunotherapy for HCC., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

This study investigated whether differences in survival rates and clinical outcomes exist in patients undergoing TKA by insurance type: National Health Insurance (NHI) vs. Medical Aid Program (MAP). This study conducted a retrospective analysis of 762 TKAs (NHI, n = 505; MAP, n = 257) with a mean follow-up of 8.4 ± 1.8 years. Patient-reported outcomes (PROMs) were evaluated using the American Knee Society's (AKS) score at the final follow-up. The survival rate of each group was analyzed using Kaplan-Meier survival analysis. Any postoperative complications and readmissions within 90 days of discharge were recorded and compared between the groups. There were no between-group differences in pre- to postoperative improvement in AKS scores. The estimated 10-year survival rates were 98.5% in the NHI group and 96.9% in the MAP group, respectively, with no significant differences ( p = 0.48). However, the length of hospital stay (LOS) was significantly longer in the MAP group than in the NHI group (13.4 days vs. 13.1 days, p = 0.03), and the transfer rate to other departments was significantly higher in the MAP group than in the NHI group (3.9% vs. 1.4%, p = 0.04). Readmission rates for orthopedic complications for 90 days were 3.0% in the NHI group and 3.5% in the MAP group, respectively ( p = 0.67). Patients' insurance type showed similar survival rates and clinical outcomes to those of primary TKA at a mean follow-up of 8.4 years, but the LOS and rate of transfer to other departments during hospitalization were influenced by insurance type.

Background: Chronic inflammation, which becomes more prevalent during aging, contributes to sarcopenia by reducing muscle mass and strength., Purpose: Wheat seedlings extract (WSE) is known for its various physiological activities, including anti-inflammation and antioxidant effects. However, its efficacy against sarcopenia is not well documented., Study Design: 8-week-old and 50-week-old C57BL/6 J mice were used as young control (YC group) and aged controls (AC group), respectively. Then, aged mice were randomly divided into 5 groups (WSE100mg/kg, WSE200mg/kg, WSE400mg/kg, and schizandrin as a positive control) and fed each experimental diet for 10 weeks., Method: We investigated the effects of WSE on muscle quality and protein homeostasis pathways based on improvements in mitochondrial function and chronic inflammation. We then used TNFα-treated C2C12 to investigate the effects of isoorientin (ISO) and isoschaftoside (ISS), the active substances of WSE, on the myogenic pathway., Results: We administered WSE to aging mice and observed an increase in muscle mass, thickness, protein content, and strength in mice treated with WSE at a dose of 200 mg/kg or 400 mg/kg. Furthermore, the administration of WSE led to a reduction in inflammatory factors (TNFα, IL-1, and IL-6) and an increase in mitochondrial biogenesis (p-AMPK/SIRT3/PGC1α) in muscle. This effect was also observed in TNFα-induced muscle atrophy in C2C12 cells, and we additionally identified the upregulation of myogenic regulatory factors, including Myf5, Myf6, MyoD, and myogenin, by WSE, ISO, and ISS., Conclusion: These findings suggest that WSE could function as a dietary anti-inflammatory factor and mitochondrial activator, potentially exerting modulatory effects on the metabolism and mechanical properties of skeletal muscles in the aging population. Furthermore, Our results demonstrate the potential value of ISO and ISS as functional food ingredients for preventing muscle atrophy., Competing Interests: Declaration of competing interest All authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier GmbH.)

Backgruound: We aimed to evaluate whether composite blood biomarkers including aldo-keto reductase family 1 member B10 (AKR1B10) and cytokeratin 18 (CK-18; a nonalcoholic steatohepatitis [NASH] marker) have clinically applicable performance for the diagnosis of NASH, advanced liver fibrosis, and high-risk NASH (NASH+significant fibrosis)., Methods: A total of 116 subjects including healthy control subjects and patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD) were analyzed to assess composite blood-based and imaging-based biomarkers either singly or in combination., Results: A composite blood biomarker comprised of AKR1B10, CK-18, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) showed excellent performance for the diagnosis of, NASH, advanced fibrosis, and high-risk NASH, with area under the receiver operating characteristic curve values of 0.934 (95% confidence interval [CI], 0.888 to 0.981), 0.902 (95% CI, 0.832 to 0.971), and 0.918 (95% CI, 0.862 to 0.974), respectively. However, the performance of this blood composite biomarker was inferior to that various magnetic resonance (MR)-based composite biomarkers, such as proton density fat fraction/MR elastography- liver stiffness measurement (MRE-LSM)/ALT/AST for NASH, MRE-LSM+fibrosis-4 index for advanced fibrosis, and the known MR imaging-AST (MAST) score for high-risk NASH., Conclusion: Our blood composite biomarker can be useful to distinguish progressive forms of NAFLD as an initial noninvasive test when MR-based tools are not available.

Background/objectives: Kaempferol (Ka) is one of the most widely occurring flavonoids found in large amounts in various plants. Ka has anti-obesity, antioxidant, and anti-inflammatory effects. Despite the numerous papers documenting the efficacy of Ka, some controversy remains. Therefore, this study examined the impact of Ka using 3T3-L1 and high-fat diet-induced obese mice., Materials/methods: 3T3-L1 cells were treated with 50 μM Ka from the initiation of 3T3-L1 differentiation at D0 until the completion of differentiation on D8. Thirty male mice (C57BL/6J, 4 weeks old) were divided into 3 groups: normal diet (ND), high-fat diet (HFD), and HFD + 0.02% (w/w) Ka (Ka) group. All mice were fed their respective diets ad libitum for 16 weeks. The mice were sacriced, and the plasma and hepatic lipid levels, white adipose tissue weight, hepatic glucose level, lipid level, and antioxidant enzyme activities were analyzed, and immunohistochemistry staining was performed., Results: Ka suppressed the hypertrophy of 3T3-L1 cells, and the Ka-supplemented mice showed a significant decrease in perirenal, retroperitoneal, mesenteric, and subcutaneous fat compared to the HFD group. Ka supplementation in high-fat diet-induced obese mice also improved the overall blood lipid concentration (total cholesterol, non-high-density lipoprotein-cholesterol, phospholipids, and apolipoprotein B). Ka supplementation in high-fat-induced obesity mice reduced hepatic steatosis and insulin resistance by modulating the hepatic lipid (glucose-6-phosphate dehydrogenase, fatty acid synthase, malic enzyme, phosphatidate phosphohydrolase, and β-oxidation) activities and glucose (glucokinase, phosphoenolpyruvate carboxykinase, and G6pase)-regulating enzymes. Ka supplementation ameliorated the erythrocyte and hepatic mitochondrial H 2 O 2 and inflammation levels (plasma tumor necrosis factor-alpha, monocyte chemoattractant protein-1, interleukin-6, and interferon-gamma and fibrosis of liver and epididymal fat)., Conclusion: Ka may be beneficial for preventing diet-induced obesity, inflammation, oxidative stress, and diabetes., Competing Interests: Conflict of Interest: The authors declare no potential conflicts of interests., (©2024 The Korean Nutrition Society and the Korean Society of Community Nutrition.)

Background and study aims: Endoscopic submucosal dissection is used to treat early gastric neoplasms. Compared with other endoscopic procedures, it requires higher doses of opioids, leading to adverse events during monitored anesthesia care. We investigated the correlations between clinicopathological characteristics and intraprocedural opioid requirements in patients who underwent endoscopic submucosal dissection under monitored anesthesia care. Patients and methods: The medical records of patients who underwent endoscopic submucosal dissection under monitored anesthesia care were retrospectively reviewed. The dependent variable was the total dose of fentanyl administered during the dissection, while independent variables were patient demographics, the American Society of Anesthesiologists physical status classification, preoperative vital sign data, and the pathological characteristics of the neoplasm. Correlations between variables were examined using multiple regression analysis. Results : The study included 743 patients. The median total fentanyl dose was 100 mcg. Younger age (coefficient -1.37; 95% confidence interval [CI] -1.78 to -0.95), male sex (16.12; 95% CI 6.99-25.24), baseline diastolic blood pressure (0.44; 95% CI 0.04-0.85), neoplasm length (1.63; 95% CI 0.90-2.36), and fibrosis (28.59; 95% CI 17.77-39.42) were positively correlated with the total fentanyl dose. Total fentanyl dose was higher in the differentiated (16.37; 95% CI 6.40-26.35) and undifferentiated cancers group (32.53; 95% CI 16.95-48.11) than in the dysplasia group; no significant differences were observed among the others. The mid-anterior wall (22.69; 95% CI 1.25-44.13), mid-posterior wall (29.65; 95% CI 14.39-44.91), mid-greater curvature (28.77; 95% CI 8.56-48.98), and upper groups (30.06; 95% CI 5.01-55.12) had higher total fentanyl doses than the lower group, whereas doses did not significantly differ for the mid-lesser curvature group. Conclusions : We identified variables that influenced opioid requirements during monitored anesthesia care for endoscopic submucosal dissection. These may help predict the needed opioid doses and identify factors affecting intraprocedural opioid requirements.

Background: Asian carps, a popular freshwater fish globally, are valued for their flavor and serve as a crucial protein source, especially for infants. However, grass carp parvalbumin is highly allergenic, surpassing the allergenicity of fish like salmon and cod. The allergenic potential of parvalbumin in other Asian carps remains unknown, underscoring the need for allergen identification to improve the precision of fish allergy diagnosis and treatment., Objective: To identify all parvalbumin homologs in Asian carps and investigate the role of gene divergence in allergenic homolog formation., Methods: Three annotated genomes of Asian carp, including grass carp, black carp and bighead carp, were constructed using a hybrid assembly approach. Through sequence homology at the genomic level, all the homologs of major fish allergens were identified. Bioinformatics tools were then employed to reveal the gene structures, expression levels, and protein conformations of parvalbumin., Results: Grass carp genome analysis showed nine parvalbumin homologs, with Cid&#95;PV2 most similar to Cten i 1. Bighead and black carp genomes had ten homologs, including potentially allergenic Mpi&#95;PV7 and Hno&#95;PV7. Tissue-specific expression patterns revealed alternative usage of parvalbumin homologs. Gene duplication events expanded parvalbumin copies in bony fish, with two gene clusters identified in Asian carp genomes., Conclusion: All the homologs of Asian carps' parvalbumin were accurately identified and gene divergence contributed to the formation of allergenic homologs. Together with a comprehensive gene sequence profile of carps' parvalbumin, those could be applied to achieve a more precise clinical diagnostic test.

Background/objectives: An increasing life expectancy in society has burdened healthcare systems substantially because of the rising prevalence of age-related metabolic diseases. This study compared the effects of animal protein hydrolysate (APH) and casein on metabolic diseases using aged mice., Materials/methods: Eight-week-old and 50-week-old C57BL/6J mice were used as the non-aged (YC group) and aged controls (NC group), respectively. The aged mice were divided randomly into 3 groups (NC, low-APH [LP], and high-APH [HP] and fed each experimental diet for 12 weeks. In the LP and HP groups, casein in the AIN-93G diet was substituted with 16 kcal% and 24 kcal% APH, respectively. The mice were sacrificed when they were 63-week-old, and plasma and hepatic lipid, white adipose tissue weight, hepatic glucose, lipid, and antioxidant enzyme activities, immunohistochemistry staining, and mRNA expression related to the glucose metabolism on liver and muscle were analyzed., Results: Supplementation of APH in aging mice resulted in a significant decrease in visceral fat (epididymal, perirenal, retroperitoneal, and mesenteric fat) compared to the negative control (NC) group. The intraperitoneal glucose tolerance test and area under the curve analysis revealed insulin resistance in the NC group, which was alleviated by APH supplementation. APH supplementation reduced hepatic gluconeogenesis and increased glucose utilization in the liver and muscle. Furthermore, APH supplementation improved hepatic steatosis by reducing the hepatic fatty acid and phosphatidate phosphatase activity while increasing the hepatic carnitine palmitoyltransferase activity. Furthermore, in the APH supplementation groups, the red blood cell (RBC) thiobarbituric acid reactive substances and hepatic H 2 O 2 levels decreased, and the RBC glutathione, hepatic catalase, and glutathione peroxidase activities increased., Conclusions: APH supplementation reduced visceral fat accumulation and alleviated obesity-related metabolic diseases, including insulin resistance and hepatic steatosis, in aged mice. Therefore, high-quality animal protein APH that reduces the molecular weight and enhances the protein digestibility-corrected amino acid score has potential as a dietary supplement for healthy aging., Competing Interests: Conflict of Interest: The authors declare no potential conflicts of interests., (©2024 The Korean Nutrition Society and the Korean Society of Community Nutrition.)

Pancreatic beta cells utilize Ca 2+ to secrete insulin in response to glucose. The glucose-dependent increase in cytosolic Ca 2+ concentration ([Ca 2+ ] C ) activates a series of insulin secretory machinery in pancreatic beta cells. Therefore, the amount of insulin secreted in response to glucose is determined in a [Ca 2+ ] C -dependent manner, at least within a moderate range. However, the demand for insulin secretion may surpass the capability of beta cells. Abnormal elevation of [Ca 2+ ] C levels beyond the beta-cell endurance capacity can damage them by inducing endoplasmic reticulum (ER) stress and cell death programs such as apoptosis. Therefore, while Ca 2+ is essential for the insulin secretory functions of beta cells, it could affect their survival at pathologically higher levels. Because an increase in beta-cell [Ca 2+ ] C is inevitable under certain hazardous conditions, understanding the regulatory mechanism for [Ca 2+ ] C is important. Therefore, this review discusses beta-cell function, survival, ER stress, and apoptosis associated with intracellular and ER Ca 2+ homeostasis., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Three bacterial strains, namely LPB0304 T , LPB0319 T and LPB0142 T , were isolated from coastal environments. The 16S rRNA gene sequences of the three isolates were found to show the highest sequence similarities to Massilia litorea (98.44 %), Marinobacter salinisoli (97.55 %) and Rhodobacter lacus (97.60 %), respectively. The low (<98.7 %) sequence similarities and tree topologies implied the novelty of the three isolates, representing novel genomic species of the genus Massilia , Marinobacter and Rhodobacter . Numerous biochemical and physiological features also supported the distinctiveness of the isolates from previously known species. Based on the phenotypic and phylogenetic data presented in this study, three novel species are suggested with the following names: Massilia litorea sp. nov. (LPB0304 T =KACC 21523 T =ATCC TSD-216 T ), Marinobacter salinisoli sp. nov. (LPB0319 T =KACC 21522 T =ATCC TSD-218 T ) and Rhodobacter xanthinilyticus sp. nov. (LPB0142 T =KACC 18892 T =JCM 31567 T ).

Background: Proton-pump inhibitors (PPIs) are the most effective drugs for treating acid-related disorders. However, once-daily dosing with conventional PPIs fail to fully control acid secretion over 24 h. This study aimed to compare the efficacy and safety of HIP1601 (dual delayed-release esomeprazole) and HGP1705 (delayed-release esomeprazole) in patients with erosive esophagitis (EE)., Methods: We enrolled 213 patients with EE randomized in a 1:1 ratio to receive 40 mg HIP1601 (n = 107) or HGP1705 (n = 106) once daily for 4 or 8 weeks. The primary endpoint was the EE healing rate, confirmed by endoscopy up to week 8. GERD-related symptoms and treatment-emergent adverse events were compared between both groups., Results: By week 8, the estimated healing rates of EE were 97.8% and 96.8% in the HIP1601 and HGP1705 groups, respectively, with a 95% confidence interval of -4.7 to 7.2. After 4 or 8 weeks of treatment, the EE healing rate at week 4, complete resolution rate of symptoms, time to sustained resolution of symptoms, and number of rescue medications used were similar in both groups. The proportion of heartburn- and acid regurgitation-free nights by week 4 were higher in the HIP1601 group compared to the HGP1705 group, but the difference did not reach clinical significance (87.7% vs. 85.8%, P = 0.514, 87.5% vs. 85.8%, P = 0.774). The number of adverse events did not differ significantly between the two groups., Conclusions: The efficacy and safety of HIP1601 40 mg were comparable to those of HGP1705 40 mg for the treatment of EE and symptomatic improvement of GERD., Trial Registration: NCT04080726 ( https://classic., Clinicaltrials: gov/ct2/show/NCT04080726 ), registration date: 25/10/2018., (© 2023. The Author(s).)

Age-related muscle loss and dysfunction, sarcopenia, is a common condition that results in poor quality of life in the elderly. Protein supplementation is a potential strategy for preventing sarcopenia and increasing muscle synthesis, but the effectiveness of protein type and level in improving sarcopenia is not well understood. In this study, we compared animal protein hydrolysate (APH), which has a high protein digestibility-corrected amino acid score (PDCAAS) and low molecular weight, with casein as a control group to investigate the effects and mechanisms of sarcopenia improvement, with a particular focus on the gut-muscle axis. APH supplementation improved age-related declines in muscle mass, grip strength, hind leg thickness, muscle protein level, muscle fiber size, and myokine levels, compared to the control group. In particular, levels of plasma cortisol, muscle lipids, and muscle collagen were markedly reduced by APH supplements in the aged mice. Furthermore, APH efficiently recovered the concentration of total SCFAs including acetic, propionic, and isovaleric acids decreased in aged mice. Finally, APH induced changes in gut microbiota and increased production of SCFAs, which were positively correlated with muscle protein level and negatively correlated with pro-inflammatory cytokines. In conclusion, APH can help to inhibit age-related sarcopenia by increasing muscle synthesis, inhibiting muscle breakdown, and potentially modulating the gut-muscle axis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Aims: Prolonged high levels of cytokines, glucose, or free fatty acids are associated with diabetes, elevation of cytosolic Ca 2+ concentration ([Ca 2+ ] C ), and depletion of Ca 2+ concentration in the endoplasmic reticulum (ER) of pancreatic beta cells. This Ca 2+ imbalance induces ER stress and apoptosis. Lupenone, a lupan-type triterpenoid, is beneficial in diabetes; however, its mechanism of action is yet to be clarified. This study evaluated the protective mechanism of lupenone against thapsigargin-induced ER stress and apoptosis in pancreatic beta cells., Materials and Methods: MIN6, INS-1, and native mouse islet cells were used. Western blot for protein expressions, measurement of [Ca 2+ ] C , and in vivo glucose tolerance test were mainly performed., Key Findings: Thapsigargin increased the protein levels of cleaved caspase 3, cleaved PARP, and the phosphorylated form of JNK, ATF4, and CHOP. Thapsigargin increased the interaction between stromal interaction molecule1 (Stim1) and Orai1, enhancing store-operated calcium entry (SOCE). SOCE is further activated by protein tyrosine kinase 2 (Pyk2), which is Ca 2+ -dependent and phosphorylates the tyrosine residue at Y 361 in Stim1. Lupenone inhibited thapsigargin-mediated Pyk2 activation, suppressed [Ca 2+ ] C , ER stress, and apoptosis. Lupenone restored impaired glucose-stimulated insulin secretion effectuated by thapsigargin and glucose intolerance in a low-dose streptozotocin-induced diabetic mouse model., Significance: These results suggested that lupenone attenuated thapsigargin-induced ER stress and apoptosis by inhibiting SOCE; this may be due to the hindrance of Pyk2-mediated Stim1 tyrosine phosphorylation. In beta cells that are inevitably exposed to frequent [Ca 2+ ] C elevation, the attenuation of abnormally high SOCE would be beneficial for their survival., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: Gastric cancer (GC) is among the most prevalent and fatal cancers worldwide. National cancer screening programs in countries with high incidences of this disease provide medical aid beneficiaries with free-of-charge screening involving upper endoscopy to detect early-stage GC. However, the coronavirus disease 2019 (COVID-19) pandemic has caused major disruptions to routine healthcare access. Thus, this study aimed to assess the impact of COVID-19 on the diagnosis, overall incidence, and stage distribution of GC., Materials and Methods: We identified patients in our hospital cancer registry who were diagnosed with GC between January 2018 and December 2021 and compared the cancer stage at diagnosis before and during the COVID-19 pandemic. Subgroup analyses were conducted according to age and sex. The years 2018 and 2019 were defined as the "before COVID" period, and the years 2020 and 2021 as the "during COVID" period., Results: Overall, 10,875 patients were evaluated; 6,535 and 4,340 patients were diagnosed before and during the COVID-19 period, respectively. The number of diagnoses was lower during the COVID-19 pandemic (189 patients/month vs. 264 patients/month) than before it. Notably, the proportion of patients with stages 3 or 4 GC in 2021 was higher among men and patients aged ≥40 years., Conclusions: During the COVID-19 pandemic, the overall number of GC diagnoses decreased significantly in a single institute. Moreover, GCs were in more advanced stages at the time of diagnosis. Further studies are required to elucidate the relationship between the COVID-19 pandemic and the delay in the detection of GC worldwide., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2023. Korean Gastric Cancer Association.)

D-allulose, a rare sugar, has been proposed to have potential benefits in addressing metabolic disorders such as obesity and type 2 diabetes (T2D). However, the precise mechanisms underlying these effects remain poorly understood. We aimed to elucidate the mechanisms by which D-allulose influences obesity-induced insulin resistance. We conducted gene set enrichment analysis on the liver and white adipose tissue of mice exposed to a high-fat diet (HFD) along with the white adipose tissue of individuals with obesity. Our study revealed that D-allulose effectively suppressed IFN-γ, restored chemokine signaling, and enhanced macrophage function in the livers of HFD-fed mice. This implies that D-allulose curtails liver inflammation, alleviating insulin resistance and subsequently impacting adipose tissue. Furthermore, D-allulose supplementation improved mitochondrial NADH homeostasis and translation in both the liver and white adipose tissue of HFD-fed mice. Notably, we observed decreased NADH homeostasis and mitochondrial translation in the omental tissue of insulin-resistant obese subjects compared to their insulin-sensitive counterparts. Taken together, these results suggest that supplementation with allulose improves obesity-induced insulin resistance by mitigating the disruptions in macrophage and mitochondrial function. Furthermore, our data reinforce the crucial role that mitochondrial energy expenditure plays in the development of insulin resistance triggered by obesity.

Obesity-induced chronic inflammation has been linked to several autoimmune diseases, including rheumatoid arthritis, type 1 diabetes, and multiple sclerosis. The underlying mechanisms are not yet fully understood, but it is believed that chronic inflammation in adipose tissue can lead to the production of pro-inflammatory cytokines and chemokines, which can trigger immune responses and contribute to the development of autoimmune diseases. However, the underlying mechanisms that lead to the infiltration of immune cells into adipose tissue are not fully understood. In this study, we observed a time-dependent response to a high-fat diet in the liver and epididymal white adipose tissue using gene set enrichment analysis. Our findings revealed a correlation between early abnormal innate immune responses in the liver and late inflammatory response in the adipose tissue, that eventually leads to systemic inflammation. Specifically, our data suggest that the dysregulated NADH homeostasis in the mitochondrial matrix, interacting with the mitochondrial translation process, could serve as a sign marking the transition from liver inflammation to adipose tissue inflammation. Taken together, our study provides valuable insights into the molecular mechanisms underlying the development of chronic inflammation and associated autoimmune diseases in obesity., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)