A Phase II Study About Efficacy and Safety of the Continuous IntraVenous Infusion of Ketamine as Adjuvant to Opioids in Terminally Ill Cancer Patients With Refractory Cancer Pain (CIVIK Trial).

BACKGROUND: Ketamine has been used to control refractory cancer pain as an adjuvant to opioids. We conducted a prospective phase II study to investigate the efficacy and safety of 5-day continuous intravenous infusion (CIVI) of Ketamine in terminally ill cancer patients with refractory cancer pain. METHODS: Hospitalized terminally ill cancer patients with refractory cancer pain were enrolled. Refractory cancer pain was indicated by requirements for 4 or more rescue opioids or pain intensity using numerical rating scale > personalized pain goal (PPG) despite of intravenous morphine equivalent daily dose (IV MEDD) ≥ 120 mg/day. The CIVI of ketamine was increased from .05 mg/kg/hour to .5 mg/kg/hour by .05 every 8 hours if pain intensity exceeded PPG or if number of rescue opioids ≥2 during prior 8 hours was required. The primary end-point was overall pain response rate, which indicates complete response (both rescue opioid ≤3/day and pain intensity ≤ PPG) plus partial response (rescue opioid ≤3/day), without unacceptable toxicities. RESULTS: Among 21 eligible patients enrolled between September 2019 and January 2023, 20 were analyzed. Most pain mechanisms were mixed type (n = 15, 75%), with neuropathic component (n = 17, 85%). The baseline background opioids were IV MEDD 186 mg/24hour (range, 124-592), number of rescue opioids was 6 (IQR, 5-9), and median PPG was 4 (IQR, 3-4). The overall pain response rate was 50% (n = 10) including 40% (n = 8) for complete pain response and 10% (n = 2) for partial pain response. CONCLUSION: This study showed efficacy of gradually increasing CIVI of ketamine for terminally ill cancer patients with refractory cancer pain. CIVI of ketamine could be a useful tool in these patients considering the limited treatment options. (NCT03362073, Initial Release: November 15, 2017).

Relationship between Pulse Pressure and Handgrip Strength in the Korean Population: A Nationwide Cross-Sectional Study.

Background: Sarcopenia is defined as the loss of muscle mass and strength and low physical performance, and it is closely related to the risk of cardiovascular disease and mortality. Pulse pressure (PP) is a biomarker of arterial stiffness and compliance. Elevated PP levels increase the risk of cardiovascular diseases and all-cause mortality. Nevertheless, the association between PP and sarcopenia has not yet been clearly established. Methods: Participant data were extracted from the Korea National Health and Nutrition Examination Survey conducted from 2014 to 2020. The study population was classified into three groups (PP < 40 mmHg, 40 mmHg ≤ PP < 60 mmHg, and PP ≥ 60 mmHg). PP was calculated by deducting the diastolic blood pressure from the systolic blood pressure. For handgrip strength, the maximum value measured with a grip dynamometer was adopted (weak handgrip strength: <28 kg for men, <18 kg for woman; normal handgrip strength: ≥28 kg for men, ≥18 kg for women). To determine the relationship between PP and the prevalence of weak handgrip strength, multiple logistic regression analysis was performed after adjusting for possible confounding factors. Results: The higher PP group had a higher age, body mass index; systolic blood pressure, prevalence of hypertension, diabetes, hyperlipidemia, and metabolic syndrome, and maximum handgrip strength. In all models, the prevalence of weak handgrip strength was significantly higher in the group with PP ≥ 60 mmHg compared to the control group (PP < 40 mmHg). Conclusions: Elevated PP was significantly associated with a higher prevalence of weak muscle strength. Thus, PP monitoring may be used to identify individuals at risk of sarcopenia and is helpful in improving health outcomes.

Analyzing circulating tumor cells and epithelial-mesenchymal transition status of papillary thyroid carcinoma patients following thyroidectomy: a prospective cohort study.

BACKGROUND: This study investigated the prevalence and subtype distribution of circulating tumor cells (CTCs) in patients with papillary thyroid cancer (PTC) before and after thyroidectomy to determine the potential of CTC count as a non-invasive marker of the efficacy of surgical treatment in PTC. MATERIALS AND METHODS: Between January 2021 and January 2022, 62 PTC patients who underwent thyroidectomy at OOOOOOO Hospital were prospectively evaluated. Peripheral blood samples (7.5 ml) were collected from each patient for CTC analysis before surgery and at 2 weeks and 3 months after surgery. CTC count and the distribution of CTC subtypes, including epithelial, epithelial-mesenchymal, and mesenchymal phenotypes, were analyzed using the negative selection method and immunofluorescence staining. The relationship between CTC count and clinicopathological characteristics was analyzed before and after surgery. RESULTS: Before surgery, CTCs were detected in 87% (54/62) of patients; the mean CTC count was 8.0 and the median was 5.0 in 7.5 ml of peripheral blood. The mesenchymal or epithelial-mesenchymal phenotypes were predominant. After thyroidectomy, the mean and median CTC count values decreased to 5.3 and 2.5, respectively, at 2 weeks and to 4.3 and 3.0, respectively, at 3 months. This postoperative reduction in CTCs was more pronounced in patients with lymphatic invasion, lymph node metastasis, or BRAF V600E mutation. CONCLUSION: CTCs were detected in patients with PTC with a predominance of cells undergoing epithelial-mesenchymal transition. The CTC count decreased postoperatively, suggesting that liquid biopsy with CTC detection could be a valuable non-invasive tool for monitoring the efficacy of surgery in PTC.

Hepatoprotective Effect of Lactiplantibacillus plantarum DSR330 in Mice with High Fat Diet-Induced Nonalcoholic Fatty Liver Disease.

Lactiplantibacillus plantarum DSR330 (DSR330) has been examined for its antimicrobials production and probiotics. In this study, the hepatoprotective effects of DSR330 were examined against non-alcoholic fatty liver disease (NAFLD) in a high-fat diet (HFD)-fed C57BL/6 mouse model. To induce the development of fatty liver, a HFD was administered for five weeks, and then silymarin (positive control) or DSR330 (108 or 109 CFU/day) was administered along with the HFD for seven weeks. DSR330 significantly decreased body weight and altered serum and hepatic lipid profiles, including a reduction in triglyceride, total cholesterol, and low-density lipoprotein cholesterol levels compared to those in the HFD group. DSR330 significantly alleviated HFD-related hepatic injury by inducing morphological changes and reducing the levels of biomarkers, including AST, ALT, and ALP. Additionally, DSR330 alleviated the expression of SREBP-1c, ACC1, FAS, ACO, PPARα, and CPT-1 in liver cells. Insulin and leptin levels were decreased by DSR330 compared to those observed in the HFD group. However, adiponectin levels were increased, similar to those observed in the ND group. These results demonstrate that L. plantarum DSR330 inhibited HFD-induced hepatic steatosis in mice with NAFLD by modulating various signaling pathways. Hence, the use of probiotics can lead to hepatoprotective effects.

Oral Nutritional Supplements Reduce Body Weight Loss after Gastrectomy in Patients with Gastric Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

This systematic review and meta-analysis aimed to summarize the effects of oral nutritional supplements (ONSs) on body weight loss (BWL) after gastrectomy. A systematic search was conducted across the PubMed, Cochrane, and Embase databases through May 2023. The study inclusion criteria were as follows: (1) studies on interventions including ONSs after gastrectomy in patients with gastric cancer; (2) studies in which comparisons were specified according to standard, regular, or usual postoperative diets; and (3) randomized controlled trial studies including outcomes measured as mean differences in BWL. The data were pooled using the random-effects model and expressed as mean differences with 95% confidence intervals (CI). Based on data from seven studies including 1743 patients (891 for ONSs and 852 for the control), the overall pooled mean difference was 0.848 (95% CI: 0.466 to 1.230) and the Higgins I2 value was 86.0%. This systematic review and meta-analysis is the first study to show that ONSs are significantly associated with reducing BWL, compared with standard diets, after gastrectomy in patients with gastric cancer. Furthermore, we found that ONSs were more effective in patients with lower nutritional kilocalorie intake after gastrectomy.

Urological complications after COVID 19 vaccine according to age, sex and manufacturer.

OBJECTIVES: To examine the effects of age, sex, and type of COVID-19 vaccine on urological complications after vaccination with COVID-19. MATERIALS AND METHODS: We used the Vaccine Adverse Event Reporting System (VAERS) data from December 2020 to August 2022 to analyze urological symptoms post-vaccination adverse events (AEs) associated with COVID-19 vaccines authorized for the U.S. POPULATION: We collected AEs after 1-2 dose vaccination in VAERS, but not those after an additional booster shot. Age was divided into three groups (< 18 years, 18-64 years, and > 64 years), and compared incidence of AEs after vaccination with either mRNA vaccine (mRNA-1273, Moderna; and BNT162b2, Pfizer-BioNTech) or a viral vector vaccine (JNJ-78436735, Janssen/Johnson and Johnson) as reported in VAERS data. RESULTS: Cumulative incidence rates (CIRs) of LUTS, voiding symptom, storage symptom, infection, and hematuria were 0.057, 0.282, 0.223, 1.245, and 0.214, respectively. By gender, CIRs OF LUTS, storage symptom, and infection were statistically significantly higher in women, whereas CIRs of voiding symptom and hematuria were statistically significantly higher in men. CIRs of AEs per 100,000 in age groups of < 18 years, 18-64 years, and > 64 years were 0.353, 1.403, and 4.067, respectively. All AE types except for voiding symptom displayed the highest CIRs in the Moderna vaccine group. CONCLUSIONS: Based on an updated analysis of available data, the prevalence of urologic complications following administration of COVID-19 vaccines is low. However, specific urologic complications such as gross hematuria are not low in incidence.

HIV-1 virological synapse formation enhances infection spread by dysregulating Aurora Kinase B.

HIV-1 spreads efficiently through direct cell-to-cell transmission at virological synapses (VSs) formed by interactions between HIV-1 envelope proteins (Env) on the surface of infected cells and CD4 receptors on uninfected target cells. Env-CD4 interactions bring the infected and uninfected cellular membranes into close proximity and induce transport of viral and cellular factors to the VS for efficient virion assembly and HIV-1 transmission. Using novel, cell-specific stable isotope labeling and quantitative mass spectrometric proteomics, we identified extensive changes in the levels and phosphorylation states of proteins in HIV-1 infected producer cells upon mixing with CD4+ target cells under conditions inducing VS formation. These coculture-induced alterations involved multiple cellular pathways including transcription, TCR signaling and, unexpectedly, cell cycle regulation, and were dominated by Env-dependent responses. We confirmed the proteomic results using inhibitors targeting regulatory kinases and phosphatases in selected pathways identified by our proteomic analysis. Strikingly, inhibiting the key mitotic regulator Aurora kinase B (AURKB) in HIV-1 infected cells significantly increased HIV activity in cell-to-cell fusion and transmission but had little effect on cell-free infection. Consistent with this, we found that AURKB regulates the fusogenic activity of HIV-1 Env. In the Jurkat T cell line and primary T cells, HIV-1 Env:CD4 interaction also dramatically induced cell cycle-independent AURKB relocalization to the centromere, and this signaling required the long (150 aa) cytoplasmic C-terminal domain (CTD) of Env. These results imply that cytoplasmic/plasma membrane AURKB restricts HIV-1 envelope fusion, and that this restriction is overcome by Env CTD-induced AURKB relocalization. Taken together, our data reveal a new signaling pathway regulating HIV-1 cell-to-cell transmission and potential new avenues for therapeutic intervention through targeting the Env CTD and AURKB activity.

Association between weekend catch-up sleep and hyperuricemia with insufficient sleep in postmenopausal Korean women: a nationwide cross-sectional study.

OBJECTIVE: Hyperuricemia is associated with metabolic and cardiovascular diseases and mortality. Efforts to lower the risk of hyperuricemia in various ways are needed as the prevalence of these diseases increases in postmenopausal women. Studies have shown that one of these methods is associated with adequate sleep duration, which is related to a low risk of hyperuricemia. Considering that it is difficult for people to get enough sleep in modern society, this study hypothesized that weekend catch-up sleep could be an alternative. To our knowledge, no past study has investigated the relation between weekend catch-up sleep and hyperuricemia in postmenopausal women. Hence, the aim of this research was to estimate the relation between weekend catch-up sleep and hyperuricemia with insufficient sleep in postmenopausal women during weekday or workday. METHODS: This study included 1,877 participants extracted from the Korea National Health and Nutrition Examination Survey VII. The study population was divided into weekend catch-up sleep and non-weekend catch-up sleep groups. Odds ratios with 95% confidence intervals were derived using multiple logistic regression analysis. RESULTS: Weekend catch-up sleep had a significantly lower prevalence of hyperuricemia after adjusting for confounders (odds ratio, 0.758 [95% confidence interval, 0.576-0.997]). In a subgroup analysis, weekend catch-up sleep of 1 to 2 hours was significantly correlated with a lower prevalence of hyperuricemia after adjusting for confounders (odds ratio: 0.522 [95% confidence interval, 0.323-0.845]). CONCLUSIONS: Weekend catch-up sleep had a decreased prevalence of hyperuricemia in postmenopausal women with sleep deprivation.

GDNF family receptor alpha-like antagonist antibody alleviates chemotherapy-induced cachexia in melanoma-bearing mice.

BACKGROUND: Patients with cancer undergoing chemotherapy experience cachexia with anorexia, body weight loss, and the depletion of skeletal muscles and adipose tissues. Effective treatment strategies for chemotherapy-induced cachexia are scarce. The growth differentiation factor 15 (GDF15)/GDNF family receptor alpha-like (GFRAL)/rearranged during transfection (RET) axis is a critical signalling pathway in chemotherapy-induced cachexia. In this study, we developed a fully human GFRAL antagonist antibody and investigated whether it inhibits the GDF15/GFRAL/RET axis, thereby alleviating chemotherapy-induced cachexia in tumour-bearing mice. METHODS: Anti-GFRAL antibodies were selected via biopanning, using a human combinatorial antibody phage library. The potent GFRAL antagonist antibody A11 was selected via a reporter cell assay and its inhibitory activity of GDF15-induced signalling was evaluated using western blotting. To investigate the in vivo function of A11, a tumour-bearing mouse model was established by inoculating 8-week-old male C57BL/6 mice with B16F10 cells (n = 10-16 mice per group). A11 was administered subcutaneously (10 mg/kg) 1 day before intraperitoneal treatment with cisplatin (10 mg/kg). Animals were assessed for changes in food intake, body weight, and tumour volume. Plasma and key metabolic tissues such as skeletal muscles and adipose tissues were collected for protein and mRNA expression analysis. RESULTS: A11 reduced serum response element-luciferase reporter activity up to 74% (P < 0.005) in a dose-dependent manner and blocked RET phosphorylation up to 87% (P = 0.0593), AKT phosphorylation up to 28% (P = 0.0593) and extracellular signal regulatory kinase phosphorylation up to 75% (P = 0.0636). A11 inhibited the action of cisplatin-induced GDF15 on the brainstem and decreased GFRAL-positive neuron population expressing c-Fos in the area postrema and nucleus of the solitary tract by 62% in vivo (P < 0.05). In a melanoma mouse model treated with cisplatin, A11 recovered anorexia by 21% (P < 0.05) and tumour-free body weight loss by 13% (P < 0.05). A11 significantly improved the cisplatin-induced loss of skeletal muscles (quadriceps: 21%, gastrocnemius: 9%, soleus: 13%, P < 0.05) and adipose tissues (epididymal white adipose tissue: 37%, inguinal white adipose tissue: 51%, P < 0.05). CONCLUSIONS: Our study suggests that GFRAL antagonist antibody may alleviate chemotherapy-induced cachexia, providing a novel therapeutic approach for patients with cancer experiencing chemotherapy-induced cachexia.

The Role of Some Vitamins in Respiratory-related Viral Infections: A Narrative Review.

This study aimed to find out the effect of vitamins on respiratory-related viral infections, including coronavirus disease 2019 (COVID-19), through the literature reviews. From January 2000 to June 2021, the studies (cohort studies, cross-sectional studies, case-control studies, randomized control trials) related to vitamins (vitamin A, D, E, C, B6, folate, and B12) and COVID-19/severe acute respiratory syndrome/Middle East respiratory syndrome/cold/influenza were selected from the PubMed, Embase, and Cochrane libraries and analyzed. The relationship between vitamins and virus-related respiratory diseases was identified. Through the review, 39 studies were selected on vitamin D, one study on vitamin E, 11 studies on vitamin C, and 3 studies on folate. Regarding COVID-19, 18 studies on vitamin D, 4 studies on vitamin C, and 2 studies on folate showed significant effects of the intake of these nutrients in preventing COVID-19. Regarding colds and influenza, 3 studies on vitamin D, 1 study on vitamin E, 3 studies on vitamin C, and 1 study on folate demonstrated that the intake of these nutrients significantly prevents these diseases. Therefore, this review suggested the intake of vitamins D, E, C, and folate is important for preventing respiratory diseases related to viruses, such as COVID-19, colds, and influenza. The relationship between these nutrients and virus-related respiratory diseases should be continuously monitored in the future.

Association between pulse pressure and low muscle mass in Korean adults: A nationwide cross-sectional study.

Sarcopenia is characterized by a loss of muscle mass and strength and is associated with a high risk of cardiovascular events and increased mortality. Pulse pressure (PP) serves as a marker for changes in heart structure and function, as well as arterial stiffness. A high PP also increases the risk of cardiovascular disease and all-cause mortality. However, the relationship between PP and sarcopenia is poorly understood. We used the data of participants of the Korea National Health and Nutrition Examination Survey (KNHANES) of 2008 to 2011. Participants were divided into a control group (PP < 40 mm Hg) and a high-PP group (PP ≥ 40 mm Hg). PP was calculated by subtracting the diastolic blood pressure (DBP) from the systolic blood pressure (SBP), and the low muscle index was assessed using appendicular skeletal muscle mass (ASM) normalized by body mass index (BMI). Multiple logistic regression analyses were performed to examine the association between PP and the prevalence of low muscle mass, adjusting for potential confounders. The high-PP group had a higher age, SBP, DBP, and prevalence of hypertension, diabetes and hyperlipidemia than the control group. The high-PP group had a higher prevalence of low muscle mass than the control group in all models. A high PP is significantly associated with a higher prevalence of low muscle mass. Therefore, PP monitoring may help identify individuals at risk of sarcopenia and guide interventions to improve health outcomes.

Choline intake and its dietary reference values in Korea and other countries: a review.

Choline is a water-soluble organic compound that is important for the normal functioning of the body. It is an essential dietary component as de novo synthesis by the human body is insufficient. Since the United States set the Adequate Intakes (AIs) for total choline as dietary reference values in 1998, Australia, China, and the European Union have also established the choline AIs. Although choline is clearly essential to life, the 2020 Dietary Reference Intakes for Koreans (KDRIs) has not established the values because very few studies have been done on choline intake in Koreans. Since choline intake levels differ by race and country, human studies on Koreans are essential to set KDRIs. Therefore, the present study was undertaken to provide basic data for developing choline KDRIs in the future by analyzing data on choline intake in Koreans to date and reference values of choline intake and dietary choline intake status by country and race.

Antioxidant and Immune-Modulating Activities of Egg Yolk Protein Extracts.

Egg yolk is widely used to extract lecithin, which is utilized in the food and cosmetics industry. After lecithin is removed, the rest of egg yolk is generated as a by-product. Thus, it is necessary to properly utilize it. In this study, egg yolk protein extracts were produced using ethanol (EYE-E) and water (EYE-W). Their antioxidant and immunomodulatory effects were then evaluated. Antioxidant activities of EYE-E and EYE-W were determined using cellular antioxidant capacity (CAC) assay and comet assay. EYE-E and EYE-W showed significant (p<0.05) scavenging effects on intracellular reactive oxygen species (ROS) in a dose dependent manner. At a concentration of 50 µg/mL, EYE-W showed higher (p<0.05) antioxidant activity than EYE-E. EYE-E and EYE-W also exhibited protective effects against DNA damage caused by oxidative stress. After treatment with EYE-E and EYE-W, DNA damage level of 48.7% due to oxidative stress was decreased to 36.2% and 31.8% levels, respectively. In addition, EYE-E and EYE-W showed immunomodulatory effects by regulating Th1 cytokines (TNF-α and IL-2) and Th2 cytokines (IL-10 and IL-4) in Balb/c mouse splenocytes. These data suggest that EYE-E and EYE-W could be used as functional food ingredients with excellent antioxidant and immunomodulatory activities in the food industry.

Gut Microbiome in Non-Alcoholic Fatty Liver Disease: From Mechanisms to Therapeutic Role.

Non-alcoholic fatty liver disease (NAFLD) is considered to be a significant health threat globally, and has attracted growing concern in the research field of liver diseases. NAFLD comprises multifarious fatty degenerative disorders in the liver, including simple steatosis, steatohepatitis and fibrosis. The fundamental pathophysiology of NAFLD is complex and multifactor-driven. In addition to viruses, metabolic syndrome and alcohol, evidence has recently indicated that the microbiome is related to the development and progression of NAFLD. In this review, we summarize the possible microbiota-based therapeutic approaches and highlight the importance of establishing the diagnosis of NAFLD through the different spectra of the disease via the gut-liver axis.

The Lactobacillus as a Probiotic: Focusing on Liver Diseases.

Over the past decade, scientific evidence for the properties, functions, and beneficial effects of probiotics for humans has continued to accumulate. Interest in the use of probiotics for humans has increased tremendously. Among various microorganisms, probiotics using bacteria have been widely studied and commercialized, and, among them, Lactobacillus is representative. This genus contains about 300 species of bacteria (recently differentiated into 23 genera) and countless strains have been reported. They improved a wide range of diseases including liver disease, gastrointestinal diseases, respiratory diseases, and autoimmune diseases. Here, we intend to discuss in depth the genus Lactobacillus as a representative probiotic for chronic liver diseases.

The Status of Enteral Nutrition Formula Use by Dietitians in Hospitals Within Busan and Gyeongnam Area.

This study was conducted to analyze the status of medical food selection process in hospitals within Busan and Gyeongnam area. The survey was distributed to 396 hospitals (general, tertiary and long-term care hospitals) and finally 68 surveys were used for analysis. The questionnaire consisted of 9 general items and 10 items related to enteral nutrition (EN). From the survey we found out that general hospitals and tertiary hospitals normally hire clinical dietitian, while long-term care hospitals hire dietitians with no further qualifications (χ2 = 27.918, p < 0.001). A significant relationship was found between hospital size and the priority for choosing medical foods for patients (χ2 = 11.852, p < 0.05). In general and tertiary hospitals, medical foods were provided exactly according to the doctor's prescription, whereas in long-term care hospitals, only half followed the doctor's direction and half of them provided the products that has been conventionally used. There was also a significant relationship between hospital size and the method for determination of nutrition requirements (χ2 = 20.496, p < 0.001). Finally, the priority of considerations when developing a 'medical food guidelines' was shown in the following order; 1) the type of medical food that can be selected according to the disease state, 2) the nutrient content and comparison table for commercial products, and 3) how to manage complications that may occur when supplying medical food for patients. Developing an EN practice guideline for making a sensible selection of medical foods will provide a valuable information for better patient care.

Egg Yolk Protein Water Extracts Modulate the Immune Response in BALB/c Mice with Immune Dysfunction Caused by Forced Swimming.

The objective of this study was to determine the immunomodulatory effects of egg yolk protein-water extract (EYW) on splenocyte proliferation, cytokine secretion, immunoglobulin production, and NK cell cytotoxic activity in BALB/c mice. The forced swimming test (FST) was used to provide a model for suppressing immune regulation. The proliferation of B cells in the EYW supplementation group was significantly increased from the level to which it was reduced by the FST (from 40.9% to 81.8%, p < 0.05). EYW supplementation affected cytokine secretion of splenocytes. Levels of interleukin (IL)-2 and IL-10-as Th1 and Th2 cytokines, respectively-were decreased after the FST. However, EYW supplementation showed that secretion levels of these cytokines were significantly increased to pre-FST levels (p < 0.05). The production of immunoglobulins (IgA and IgG) was increased abnormally after the FST, whereas EYW supplementation significantly decreased it to pre-FST levels (p < 0.05). EYW supplementation also improved NK cell cytotoxic activity against YAC-1 tumor cells compared to the PC group (p < 0.05). These data suggest that EYW has potential as an immunomodulatory agent in the food and/or pharmaceutical industries.

T Cell Subsets and Natural Killer Cells in the Pathogenesis of Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is a condition characterized by hepatic accumulation of excess lipids. T cells are commonly classified into various subsets based on their surface markers including T cell receptors, type of antigen presentation and pathophysiological functions. Several studies have implicated various T cell subsets and natural killer (NK) cells in the progression of NAFLD. While NK cells are mainly components of the innate hepatic immune system, the majority of T cell subsets can be part of both the adaptive and innate systems. Several studies have reported that various stages of NAFLD are accompanied by the accumulation of distinct T cell subsets and NK cells with different functions and phenotypes observed usually resulting in proinflammatory effects. More importantly, the overall stimulation of the intrahepatic T cell subsets is directly influenced by the homeostasis of the gut microbiota. Similarly, NK cells have been found to accumulate in the liver in response to pathogens and tumors. In this review, we discussed the nature and pathophysiological roles of T cell subsets including γδ T cells, NKT cells, Mucosal-associated invariant T (MAIT) cells as well as NK cells in NAFLD.

Effects of Calcium Fortified Beverage Intake on Insulin Sensitivity and Antioxidant Metabolism in Healthy Elderly.

Calcium, one of the most important nutrients, determines the quality of life of the elderly. It has been reported that 7 out of 10 people over the age of 60 have insufficient calcium intake. The purpose of this study was to evaluate the effect of calcium fortified beverage (CFB) intake on insulin sensitivity and antioxidant metabolism in healthy elderly. A crossover clinical trial was performed and antioxidant status of healthy elderly (age above 65 years, n = 8) was analyzed. Subjects did not take CFB for 0-3 weeks. They then took it for 3-6 weeks. CFB supplementation decreased insulin levels (Δ3-6 weeks: 1.19 ± 0.65 µ IU/mL → Δ0-3 weeks: -0.58 ± 0.38 µ IU/mL). Increasing degree of fasting blood glucose level was suppressed by intake of CFB, although the suppression was not statistically significant. Except for insulin, there were no significant differences in results of biochemical analysis between 0-3 weeks and 3-6 weeks. Catalase activity was significantly increased by CFB supplementation (Δ3-6 weeks: 3.50 ± 5.30 K g/Hb) compared to the no CFB supplementation period (Δ0-3 weeks: -12.48 ± 4.37 K g/Hb). However, the activity of superoxide dismutase and glutathione-peroxidase were not significantly different between 0-3 weeks and 3-6 weeks. H2O2-induced DNA oxidative damage was also decreased significantly by CFB supplementation. Taken together, these results indicate that CFB has beneficial effect on insulin sensitivity and some antioxidant enzymes in healthy elderly.

Gut Microbiota-Related Cellular and Molecular Mechanisms in the Progression of Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is one of the most common and increasing liver diseases worldwide. NAFLD is a term that involves a variety of conditions such as fatty liver, steatohepatitis, or fibrosis. Gut microbiota and its products have been extensively studied because of a close relation between NAFLD and microbiota in pathogenesis. In the progression of NAFLD, various microbiota-related molecular and cellular mechanisms, including dysbiosis, leaky bowel, endotoxin, bile acids enterohepatic circulation, metabolites, or alcohol-producing microbiota, are involved. Currently, diagnosis and treatment techniques using these mechanisms are being developed. In this review, we will introduce the microbiota-related mechanisms in the progression of NAFLD and future directions will be discussed.