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Abstract 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

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.

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.

Objective: Previous studies have separately reported the contributions of dietary factors to the risk of cardiovascular disease (CVD) and its markers, including blood pressure (BP) and lipid profile. This study systematically reviewed the current evidence on this issue in the Korean population. Methods: Sixty-two studies from PubMed and Embase were included in this meta-analysis. We performed a random-effects model to analyze pooled odds ratios (ORs) and hazard ratios (HRs) and their 95% confidence intervals (CIs) for the consumption of 14 food items, three macro- and eight micro-nutrients, two dietary patterns, and three dietary indices. Results: An analysis of pooled effect sizes from at least four individual study populations showed significant associations between coffee consumption and CVD (OR/HR, 0.71; 95% CI, 0.52–0.97) and elevated/high triglycerides (TG) (OR, 0.84; 95% CI, 0.78–0.90), sugarsweetened beverage intake and elevated BP (OR/HR, 1.20; 95% CI, 1.09–1.33), and milk and dairy intake and elevated/high TG and low high-density lipoprotein cholesterol (HDL-C) (OR/HR, 0.82; 95% CI, 0.76–0.89 for both). Carbohydrate consumption and the lowcarbohydrate-diet score were consistently related to an approximately 25% risk reduction for elevated TG and low HDL-C. A lower risk of elevated total cholesterol, but not low-density lipoprotein, was additionally observed for those with a higher low-carbohydrate-diet score. A healthy dietary pattern was only associated with a reduced risk of elevated TG in the Korea National Cancer Screenee Cohort (OR, 0.81; 95% CI, 0.67–0.98). Conclusion: This study showed that milk and dairy and coffee had protective effects for CVD and its risk factors, such as BP and lipid profile, while sugar-sweetened beverages exerted harmful effects.

PURPOSE: The purpose of this study was to investigate the effects of thermotherapy on gas pain, post-operative resilience, and body temperature discomfort among patients who received laparoscopic myomectomies. METHODS: The experimental group consisted of 62 patients with thermotherapy and the control group consisted of 60 patients. Thermotherapy was applied individually to the experimental group four hours after surgery. The collected data was analyzed using descriptive statistics, t-tests, χ²-tests, and repeated measures of analysis of variance, using IBM SPSS Statistics version 18. RESULTS: The results showed no significant interaction effect between the group and time of measurement in gas-related pain in the experimental group. For gas-related pain, there was significant difference in right shoulder pain at 24 hours (t=-4.222, p=.000), 48 hours (t=-3.688, p=.000), 72 hours (t=-2.250, p=.028), and left at 24 hours (t=-3.727, p=.000), 48 hours (t=-4.150, p=.000), and 72 hours (t=-2.482, p=.016) and both shoulders at 24 hours (t=-2.722, p=.009) and 48 hours (t=-2.525, p=.014). There was no significant difference in epigastric pain, excluding both epigastric pain at 48 hours (t=2.908, p=.005), 72 hours (t=3.010, p=.004), but there was a significant difference in objective body temperature discomfort (t=2.895, p=.008). CONCLUSION: Thermotherapy relieved shoulder gas-related pain and objective body temperature discomfort. It needs to be developed and applied to improve post-operative discomfort in patients with laparoscopic hysterectomies.

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 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.

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.

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.

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.

In chronic liver disease, the causative factor is important; however, recently, the intestinal microbiome has been associated with the progression of chronic liver disease and the occurrence of side effects. The immune system is affected by the metabolites of the microbiome, and diet is the primary regulator of the microbiota composition and function in the gut–liver axis. These metabolites can be used as therapeutic material, and postbiotics, in the future, can increase or decrease human immunity by modulating inflammation and immune reactions. Therefore, the excessive intake of nutrients and the lack of nutrition have important effects on immunity and inflammation. Evidence has been published indicating that microbiome-induced chronic inflammation and the consequent immune dysregulation affect the development of chronic liver disease. In this research paper, we discuss the overall trend of microbiome-derived substances related to immunity and the future research directions.

Efforts to enhance thermal efficiency of turbines by increasing the turbine inlet temperature have been further accelerated by the introduction of 3D printing to turbine components as complex cooling geometry can be implemented using this technique. However, as opposed to the properties of materials fabricated by conventional methods, the properties of materials manufactured by 3D printing are not isotropic. In this study, we analyzed the anisotropic thermal conductivity of nickel-based superalloy CM247LC manufactured by selective laser melting (SLM). We found that as the density decreases, so does the thermal conductivity. In addition, the anisotropy in thermal conductivity is more pronounced at lower densities. It was confirmed that the samples manufactured with low energy density have the same electron thermal conductivity with respect to the orientation, but the lattice thermal conductivity was about 16.5% higher in the in-plane direction than in the cross-plane direction. This difference in anisotropic lattice thermal conductivity is proportional to the difference in square root of elastic modulus. We found that ellipsoidal pores contributed to a direction-dependent elastic modulus, resulting in anisotropy in thermal conductivity. The results of this study should be beneficial not only for designing next-generation gas turbines, but also for any system produced by 3D printing.

Many biological studies involve either (i) manipulating some aspect of a cell or its environment and then simultaneously measuring the effect on thousands of genes, or (ii) systematically manipulating each gene and then measuring the effect on some response of interest. A common challenge that arises in these studies is to explain how genes identified as relevant in the given experiment are organized into a subnetwork that accounts for the response of interest. The task of inferring a subnetwork is typically dependent on the information available in publicly available, structured databases, which suffer from incompleteness. However, a wealth of potentially relevant information resides in the scientific literature, such as information about genes associated with certain concepts of interest, as well as interactions that occur among various biological entities. We contend that by exploiting this information, we can improve the explanatory power and accuracy of subnetwork inference in multiple applications. Here we propose and investigate several ways in which information extracted from the scientific literature can be used to augment subnetwork inference. We show that we can use literature-extracted information to (i) augment the set of entities identified as being relevant in a subnetwork inference task, (ii) augment the set of interactions used in the process, and (iii) support targeted browsing of a large inferred subnetwork by identifying entities and interactions that are closely related to concepts of interest. We use this approach to uncover the pathways involved in interactions between a virus and a host cell, and the pathways that are regulated by a transcription factor associated with breast cancer. Our experimental results demonstrate that these approaches can provide more accurate and more interpretable subnetworks. Integer program code, background network data, and pathfinding code are available at https://github.com/Craven-Biostat-Lab/subnetwork_inference.

The purpose of this study was to evaluate the immune-enhancing effect of red gamju fermented with Levilactobacillus brevis KU15154, isolated from kimchi, as a biofunctional beverage using mice. Thirty-two mice were used, and after a 2-week feeding, the growth, cytokine and immunoglobulin production, and immune-related cell activation (phagocytes and natural killer [NK] cells) of the mice were evaluated. The red gamju- (SR) and fermented red gamju- (FSR) treated groups had 3.5–4.0-fold greater T-cell proliferation ability than the negative control group. IFN-γ production in the FSR group (15.5 ± 1.2 mg/mL) was significantly higher (p < 0.05) than that in the SR group (12.5 ± 1.8 mg/mL). The FSR group (502.6 ± 25.8 μg/mL) also showed higher IgG production levels than the SR group (412.2 ± 44.8 μg/mL). The activity of NK cells treated with FSR was also greater than that of cells treated with SR but it was not significant (p ≤ 0.05). Further, the phagocytic activity of peritoneal macrophages was higher in both SR and FSR groups than in the control group but was not significantly different (p < 0.05) between the SR and FSR groups. In conclusion, L. brevis KU15154 may be applied in the fermentation of bioactive food products, such as beverages or pharmaceutical industries, to potentially improve immunity.

Statins and omega-3 supplementation have shown potential benefits in preventing cardiovascular disease (CVD), but their comparative effects on mortality outcomes, in addition to primary and secondary prevention and mixed population, have not been investigated. This study aimed to examine the effect of statins and omega-3 supplementation and indirectly compare the effects of statin use and omega-3 fatty acids on all-cause mortality and CVD death. We included randomized controlled trials (RCTs) from meta-analyses published until December 2019. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated to indirectly compare the effect of statin use versus omega-3 supplementation in a frequentist network meta-analysis. In total, 55 RCTs were included in the final analysis. Compared with placebo, statins were significantly associated with a decreased the risk of all-cause mortality (RR = 0.90, 95% CI = 0.86–0.94) and CVD death (RR = 0.86, 95% CI = 0.80–0.92), while omega-3 supplementation showed a borderline effect on all-cause mortality (RR = 0.97, 95% CI = 0.94–1.01) but were significantly associated with a reduced risk of CVD death (RR = 0.92, 95% CI = 0.87–0.98) in the meta-analysis. The network meta-analysis found that all-cause mortality was significantly different between statin use and omega-3 supplementation for overall population (RR = 0.91, 95% CI = 0.85–0.98), but borderline for primary prevention and mixed population and nonsignificant for secondary prevention. Furthermore, there were borderline differences between statin use and omega-3 supplementation in CVD death in the total population (RR = 0.92, 95% CI = 0.82–1.04) and primary prevention (RR = 0.85, 95% CI = 0.68–1.05), but nonsignificant differences in secondary prevention (RR = 0.97, 95% CI = 0.66–1.43) and mixed population (RR = 0.92, 95% CI = 0.75–1.14). To summarize, statin use might be associated with a lower risk of all-cause mortality than omega-3 supplementation. Future direct comparisons between statin use and omega-3 supplementation are required to confirm the findings.

The authors found a language error in the published article. The authors replace the Figure 1.

Ultraviolet B (UVB) irradiation causes adverse effects on the skin. Corn silk contains flavonoids and other bioactive compounds and antioxidants, which may prevent skin photoaging through antioxidant and anti-inflammatory effects. We aimed to investigate the potential photoprotective effects of dietary corn silk on UVB-induced skin damage in mice and the mechanisms behind these effects on human skin cells. Oral administration of corn silk water extract (CS) (2 or 4 g/kg/day) for 19 weeks decreased epidermal thickness, wrinkle formation, and positive staining for PCNA, Ki67, and 8-OHdG, and increased collagen staining in UVB-irradiated SKH-1 hairless mice compared with controls. The pro-inflammatory NF-κB target genes (IL-1β, iNOS, and COX-2) and MMP-9 expressions were lower in the CS groups, and TGF-β/Smad signaling increased. Low skin lipid peroxidation and blood DNA oxidation levels and high blood glutathione were detected. Antioxidant transcription factor Nrf2-related catalase and SOD1 proteins and glutaredoxin mRNA levels increased. The results of CS extract treatment and UVB irradiation in HaCaT cells showed the same results in Nrf2 and NF-κB target genes. An LC-MS/MS analysis showed that the CS extract contained potential antioxidants, which might have contributed to its anti-photoaging effects in tissues and cells. CS extract may reduce UVB-induced skin damage through antioxidant and anti-inflammatory mechanisms.

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 noninvasive 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 Seoul National University Bundang 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 noninvasive tool for monitoring the efficacy of surgery in PTC. [ABSTRACT FROM AUTHOR]