Photodynamic therapy (PDT) is useful for various cancers such as high-grade glioma and cancers of other organs. However, the mechanism of tumor-specific accumulation of porphyrin is not clear. The authors previously reported that heme carrier protein 1 (HCP1) contributes to the transport of porphyrins; specifically, we ‍showed that the production of cancer-specific reactive oxygen ‍species from mitochondria (mitROS) leads in turn to enhanced ‍HCP1 expression. Indomethacin (IND), a non-steroidal anti-inflammatory drug, increases ROS production by affecting mitochondrial electron transfer system. In the present work, the authors investigated the effect of pretreatment with IND on cancer-specific porphyrin accumulation, using both a glioma cell line and a rat brain tumor model. This work demonstrated that exposure of a rat glioma cell to IND results in increased generation of cancer-specific mitROS and accumulation of HCP1 expression and porphyrin concentration. Additionally, systemic dosing of a brain tumor animal model with IND resulted in elevated cellular accumulation of porphyrin in tumor cell. This is ‍an effect not seen with normal brain tissue. Thus, the administration of IND increases intracellular porphyrin concen­trations in tumor cell without exerting harmful effects on normal brain tissue, and increased porphyrin concentration in tumor cell may lead to improved PDT effect.

Observational studies have suggested a relationship between antioxidants and birth weight (BW). However, the causal association remains unclear. The aim of this study was to assess the causal relationship between antioxidants and BW. Genome wide association study (GWAS) summary statistics for 4 endogenous and 7 exogenous antioxidants, as well as BW were obtained from GWAS studies and UK biobank. A two-sample Mendelian randomization (MR) analysis was conducted with fixed-effects model inverse variance weighted (IVW) as the primary analytical method, while MR Egger and weighted median used as auxiliary. A series of sensitivity analyses were conducted to verify the robustness of the results. The MR results revealed that genetically predicted higher superoxide dismutase (SOD, β = 0.025; 95% CI: 0.008, 0.043; P = 0.005) and zinc (β = 0.030; 95% CI: 0.013, 0.047; P = 0.001) levels were significantly associated with higher BW. Sensitivity analysis verified the robustness of the MR results. Our study reinforced the existing evidence supporting a significant positive association between SOD and zinc with BW, providing new genetic evidence for antioxidant supplementation during pregnancy to prevent low BW infants. Further deeper comprehension studies are warranted to confirm these findings.

To maintain the oxygen supply, the production of red blood cells ‍(erythrocytes) is promoted under low-oxygen conditions (hypoxia). Oxygen is carried by hemoglobin in erythrocytes, in which the majority of the essential element iron in the body is contained. Because iron metabolism is strictly controlled in a semi-closed recycling system to protect cells from oxidative stress ‍caused by iron, hypoxia-inducible erythropoiesis is closely coordinated by regulatory systems that mobilize stored iron for hemoglobin synthesis. The erythroid growth factor erythropoietin (EPO) is mainly secreted by interstitial fibroblasts in the renal cortex, which are known as renal EPO-producing (REP) cells, and ‍promotes erythropoiesis and iron mobilization. Intriguingly, EPO production is strongly induced by hypoxia through iron-dependent pathways in REP cells. Here, we summarize recent studies on the network mechanisms linking hypoxia-inducible EPO production, erythropoiesis and iron metabolism. Additionally, we introduce disease mechanisms related to disorders in the network mediated by REP cell functions. Furthermore, we propose future studies regarding the application of renal cells derived from the urine of kidney disease patients to investigate the molecular pathology of chronic kidney disease and develop precise and personalized medicine for kidney disease.

In the present study, the authors examined the association between gastric bacterial infection and gastric endoscopic findings in H. pylori-negative patients. The subjects were 105 H. pylori-negative patients. The mean age was 72.8 ± 9.1 years. Endoscopy and gastric juice culture were performed. The presence or absence of endoscopic findings was checked according to the Kyoto classification of gastritis. Results: Culture was positive in 69 patients (65.7%), with Streptococcus α-hemolytic being the most common (51 patients), followed by Neisseria sp. (43 patients). According to the univariate analysis, there was a significant difference between the results of culture and background factors in the use of gastric antisecretory drugs and between the results of culture and various endoscopic findings in atrophic gastritis, intestinal metaplasia, RAC, mucosal swelling, sticky mucus, hyperplastic polyps, hematin, and gastric cobblestone-like lesions. Furthermore, multivariate analysis revealed significant differences in background factors such as the use of gastric antisecretory drugs and endoscopic findings only in patients with mucosal swelling. Endoscopic findings of non-H. pylori bacteria-positive gastritis differed from endoscopic findings of H. pylori-infected gastritis in several respects. Conclusion: Our results suggest that non-H. pylori bacteria may infect the stomach and cause gastric inflammation, especially in patients who use gastric antisecretory drugs.

Copper (Cu), an essential micronutrient, participates in several physiological processes, including cell proliferation and development. Notably, the disturbance of Cu homeostasis promotes tumor progression through the generation of oxidative stress. Chronic or excessive accumulation of reactive oxygen species (ROS) causes lipid peroxidation, protein denaturation, and enzyme inactivation, which leads to a breakdown of intracellular homeostasis and exacerbates tumor progression. The disruption of the ROS scavenging mechanism also reduces resistance to oxidative stress, leading to further deterioration in a disease state, and maintenance of redox homeostasis is thought to inhibit the onset and progression of various diseases. Superoxide dismutase 3 (SOD3), a Cu-containing secretory antioxidative enzyme, plays a key role in extracellular redox regulation, and the significant reduction in SOD3 facilitates tumor progression. Furthermore, the significant induction of SOD3 participates in tumor metastasis. This review focuses on the role of Cu homeostasis and antioxidative enzymes, including SOD3, in tumor progression, to help clarify the role of redox regulation.

Sirtuin 3 involved in development of various diseases, but its role ‍in inflammatory bowel disease is still unknown. We used inflammatory bowel disease biopsies, colitis animal model, and vitro cells RAW264.7 to study the role of Sirtuin 3 in the pathophysiology of inflammatory bowel disease. Sirtuin 3 negatively correlated with intestinal TNF-α. Sirt3 was less pronounced in pediatric and adult inflammatory bowel disease patients compared with corresponding control group. Sirtuin 3 activator Honokiol suppressed dextran sulfate sodium induced colonic manifestations, while Sirt3 inhibitor caused opposite results. Honokiol inhibited colonic oxidative stress by and reduced ‍intestinal permeability. Honokiol repressed inflammatory response by reducing macrophage infiltration, pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 levels, and inhibiting activation of NF-κB p65 in the colitis mice. However, Sirt3 inhibitor amplified colonic oxidative stress and inflammatory response. In vitro study, ‍Sirt3 inhibitor or siRNA Sirtuin 3 activated NF-κB p65 and enhanced TNF-α, IL-1β, and IL-6 secretion from LPS stimulated RAW264.7, while Honokiol remarkably attenuated these pro-inflammatory cytokines secretion. Finally, knockdown of Sirt3 in Caco-2 cells enhanced TNF-α induced intestinal barrier integrity injury. Sirtuin 3 negatively regulates inflammatory bowel disease progression via reducing colonic inflammation and oxidative stress. Sirtuin 3 is a promising therapeutic target in clinical application for inflammatory bowel disease therapy.

Sphingolipids have recently gained interest as potential players in variety of diseases due to their import roles in human body particularly, the brain. As sphingomyelin is the most common type of sphingolipids, deficits in its distribution to brain cells may contribute to neurological anomalies. However, data is limited regarding the impact of different levels of dietary sphingomyelin intake on neural function especially if this approach can boost cognition and prevent neurological disorders. This review evaluates the effect of dietary sphingomyelin and its metabolites (ceramide and sphingosine-1-phosphate) in animal models and in humans, with a primary focus on its impact on brain health. Additionally, it proposes multiple neuroenhancing effects of sphingomyelin-rich diet. This presents an opportunity to stimulate further research that aims to determine the therapeutic value of dietary sphingomyelin in preventing, improving or slowing the progression of central nervous system disorders.

The prevalence of chronic kidney disease (CKD) is increasing owing to the elderly population. Here, we investigated the effects of heat-treated Enterococcus faecalis (FK-23) and lysozyme-treated FK-23 (LFK) on the progression of CKD in rats. A CKD model was established using male Wistar rats by subjecting them to right nephrectomy (1K), followed by ischemia and reperfusion (IR). FK-23 or LFK was fed ad libitum as a mixed diet after right nephrectomy. Animals subjected to renal ischemia-reperfusion injury (IRI) showed increased plasma creatinine and blood urea nitrogen levels. Furthermore, in the kidneys, collagen accumulation and α-smooth muscle actin, indicative of fibroblast activation and fibrosis-related gene and protein expression, increased 3 weeks after IRI. FK-23 and LFK suppressed the increase in the mRNA levels of some of these genes. The increase in oxidative stress markers, 4-hydroxy-2-nonenal, endothelial nitric oxide synthase, and nitrotyrosine in the kidney, as well as increased plasma uremic toxins after IRI, were also ameliorated by FK-23 and LFK. Metagenomic analysis of fecal samples revealed that gut microbial alteration caused by IRI was also ameliorated by LFK treatment. These results suggest that E. faecalis ingredients may improve CKD progression by suppressing oxidative stress and correcting the balance of the intestinal microflora.

Background: Mitophagy is a cellular survival mechanism that is indispensable in carcinogenesis and tumor progression. However, the research on the mechanism of mitophagy in esophageal cancer metastasis is limited. This study explored the regulatory mechanism by which RECQL4 regulates mitophagy and affects esophageal cancer metastasis.

Methods: The RECQL4 expression in esophageal cancer tissues was examined by bioinformatics analysis and validated by qRT-PCR. Bioinformatics analysis was used to determine the upstream regulatory factor of RECQL4, CREB1, and find the correlation between them. Their binding relationship was evaluated using dual luciferase assay and Chromatin Immunoprecipitation (ChIP) assay. The role of RECQL4 in the viability and metastasis of esophageal cancer cells was investigated through experiments including CCK-8, Transwell, and immunofluorescence. GFP-LC3 plasmid was transfected into cells, followed by western blot (WB) to detect the expression of autophagy marker proteins LC3Ⅰ, LC3Ⅱ, and p62 to analyze mitophagy.

Results: The expression of RECQL4 was up-regulated in esophageal cancer tissues and cells. Overexpression of RECQL4 promoted the viability, invasion, migration, and epithelial-mesenchymal transition (EMT) of esophageal cancer cells by inhibiting mitophagy. Bioinformatics analysis found a substantial positive correlation between the expression of RECQL4 and its upstream transcription factor, CREB1, followed by validation of their binding relationship using dual luciferase and ChIP assays. CREB1 knockdown promoted mitophagy and prevented the metastasis of cancer cells, which could be countered by overexpressing RECQL4.

Conclusion: In this study, CREB1 was found to transcriptionally activate RECQL4 to inhibit mitophagy, thereby promoting esophageal cancer metastasis. This suggests that targeting mitophagy could be an effective therapeutic approach for esophageal cancer.

The endosomal–lysosomal system represents a crucial degradation pathway for various extracellular substances, and its dysfunction is linked to cardiovascular and neurodegenerative diseases. This degradation process involves multiple steps: (1) the uptake of extracellular molecules, (2) transport of cargos to lysosomes, and (3) digestion by lysosomal enzymes. While cellular uptake and lysosomal function are reportedly regulated by the mTORC1–TFEB axis, the key regulatory signal for cargo transport remains unclear. Notably, our previous study discovered that isorhamnetin, a dietary flavonoid, enhances endosomal–lysosomal proteolysis in the J774.1 cell line independently of the mTORC1–TFEB axis. This finding suggests the involvement of another signal in the mechanism of isorhamnetin. This study analyzes the molecular mechanism of isorhamnetin using transcriptome analysis and reveals that the transcription factor GATA3 plays a critical role in enhanced endosomal–lysosomal degradation. Our data also demonstrate that mTORC2 regulates GATA3 nuclear translocation, and the mTORC2–GATA3 axis alters endosomal formation and maturation, facilitating the efficient transport of cargos to lysosomes. This study suggests that the mTORC2–GATA3 axis might be a novel target for the degradation of abnormal substances.

We used standardized detection ratio to evaluate the quality of nasal upper gastrointestinal endoscopy screening for the secondary prevention of gastric cancer, and examined the gastric cancer risk in the era of total H. pylori eradication. We performed 21,931 upper gastrointestinal endoscopies, 77 subjects were diagnosed with gastric cancer. Of these, 28 had gastric cancer after H. pylori eradication, 47 had gastric cancer with H. pylori-positive or others, and 2 had H. pylori-negative gastric cancer. The Standardized detection ratios for men and women were 5.33 and 4.82, respectively. Multivariable logistic regression analyses performed exclusively on first endoscopy subjects, excluding H. pylori-negative gastric cancer, revealed that smoking was a risk factor for developing gastric cancer (adjusted odds ratio, 3.31; 95% confidence interval, 1.65–6.64; P = 0.001). A statistically significant interaction was found between daily alcohol consumption and H. pylori eradication on gastric cancer development (P = 0.005). In conclusion, relatively high standardized detection ratio values suggest that an appropriate endoscopic diagnosis of gastric cancer should be performed during a medical check-up. Smoking is a risk factor for developing gastric cancer, and continued alcohol consumption suggests a possible risk for developing gastric cancer after H. pylori eradication.

Caveolae, consisting of caveolin-1 proteins, are ubiquitously present in endothelial cells and contribute to normal cardiovascular functions by acting as a platform for cellular signaling pathways as well as transcytosis and endocytosis. However, caveolin-1 is thought to have a proatherogenic role by inhibiting endothelial nitric oxide synthase activity and Nrf2 activation, or by promoting inflammation through NF-κB activation. Dietary polyphenols were suggested to exert anti-atherosclerotic effects by a mechanism involving the inhibition of endothelial dysfunction, by which they can regulate redox-sensitive signaling pathways in relation to NF-κB and Nrf2 activation. Some monomeric polyphenols and microbiota-derived catabolites from monomeric polyphenols or polymeric tannins might be responsible for the inhibition, because they can be transferred into the circulation from the digestive tract. Several polyphenols were reported to modulate caveolin-1 expression or its localization in caveolae. Therefore, we hypothesized that circulating polyphenols affect caveolae functions by altering its structure leading to the release of caveolin-1 from caveolae, and attenuating redox-sensitive signaling pathway-dependent caveolin-1 overexpression. Further studies using circulating polyphenols at a physiologically relevant level are necessary to clarify the mechanism of action of dietary polyphenols targeting caveolae and caveolin-1.

Borderline low-density lipoprotein cholesterol (LDL-C) levels (120-139 mg/dL) increase the risk of cardiovascular disease. Therefore, the use of functional dietary nutrients is expected to control blood LDL-C levels. This study aimed to evaluate the effect of dietary secoisolariciresinol diglucoside (SDG) on blood cholesterol in healthy adults with borderline LDL-C levels. A randomized, parallel, controlled, double-blinded clinical trial was performed for participants with borderline LDL-C levels, for 12 weeks with SDG (60 mg/day) or placebo. Lipid profile [LDL-C, high-density lipoprotein cholesterol (HDL-C), LDL-C/HDL-C ratio, total cholesterol (TC), and triglycerides] and liver disease risk markers were measured at weeks 0, 4, 8, and 12. Analyzing 36 participants in each group revealed a significant interaction between treatment and time, indicating reduced LDL-C (p = 0.049) and TC (p = 0.020) levels in SDG-receiving men but not women. However, no significant differences were observed in other markers regardless of gender. The results suggest that a daily intake of 60 mg of SDG lowers LDL-C and TC levels in men with borderline LDL-C, proposing SDG's potential as a functional dietary nutrient for cardiovascular disease prevention. This study was registered in the UMIN-CTR database (UMIN000046202).

Neutrophil extracellular trap (NET) formation is a unique self-defense mechanism of neutrophils; however, it is also involved in many diseases, including atherosclerosis. Resveratrol and catechin are antioxidants with anti-atherosclerotic properties. Here, we examined the effects of resveratrol, catechin, and other related compounds on NET formation. HL-60-derived neutrophils were pretreated with resveratrol and other compounds before stimulation with phorbol-myristate acetate (PMA). DNA and myeloperoxidase (MPO) released from neutrophils were determined. Resveratrol suppressed the DNA release from neutrophils in a dose-dependent manner. NET formation was enhanced in the presence of 1-palimitoyl-2-oxovaleroyl phosphatidylcholine, a truncated form of oxidized phospholipid, and resveratrol suppressed NET formation induced by the oxidized phospholipid and PMA. Furthermore, we designed several analogs of resveratrol or catechin whose conformation was restricted by the inhibition of the free rotation of aromatic rings. The conformationally constrained analogs were more effective at inhibiting NET formation; however, their inhibitory function decreased when compound was a large, hydrophobic analog. The most potent compounds, planar catechin and resveratrol, suppressed MPO release from activated neutrophils. In addition, these compounds suppressed DNA release from neutrophils stimulated with calcium ionophore. These results suggest that resveratrol, catechin and their analogs exert anti-NET effects, and that constraining the geometry of these compounds enhanced their inhibitory effects.

In this study, we investigated the relationship between the cecal intubation time (CIT) and the form and method used for passing through the sigmoid/descending colon junction (SDJ) and the hepatic flexure using an endoscopic position detection unit (UPD), with reference to various factors [age, sex, body mass index (BMI), history of abdominal and pelvic surgery, and diverticulum]. A total of 152 patients underwent colonoscopy with UPD. The mean age was 66.9 ‍± 12.4 years, and the male to female ratio was ‍3.6:1. The average CIT time was 14.3 ‍± 8.2 ‍min. Age, number of experienced endoscopies, history of abdominal and pelvic surgery, BMI, and diverticulum were associated with prolonged CIT; SDJ passage pattern was straight: 8.6 ‍± 5.0, alpha loop: 11.8 ‍± 5.6, puzzle ring-like loop: 20.2 ‍± 5.0, reverse alpha loop: 22.4 ‍± 9.7, and other loop: 24.7 ‍± 10.5. The hepatic flexure passing method was in the following order: right rotation maneuver: 12.6 ‍± 6.6, push maneuver: 15.1 ‍± 5.9, and right rotation with positional change maneuver: 20.5 ‍± 7.2. In conclusion, colonoscopy with UPD revealed an association between CIT and SDJ passage pattern and hepatic flexure passing method.

Types of fats and oils affect the onset of lifestyle diseases. In this study, we investigated the relationship between the postprandial hyperglycemia and fatty acids content in the skeletal muscle of C57BL/6 mice given 20% lard, palm oil, corn oil, safflower oil, and flaxseed oil for 16 weeks. Lard increased plasma glucose and insulin levels at the end of feeding period, whereas flaxseed oil did not. It was noteworthy that there is a positive correlation between palmitic acid content in the muscle and postprandial hyperglycemia, and a negative correlation between α-linolenic acid content and hyperglycemia. Alternatively, mice were given 30% lard for 16 weeks. When lard was partially substituted with flaxseed oil (10-50% substitution), flaxseed oil dose-dependently prevented lard-induced hyperglycemia and hyperinsulinemia. In conclusion, flaxseed oil prevents the adverse effects of lard through increasing in α-linolenic acid content in the muscle.

Gastrointestinal bleeding (GIB) is a significant public health concern, predominantly associated with high morbidity. However, there have been no reports investigating the trends of GIB in Japan using nationwide data. This study aims to identify current trends and issues in the management of GIB by assessing Japan’s national data. We analyzed National Database sampling data from 2012 to 2019, evaluating annual hospitalization rates for major six types of GIB including hemorrhagic gastric ulcers, duodenal ulcers, esophageal variceal bleeding, colonic diverticular bleeding, ischemic colitis, and rectal ulcers. In this study, hospitalization rates per 100,000 indicated a marked decline in hemorrhagic gastric ulcers, approximately two-thirds from 41.5 to 27.9, whereas rates for colonic diverticular bleeding more than doubled, escalating from 15.1 to 34.0. Ischemic colitis rates increased 1.6 times, from 20.8 to 34.9. In 2017, the hospitalization rate per 100,000 for colonic diverticular bleeding and ischemic colitis surpassed those for hemorrhagic gastric ulcers (31.1, 31.3, and 31.0, respectively). No significant changes were observed for duodenal ulcers, esophageal variceal bleeding, or rectal ulcers. The findings of this study underscore a pivotal shift in hospitalization frequencies from upper GIB to lower GIB in 2017, indicating a potential shift in clinical focus and resource allocation.

Abstract: Hepatocellular carcinoma (HCC) has high fatality and poor prognosis. For curing HCC, the demand for effective therapeutic reagents with low toxicity is urgent. Herein, we investigated plasma-activated medium (PAM), a emerging reagent obtained via irradiation of cell-free medium with cold atmospheric plasma (CAP). PAM exerts inhibitory effect on many types of tumor cells with little toxicity to non-cancerous cells. In present study, we verified the tumor-specific inhibition of HCC cell lines Huh-7 and HepG2 by PAM. Under the PAM-effect, oxidative stress and mitochondrial dysfunction were detected inside cells. Meanwhile, the loss of intracellular NAD and ATP were ob-served, suggesting a energy depletion. Through investigating the salvage pathway which synthesizes NAD⁺ and maintains the normal proceeding of respiratory chain in HCC, we found that the energy failure was resulted by PAM-induced blockage of the salvage pathway. Moreover, nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in the salvage pathway, was determined as an important target to be inactivated by PAM-effect. Additionally, the blockage of the salvage pathway activates AMPKα and suppresses mTOR pathway, which reinforces the cell growth inhibition. Taken together, our findings demonstrated that the interference with functions of NAMPT and the sal-vage pathway contribute to the tumor-specific cytotoxicity of PAM.

Growth hormone (GH) exerts multiple effects on different organs directly or via its main mediator, insulin-like growth factor1 (IGF1). In this study, we focused on the novel relationship between GH action and the antiaging hormone α-klotho. Immunofluorescent staining of α-klotho was observed in the renal distal tubules and pituitary glands of somatostatin- and GH-positive cells in wild-type (WT) mice. Treatment of 4-week-old WT mice with GH increased IGF1 mRNA expression in the pituitary gland, liver, heart, kidney, and bone but increased α-klotho mRNA expression only in the pituitary gland, kidney, and bone. Increased α-klotho protein levels were observed in the kidney but not in the pituitary gland. No induction of α-klotho RNA expression by GH was observed in juvenile mice with kidney disease, indicating GH resistance. Furthermore, GH and α-klotho supplementation in HEK293 cells transfected with GHR increased Janus kinase 2 mRNA (a GH downstream signal) expression compared to supplementation with GH alone. In conclusion, we suggest that 1) the kidney is the main source of secreted α-klotho, which is detected in blood by the downstream action of GH, 2) α-klotho induction by GH is resistant in kidney disease, and 3) α-klotho might be an enhanced regulator of GH signaling.

Background: Previous researches have revealed the potential association between dietary niacin intakes and several diseases, but studies assessing the association between dietary niacin intakes and nonalcoholic fatty liver disease (NAFLD) is limited and remains unclear. This study was performed to explore the association.

Methods: In this study, 10,528 participants (male: 5,257) in the 10 NHANES cycles (1999-2018) from the NHANES database were selected for the analyses. We built three logistic regression models to explore the independent association between dietary niacin intakes and NAFLD and to explore whether such association exists. Finally, a restricted cubic spline model was applied to simulate the potential nonlinear association between dietary niacin intakes and the occurrence of NAFLD.

Results: The result of the fully-adjusted model suggested that ln-transformed dietary niacin intakes were significantly associated with the reduced occurrence of NAFLD. The Odd ratio (OR) of the model and its 95% confidence interval (CI) were 0.81 (0.73, 0.90). When taking the lowest quartile as a reference, the level of niacin in the highest quartile was associated with decreased prevalence of NAFLD (OR: 0.76, 95% CI: 0.63, 0.91). The restricted cubic spline plot presented a negative dose-response association between levels of daily niacin consumption and the occurrence of NAFLD (p for nonlinearity = 0.762).

Conclusion: According to the results of this study, dietary niacin intakes may have a negative association with NAFLD, and more well-designed cohort studies are required in the future to confirm the obtained finding.

We examined the effect of consuming Hoshinishiki, a type of high-amylose rice produced in Ehime Prefecture (Japan), on postprandial glucose as measured by continuous glucose monitoring in patients with diabetes. A single-blinded and randomized clinical trial involving 11 hospitalized patients diagnosed with type 1 or type 2 diabetes was performed. The patients consumed high-amylose rice for 2 days (days 2 and 4 of the study) and control rice for 2 days (days 1 and 3 of the study). Linear mixed models were used to analyze the 24-h mean glucose levels, time in range (TIR), incremental area under the curve of glucose levels at 2 h after meals, the average glucose levels at 1, 2, and 3 h after meals, and the maximum glucose levels within 3 h. The results showed that the consumption of high-amylose rice led to significantly lower 24-h mean glucose levels, , levels at 2 and 3 h after a meal, and postprandial glucose peak levels within 3 h, as well as significantly higher TIR. A similar trend was observed when the analysis was restricted to patients with type 2 diabetes. These results suggest that high-amylose rice may be a more beneficial staple food for glycemic control than regular rice.

Neutrophils express protein arginine deiminase (PAD)2 and PAD4, both of which mediate the citrullination of target proteins to induce production of neutrophil extracellular traps (NETs). Although PAD-dependent NETs trigger inflammatory bowel disease, the mechanisms governing the expression of PAD2 and PAD4 are poorly understood. In this study, we tried to clarify expression mechanisms of PAD2 and PAD4 in the colonic mucosa of patients with ulcerative colitis (UC) and Crohn’s disease (CD). Administration of Cl-amidine, a pan PAD-inhibitor, attenuated the development of dextran sodium sulfate-induced colitis, the effects of which were accompanied by reduced IL-6 and TNF-α production by colonic lamina propria mononuclear cells upon exposure to Toll-like receptor ligands. The mRNA expression of colonic PAD2 and PAD4 was negatively and positively correlated with disease activity and pro-inflammatory cytokine responses in patients with UC, respectively. Reciprocal regulation of PAD2 and PAD4 mRNA expression was observed in the colonic mucosa of UC patients, but not in those of CD patients. PAD4 mRNA expression was correlated with disease activity and pro-inflammatory cytokine responses in patients with CD. Collectively, these data suggest that reciprocal regulation of PAD2 and PAD4 expression is associated with disease activity in UC patients.

Photoreceptor degeneration decreases light sensitivity and leads to vision loss and various retinal diseases. Neurotrophin-3, originating from Müller glial cells in the retina, plays a key role in protecting photoreceptors from damage induced by light or hypoxia. This neuroprotective approach is important because there are no established methods to regenerate lost photoreceptors. Dietary supplements are one of the useful methods for improving eye health. Eurycoma longifolia Jack, which is native to the tropical forest of Malaysia and other Southeast Asian countries, exhibits several medicinal properties. In the present study, we demonstrated that the water extract of E. longifolia roots enhanced neurotrophin-3 gene expression in primary rat Müller cells. Using a stepwise bioassay-guided fractionation and purification of E. longifolia root extracts, we isolated the active compound underlying neurotrophin-3 gene-enhancing activities. Mass spectrometry and nuclear magnetic resonance spectral data identified the compound as eurycomanone. This study provides evidence for the efficacy of E. longifolia and eurycomanone in enhancing neurotrophin-3 expression in Müller cells in vitro. Although the biological significance of this effect and its underlying mechanism remain to be elucidated, this study suggests that E. longifolia may be promising for improving eye health and must be further investigated.

Objective: To investigate the effect and potential mechanism of porphyromonas gingivalis lipopolysaccharide (LPS-PG) on esophageal squamous cell carcinoma (ESCC) cell proliferation, apoptosis, and autophagy.

Materials and methods: ESCCs were obtained from the Shanghai Cell Bank, Chinese Academy of Sciences. Adenovirus was used to construct TLR4, MYD88 and JNK interference vectors and cells were randomly divided into six groups: Control, Model, Model+radiotherapy+LPS-PG, Model+radiotherapy+3-MA, Model+radiotherapy+LPS-PG+3-MA, and Model+radiotherapy group. Different doses of radiation were used to intervene ESCC to determine the optimal radiation dose, and the acquired radioresistant esophageal squamous cell carcinoma cell model was constructed, and the model was verified by clonal formation experiment. CCK8 assay was used to detect cell proliferation, flow cytometry and Hoechst 33258 assay were used to detect cell apoptosis, acridine orange fluorescene staining was used to test cell autophagy. Expression of LC3II，ATG7，P62 and p-ULK1 were measured by western blot.

Results: Firstly, CCK8 and acridine orange fluorescene staining were used to detect the autophagy and proliferation ability of ESCC cells, respectively. According to the activation degree and proliferation ability of autophagy, the optimal intervention concentration and action time of LPS-PG were screened. The results showed that the optimal intervention concentration of LPS-PG was 10 ng/ml and the action time was 12 h. Then we observed the effect of LPS-PG on autophagy in ESCC. Compared with the control group, the autophagy activity of cells in the LPS-PG group was significantly increased, the expression levels of LC3II and ATG7 were significantly increased, the autophagy activity of cells in the 3-MA group was decreased, and the expression levels of p62 and p-ULK1 were significantly increased. Compared with LPS-PG group, autophagy in LPS-PG+3-MA group decreased, LC3II and ATG7 expression decreased, and p62 and p-ULK1 expression increased. Then we observed the effects of LPS-PG on the proliferation, apoptosis and autophagy of acquired radioresistent ESCCs. The results showed that LPS-PG could promote the proliferation and autophagy of acquired radioresistance ESCCs, and inhibit its cell apoptosis. Finally, we tested the effect of LPS-PG on TLR4/MYD88/JNK pathway to clarify its potential mechanism. The results showed that LPS-PG could not only regulate the autophagy activation of ESCCs through TLR4/MYD88/JNK pathway, but also promote the proliferation and autophagy of acquired radioresistance ESCCs and inhibit its cell apoptosis by regulating TLR4/MYD88/JNK pathway.

Conclusion: LPS-PG can promote cell proliferation, inhibit cell apoptosis, promote autophagy and thus promote cell radioresistance of ESCC by regulating the TLR4/MYD88/JNK pathway.

Macrophages produce many inflammatory mediators, such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), in innate immune responses. However, excess production of these mediators by activated macrophages triggers deleterious effects, leading to disorders associated with inflammation. Royal jelly (RJ), a milky-white substance secreted by worker bees, contains unique fatty acids, including 10-hydroxy-2-decenoic acid (10H2DA) and sebacic acid (SA). 10H2DA has been reported to have various biological functions, such as anti-inflammation. However, the anti-inflammatory effect of SA is not fully understood. In this study, we investigated the effects of SA on lipopolysaccharide (LPS)-induced cytokine expression using differentiated human THP-1 macrophage-like cells. SA dose-dependently decreased LPS-induced mRNA expression of IL-6, but not TNF-α and IL-1β. SA suppressed the phosphorylation of signal transducers and activators of transcription 1 (STAT1) and STAT3, but hardly affected the activation of JNK, p38, or NF-κB. In addition, SA decreased LPS-induced interferon-β (IFN-β) expression, and the addition of IFN-β restored the inhibition by SA of LPS-induced STAT activation and IL-6 expression. Furthermore, SA suppressed LPS-induced nuclear translocation of interferon regulatory factor 3 (IRF3), a transcription factor responsible for IFN-β expression. Taken together, we conclude that SA selectively decreases LPS-induced expression of IL-6 mRNA through inhibition of the IRF3/IFN-β/STAT axis.

The amounts of Reactive oxygen species (ROS) become higher by strenuous exercises which consume larger amounts of oxygen in active muscles. Since these ROS directly injured muscles, the high ROS concentration involves muscle fatigue. Thus, an immediate ROS scavenging system in the muscle is desired. Since Monascus pigment (MP) involves physiologically active substances which scavenge ROS, it may be a clue to save the muscle injury. However, there are no reports examining MP effects on oxidative stress in skeletal muscle. In this study, we investigated the effect and mechanism of MP on skeletal muscle cells damaged by oxidative stress. The ability to directly eliminate ROS was evaluated by mixing MP solutions with ^・OH and O₂^・−, a type of ROS. The effect of peroxidation in C2C12 cells was evaluated by cell viability assay or western blotting. MP scavenges ^・OH and O₂^・−. MP treatment increases the survival rate under oxidative stress. At that time, the expression of catalase, an antioxidant enzyme, was increased: the enzyme change H₂O₂ into H₂O to rescue the cells under oxidative stress. We conclude that monascus pigment suppressed myotube damage under oxidative stress by both non-enzymatic ROS scavenging and up-regulation of catalase expression.