Journal of Clinical Biochemistry and Nutrition最新文献

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.

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.

We examined the effect of consuming Hoshinishiki, a type of high-amylose rice, on postprandial glucose as measured by continuous glucose monitoring in diabetes patients. A single-blinded 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 test the effects on 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.

The study aimed to explore the impact and potential mechanism of Porphyromonas gingivalis lipopolysaccharide (LPS-PG) on esophageal squamous cell carcinoma (ESCC) cell behavior. ESCC cells from the Shanghai Cell Bank were used, and TLR4, MYD88, and JNK interference vectors were constructed using adenovirus. The cells were divided into six groups: Control, Model, Model + radiotherapy + LPS-PG, Model + radiotherapy + 3-MA, Model + radiotherapy + LPS-PG + 3-MA, and Model + radiotherapy. Various radiation doses were applied to determine the optimal dose, and a radioresistant ESCC cell model was established and verified. CCK8 assay measured cell proliferation, flow cytometry and Hoechst 33258 assay assessed apoptosis, and acridine orange fluorescence staining tested autophagy. Western blot analyzed the expression of LC3II, ATG7, P62, and p-ULK1. Initially, CCK8 and acridine orange fluorescence staining identified optimal LPS-PG intervention conditions. Results revealed that 10 ng/ml LPS-PG for 12 h was optimal. LPS-PG increased autophagy activity, while 3-MA decreased it. LPS-PG + 3-MA group exhibited reduced autophagy. LPS-PG promoted proliferation and autophagy, inhibiting apoptosis in radioresistant ESCCs. LPS-PG regulated TLR4/MYD88/JNK pathway, enhancing ESCC autophagy, proliferation, and radioresistance. In conclusion, LPS-PG, through the TLR4/MYD88/JNK pathway, promotes ESCC proliferation, inhibits apoptosis, and enhances radioresistance by inducing autophagy.

Nucleotide-binding oligomerization domain 2 (NOD2) is an intracellular sensor for muramyl dipeptide (MDP), a degradation product of bacterial cell wall peptidoglycan (PGN). PGN stimulates cell-surface Toll-like receptor 2 (TLR2) independently of NOD2, indicating the presence of crosstalk between extracellular TLR2 and intracellular NOD2 upon exposure to PGN. NOD2-deficient mice were sensitive, while TLR2-deficient mice were resistant to experimental colitis induced by intrarectal administration of PGN. Severe colitis in NOD2-deficient mice was accompanied by increased expression of nuclear factor-kappa B-dependent cytokines and decreased expression of autophagy-related 16-like 1 (ATG16L1). MDP activation of NOD2 enhanced autophagy mediated by TLR2 in human dendritic cells. mRNA expression of TLR2 tended to be higher in the colonic mucosa of patients with active ulcerative colitis compared to that of those in remission. Induction of remission was associated with increased mRNA expression of ATG16L1 in both ulcerative colitis and Crohn's disease patients. Conversely, mRNA expression of receptor-interacting serine/threonine-protein kinase 2 was higher in the inflammatory colonic mucosa of patients with active disease than in the non-inflamed mucosa of patients in remission, in both ulcerative colitis and Crohn's disease. These findings highlight the role of NOD2-TLR2 crosstalk in the immunopathogenesis of colitis.

We have previously reported that chromatin licensing and DNA replication factor 1 (CDT1) is associated with the postoperative recurrence of hepatocellular carcinoma (HCC). Based on this fact, we verified whether CDT1 mRNA expression is also associated with HCC development from chronic hepatitis C (CHC) and liver cirrhosis (LC). There were 142 cases with CHC or LC who underwent liver biopsy. Detection of CDT1 mRNA in liver was performed by RT-qPCR using frozen liver biopsy tissues. We examined the association between the CDT1 mRNA expression and clinical conditions and long-term outcome. We then examined the association between serum cytokine/chemokine levels and CDT1 mRNA expression in 58 cases. The cumulative incidence rates of HCC development in cases with CDT1 mRNA in the low expression group showed significantly lower than those in the high expression group (p = 0.0391). A significant correlation was found between CDT1 mRNA expression and the extent of proliferation of atypical hepatocytes in hematoxylin and eosin-stained sections (p<0.0001). CDT1 mRNA expression has been associated with cytokines involved in tumorigenesis in experimental and human cancers. We found that cases with high CDT1 mRNA expression were at risk for developing HCC, even if they were CHC or LC.

Transcription is regulated by specific transcription factors that mediate signaling in response to extrinsic and intrinsic stimuli such as nutrients, hormones, and oxidative stresses. Many transcription factors are grouped based on their highly conserved DNA binding domains. Consequently, transcription factors within the same family often exhibit functional redundancy and compensation. NRF2 (NFE2L2) and NRF1 (NFE2L1) belong to the CNC family transcription factors, which are responsible for various stress responses. Although their DNA binding properties are strikingly similar, NRF2 and NRF1 are recognized to play distinct roles in a cell by mediating responses to oxidative stress and proteotoxic stress, respectively. In this review, we here overview the distinct and shared roles of NRF2 and NRF1 in the transcriptional regulation of target genes, with a particular focus on the nuclear protein binding partners associated with each factor.

We conducted a retrospective case-control study to assess the efficacy of personalized health guidance interventions on individuals with type 2 diabetes mellitus and obesity. A selection was made of individuals in regular visits to the Takagi Hospital for medical checkups between January 2017, and October 2021. Totally, 108 subjects (cases) with health guidance were divided into 2 groups: one group without pharmacotherapy for diabetes mellitus in medical institutions (n = 92) and another group with pharmacotherapy (n = 116). Cases were provided with personalized health guidance interventions by public health nurses for 30 min, in accordance with the Japanese clinical guidelines for the prevention of lifestyle-related diseases. Sex- and age-matched controls were chosen from individuals with diabetes mellitus without health guidance. The intervention without pharmacotherapy resulted in improvements in health indicators, including body weight, waist circumference, diastolic blood pressure, triglyceride levels, and γ-glutamyl trans-peptidase. These positive effects were not observed in the control group without health guidance. The therapeutic effects of health guidance were observed in cases where pharmacotherapy was administered. In conclusion, the implementation of individual health guidance interventions may prove to be effective for individuals with type 2 diabetes mellitus and obesity who regularly attend medical checkups.

[This corrects the article DOI: 10.3164/jcbn.22-105.].

Reactive oxygen species (ROS) and highly reactive oxygen species (hROS) secreted by leukocytes are crucial to innate immunity; however, they pose a risk of oxidative stress. To monitor their balance in daily health check-ups, optical technologies for the simultaneous measurement of ROS (superoxide radicals) and hROS (hypochlorite ions) that utilize only a few microliters of whole blood have been developed. The aim of this study was to clarify whether this system could assess the effects of fat ingestion on postprandial oxidative status. Eight healthy young Japanese women ingested a beverage containing oral fat tolerance test cream. Blood samples were collected before and 0.5, 1, 2, 4, and 6 h after fat ingestion. Blood ROS and hROS levels, oxidative stress markers, and biochemical markers were monitored. Consistent with previous studies, triglyceride levels significantly increased at 4 h (p<0.01) and returned to near-baseline levels 6 h after ingestion. ROS levels peaked significantly at 2 h (p<0.05), and hROS levels peaked significantly at 1 (p<0.05) and 2 h (p<0.01) after ingestion. This study offers an insight into the acute effects of fat ingestion on leukocyte activity and provides a methodology for monitoring postprandial oxidative status.