Using Mass Spectrometry Imaging to Visualize Pesticide Accumulation and Time-Dependent Distribution in Fungicide-Coated Seeds.

Pesticide seed treatment provides efficient crop protection in the early season and enables a reduction in the quantity of fungicides used later. Hence, it has been a practical application for crop protection in major crop sectors such as corn, soybean, wheat, and cotton. The chemicals on pesticide-treated seeds may show different distributions depending on the structure of the seeds and the physical properties of the chemicals, but they have not been well studied because of a lack of versatile analytical tools. Here, we used mass spectrometry imaging to visualize the distribution of a fungicide (ethaboxam) in corn and soybean seeds coated with it. Contrasting distribution patterns were noted, which are likely dependent on the seed structure. We also obtained information on fungicide distribution after the seedings, which will contribute to a better understanding of the fungicide delivery pathway within plants. Using this new analytical method, we were able to obtain hitherto unavailable time-dependent, dynamic information on the ethaboxam. We expect that this method will be a useful tool with widespread applications in pesticide development and use. Copyright © 2023 Shuichi Shimma, Hiromi Saito, Takuya Inoue, and Fukumatsu Iwahashi. This is an open-access article distributed under the terms of Creative Commons Attribution Non-Commercial 4.0 International License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Associations of eccentric force variables during jumping and eccentric lower-limb strength with vertical jump performance: A systematic review.

The purpose of this systematic review was to summarize the associations of eccentric force variables during jumping and eccentric lower-limb strength with vertical jump performance. A literature search was conducted in September 2022 using PubMed, Web of Science, and Scopus. Thirteen cross-sectional studies investigating the relationship between eccentric force and strength variables, such as force, rate of force development (RFD), power, time, and velocity, and vertical jump performance, including the jump height, reactive strength index (RSI), and reactive strength index-modified (RSImod), were included in this systematic review. As eccentric strength, variables during the unloading-to-braking phase of countermovement jump (CMJ) (force, RFD, etc.) and the eccentric force of the squat movement and knee joint were included. The CMJ height, RSImod, and drop jump RSI were included to analyze the vertical jump performance. The modified form of the Downs and Black checklist was used to evaluate quality. Associations between the force and RFD during the descending phase of the CMJ and jump height were observed in some studies but not in others, with differences between the studies. Some studies reported associations between the force and/or RFD during the descending phase of the CMJ and RSImod of the CMJ, with no differences among their results. In addition, there are associations of the eccentric forces during squatting and knee extension with the CMJ and the drop jump heights and RSI of the drop jump. The eccentric force variables in the CMJ and RSImod are related; however, their relationship with jump height remains unclear. Furthermore, improved eccentric muscle strength may contribute to vertical jump height because of the associations of the eccentric strength during knee extension and squatting with jump height.

The Validity and Reliability of a Smartphone Application for Break-Point Angle Measurement during Nordic Hamstring Exercise.

Background: A recently developed smartphone application (Nordic Angle) allows the automatic calculation of the break-point angle (BPA) during Nordic hamstring exercise (NHE) without transferring the collected data to a computer. The BPA is the point at which the hamstrings are unable to withstand force. However, the validity of the BPA values obtained by this method has not been examined. Hypothesis/Purpose: This study aimed to evaluate the validity and reliability of the Nordic Angle by comparing the BPA values of the Nordic Angle with those of two-dimensional motion analysis software that can calculate the angles and angular velocities of various joints. Study Design: Cohort assessing Validity and Reliability. Methods: The validity of the Nordic Angle BPA data was verified by Spearman's correlation test for consistency with the movement analysis data, and the magnitude of the correlation was indicated by rs. The agreement between these measurements was examined using the Bland-Altman analysis. The reliability of the Nordic Angle and motion analysis was examined using the intraclass correlation coefficient (ICC) (1,k) based on data from repeated trials within a day. Results: Although the spearman correlation between the Nordic angle and the angle determined using motion analysis did not reach statistical significance (p = 0.052), a very large correlation was present (rs = 0.75). The difference between the mean values of the Nordic Angle and motion analysis was 0.4 ± 2.1°, and the limits of agreement ranged from -3.9° to 4.6°. In two BPA measurements, the Nordic Angle showed perfect reliability (ICC = 1.00, p < 0.001), while motion analysis showed nearly perfect reliability (ICC = 0.97, p < 0.001). Conclusion: The Nordic Angle, which has both validity and reliability, may be appropriate for field measurement because it allows immediate feedback of BPA and the measurement of many athletes. Level of evidence: 3b©The Author(s).

[A case of "colitis-like intestinal Behçet's disease" accompanied by ulcerative colitis after the development of myelodysplastic syndrome].

A 71-year-old man developed ulcerative colitis (UC) at 48 years of age. As a steroid-dependent case with poor UC control, the patient was treated with azathioprine, which resulted in clinical remission. However, a blood test revealed pancytopenia. Bone marrow examination confirmed the diagnosis of myelodysplastic syndrome (MDS). During the patient's clinical course, multiple round ulcers appeared in the terminal ileum. We suspected concomitant "colitis-like intestinal Behçet's disease" (BD). Treatment with adalimumab resolved the ulcers. To the best of our knowledge, this is a rare case of intestinal BD accompanying UC after MDS.

Investigation of the Effect of KIR-HLA Pairs on Hepatocellular Carcinoma in Hepatitis C Virus Cirrhotic Patients.

Natural killer cells are partially mediated through the binding of killer cell immunoglobulin-like receptors (KIR) with human leukocyte antigen (HLA) class I ligands. This investigation examined the risk of hepatocellular carcinoma (HCC) in relation to KIR-HLA pairs in patients with compensated hepatitis C virus (HCV)-associated cirrhosis. A total of 211 Japanese compensated HCV cirrhotic cases were retrospectively enrolled. After KIR, HLA-A, HLA-Bw, and HLA-C typing, associations between HLA, KIR, and KIR-HLA combinations and HCC development were evaluated using the Cox proportional hazards model with the stepwise method. During a median follow-up period of 6.6 years, 69.7% of patients exhibited HCC. The proportions of HLA-Bw4 and the KIR3DL1 + HLA-Bw4 pair were significantly higher in patients with HCC than in those without (78.9% vs. 64.1%; odds ratio (OR)-2.10, 95% confidence interval (CI)-1.10-4.01; p = 0.023 and 76.2% vs. 60.9%, odds ratio-2.05, p = 0.024, respectively). Multivariate analysis revealed the factors of male gender (hazard ratio (HR)-1.56, 95% CI-1.12-2.17; p = 0.009), α-fetoprotein > 5.6 ng/mL (HR-1.56, 95% CI-1.10-2.10; p = 0.011), and KIR3DL1 + HLA-Bw4 (HR-1.69, 95% CI-1.15-2.48; p = 0.007) as independent risk factors for developing HCC. Furthermore, the cumulative incidence of HCC was significantly higher in patients with KIR3DL1 + HLA-Bw4 than in those without (log-rank test; p = 0.013). The above findings suggest KIR3DL1 + HLA-Bw4, in addition to HLA-Bw4, as a novel KIR-HLA pair possibly associated with HCC development in HCV cirrhosis. HCV-associated cirrhotic patients with the risk factors of male gender, α-fetoprotein > 5.6 ng/mL, and KIR3DL1 + HLA-Bw4 may require careful surveillance for HCC onset.

aMAP score prediction of hepatocellular carcinoma occurrence and incidence-free rate after a sustained virologic response in chronic hepatitis C.

AIMS: Hepatocellular carcinoma (HCC) can still occur in hepatitis C virus (HCV) patients who have achieved a sustained virologic response (SVR), which remains an important clinical issue in the direct-acting antivirals era. The current study investigated the clinical utility of the aMAP score (consisting of age, male, albumin-bilirubin, and platelets) for predicting HCC occurrence in HCV patients achieving an SVR by direct-acting antivirals. METHODS: A total of 1113 HCV patients without HCC history, all of whom achieved an SVR, were enrolled for clinical comparisons. RESULTS: Hepatocellular carcinoma was recorded in 50 patients during a median follow-up period of 3.7 years. The aMAP score was significantly higher in the HCC occurrence group than in the HCC-free group (53 vs. 47, p < 0.001). According to risk stratification based on aMAP score, the cumulative incidence of HCC occurrence for the low-, medium-, and high-risk groups was 0.14%, 4.49%, and 9.89%, respectively, at 1 year and 1.56%, 6.87%, and 16.17%, respectively, at 3 years (low vs. medium, low vs. high, and medium vs. high: all p < 0.01). Cox proportional hazard analysis confirmed aMAP ≥ 50 (hazard ratio [HR]: 2.78, p = 0.014), age≥ 70 years (HR: 2.41, p = 0.028), ALT ≥ 17 U/L (HR: 2.14, p < 0.001), and AFP ≥ 10 ng/mL (HR: 2.89, p = 0.005) as independent risk factors of HCC occurrence. Interestingly, all but one patient (99.5%) with aMAP less than 40 was HCC-free following an SVR. CONCLUSION: The aMAP score could have clinical utility for predicting HCC occurrence in HCV patients achieving an SVR.

A Phase II, Multicenter, Randomized, Placebo-Controlled Study of Benralizumab, a Humanized Anti-IL-5R Alpha Monoclonal Antibody, in Patients With Eosinophilic Chronic Rhinosinusitis.

BACKGROUND: Strong eosinophil infiltration in chronic rhinosinusitis with nasal polyp (CRSwNP) is highly associated with recalcitrance and higher nasal polyp recurrence rate after surgery. The prevalence of eosinophilic CRSwNP (ECRS) is increasing in Asian countries including Japan. Benralizumab is a humanized anti-IL-5R alpha monoclonal antibody that depletes eosinophils by antibody-dependent cell-mediated cytotoxicity. OBJECTIVE: To assess the efficacy and safety of benralizumab in patients with ECRS. METHODS: This phase II, randomized, double-blind, placebo-controlled study was conducted in Japan. Patients were randomized 1:2:2 to placebo, a single administration of benralizumab 30 mg, or benralizumab 30 mg every 4 weeks (q4w) for a total of three doses. The primary endpoint was the change in nasal polyp score from baseline at Week 12. RESULTS: Overall, 56 patients were enrolled (placebo, n = 11; benralizumab single dose, n = 22; benralizumab q4w, n = 23). Although the mean total nasal polyp score began to decrease after the initiation of benralizumab treatment, there were no statistically significant differences in change in nasal polyp score from baseline at Week 12 between benralizumab and placebo (placebo, -0.5 ± 0.8; benralizumab single, -0.3 ± 0.8; benralizumab q4w, -0.5 ± 1.5). Post-hoc analysis showed that the administration of benralizumab decreased nasal polyp scores ≥2 points in 42.2% of ECRS patients and that patients with high blood eosinophil levels had a greater tendency to respond to benralizumab treatment. The safety profile was similar to that in previous studies and no unexpected adverse events were noted. CONCLUSION: Although benralizumab did not meet the primary efficacy endpoint, reductions of nasal polyp scores were seen in the benralizumab group compared with the placebo group over the whole study period, especially in patients with high levels of blood eosinophils.

Loss of cell wall integrity genes cpxA and mrcB causes flocculation in Escherichia coli.

Flocculation has been recognized for hundreds of years as an important phenomenon in brewing and wastewater treatment. However, the underlying molecular mechanisms remain elusive. The lack of a distinct phenotype to differentiate between slow-growing mutants and floc-forming mutants prevents the isolation of floc-related gene by conventional mutant screening. To overcome this, we performed a two-step Escherichia coli mutant screen. The initial screen of E. coli for mutants conferring floc production during high salt treatment yielded a mutant containing point mutations in 61 genes. The following screen of the corresponding single-gene mutants identified two genes, mrcB, encoding a peptidoglycan-synthesizing enzyme and cpxA, encoding a histidine kinase of a two-component signal transduction system that contributed to salt tolerance and flocculation prevention. Both single mutants formed flocs during high salt shock, these flocs contained cytosolic proteins. ΔcpxA exhibited decreased growth with increasing floc production and addition of magnesium to ΔcpxA suppressed floc production effectively. In contrast, the growth of ΔmrcB was inconsistent under high salt conditions. In both strains, flocculation was accompanied by the release of membrane vesicles containing inner and outer membrane proteins. Of 25 histidine kinase mutants tested, ΔcpxA produced the highest amount of proteins in floc. Expression of cpxP was up-regulated by high salt in ΔcpxA, suggesting that high salinity and activation of CpxR might promote floc formation. The finding that ΔmrcB or ΔcpxA conferred floc production indicates that cell envelope stress triggered by unfavorable environmental conditions cause the initiation of flocculation in E. coli.

The mechanosensitive channel YbdG from Escherichia coli has a role in adaptation to osmotic up-shock.

Mechanosensitive channels play an important role in the adaptation of cells to hypo-osmotic shock. Among members of this channel family in Escherichia coli, the exact function and physiological role of the mechanosensitive channel homolog YbdG remain unclear. Characterization of YbdG's physiological role has been hampered by its lack of measurable transport activity. Using a nitrosoguanidine mutagenesis-aided screen in combination with next-generation sequencing, here we isolated a mutant with a point mutation in ybdG This mutation (resulting in a I167T change) conferred sensitivity to high osmotic stress, and the mutant cells differed from WT cells in morphology during hyperosmotic stress at alkaline pH. Interestingly, unlike the cells containing the I167T variant, a null-ybdG mutant did not exhibit this sensitivity and phenotype. Although I167T was located near the putative ion-conducting pore in a transmembrane region of YbdG, no change in ion channel activities of YbdG-I167T was detected. Of note, introduction of the WT C-terminal cytosolic region of YbdG into the I167T variant complemented the osmo-sensitive phenotype. Co-precipitation of proteins interacting with the C-terminal YbdG region led to the isolation of HldD and FbaA, whose overexpression in cells containing the YbdG-I167T variant partially rescued the osmo-sensitive phenotype. This study indicates that YbdG functions as a component of a mechanosensing system that transmits signals triggered by external osmotic changes to intracellular factors. The cellular role of YbdG uncovered here goes beyond its predicted function as an ion or solute transport protein.

KIR/HLA genotypes confer susceptibility and progression in patients with autoimmune hepatitis.

Natural killer (NK) cells are key participants in the innate immune response. Killer cell immunoglobulin-like receptors (KIRs) are involved in the activation and inhibition of NK cells through the recognition of human leukocyte antigen (HLA) class I molecules. We investigated the impact of KIR/HLA combinations on susceptibility and long-term clinical outcome in Japanese patients with type 1 autoimmune hepatitis (AIH). METHODS: A total of 154 cases of AIH were recruited at Shinshu University Hospital between 1974 and 2018. KIR genes and HLA class I and II alleles were genotyped in all patients along with 201 healthy individuals. Associations between KIR/HLA pairs and clinical outcomes (liver decompensation and liver-related death) were evaluated using the Cox proportional hazards model with stepwise method. RESULTS: After a median follow-up period of 11.1 years, 12% of patients experienced liver decompensation and 8% died from liver disease. KIR3DL1/HLA-B Bw4-80Ile (p = 0.0062) and the HLA-DRB1*04:05-DQB1*04:01 haplotype (p ≪0.001) were significantly associated with AIH. Conversely, significant protective associations were found for KIR3DL1/HLA-B Bw4-80Thr (p = 0.0092) and KIR2DL1/HLA-C2 (p = 0.0025). The KIR3DL1/HLA-B Bw4-positive phenotype was strongly associated with a favorable clinical outcome (liver decompensation: hazard ratio [HR] 0.37, p = 0.037; liver-related death: HR 0.26, p = 0.038). Cirrhosis was detected in 16 (10%) patients at diagnosis and was significantly related to poor survival (HR 17.87, p ≪0.001) and progression to liver decompensation (HR 9.00, p ≪0.001). CONCLUSIONS: This study revealed the impact of specific KIR/HLA pairs in AIH susceptibility and progression in Japanese patients. KIR3DL1/HLA-B Bw4-negative patients with AIH and cirrhosis at diagnosis are at high risk of adverse outcomes and require careful surveillance. LAY SUMMARY: Autoimmune hepatitis (AIH) is a disease of the liver that can present in acute or chronic hepatitis. We examined whether KIR/HLA pairs were associated with AIH susceptibility or disease progression. KIR3DL1/HLA-B Bw4 was a novel KIR/HLA pair related to a favorable clinical outcome, while cirrhosis at the initial diagnosis was a risk factor for poor prognosis. Thus, frequent and careful surveillance is advised for KIR3DL1/HLA-B Bw4-negative patients with AIH and cirrhosis.

Enhancement of K-strategy evolution in histidine utilization using a container with compartments.

Evolutionary strategies in growth improvement can be classified into r- or K-strategies. The former strategy corresponds to an evolutionary increase in growth rate, whereas the latter corresponds to an increase in the maximum amount of organisms or carrying capacity. What determines the strategies to be adopted during evolution? Spatial structures that compartmentalize the population into small patches are key to inducing the K-strategy. Interestingly, previous evolution experiments using Escherichia coli in a glucose-limited batch culture showed that carrying capacity could improve evolutionally even in the absence of spatial structures. However, it is unclear if the lack of spatial structures can direct evolution toward high carrying capacity for utilization of other resources. To address this question, we established a simplified evolution experiment using histidine-requiring E. coli grown under histidine limitation in a container with compartments. We confirmed the importance of spatial structures in K-strategy evolution in histidine utilization. Whole genome sequencing of the K-adapted strains showed functional variety of the mutated genes during the fitness-increasing period. These results validate the importance of spatial structures and imply that restriction of K-strategy evolution on a sort of nutrients is attributable to a paucity of appropriate selection rather than a paucity of causal mutation.

KIR2DL2 combined with HLA-C1 confers risk of hepatitis C virus-related hepatocellular carcinoma in younger patients.

Killer cell immunoglobulin-like receptors (KIRs) are involved in the activation and inhibition of natural killer cells. Although combinations of KIRs and HLA have been associated with spontaneous and treatment-induced clearance of hepatitis C virus (HCV) infection, their roles are not fully understood in the context of hepatocellular carcinoma (HCC) development. We enrolled 787 consecutive patients with chronic HCV infection, which included 174 cases of HCC, and 325 healthy subjects to clarify the involvement of HLA-Bw and C, KIRs, and major histocompatibility complex class I chain-related gene A (MICA) gene polymorphisms (rs2596542 and rs1051792) in chronic HCV infection and HCV-related HCC. We observed a significant association with chronic hepatitis C susceptibility for HLA-Bw4 (P = 0.00012; odds ratio [OR] = 1.66) and significant protective associations for HLA-C2 and KIR2DL1-HLA-C2 (both P = 0.00099; OR = 0.57). When HCC patients were stratified into younger (<65 years) and older (≥65 years) groups, the frequencies of KIR2DL2-HLA-C1 and KIR2DS2-HLA-C1 (P = 0.008; OR = 2.89 and P = 0.015; OR = 2.79, respectively) as well as rs2596542 and rs1051792 (P = 0.020; OR = 2.17 and P = 0.038; OR = 2.01, respectively) were significantly higher in younger patients. KIR2DL2-HLA-C1 (OR = 2.75; 95% confidence interval: 1.21-6.21, P = 0.015) and rs1051792 (OR = 2.48; 95% confidence interval: 1.23-4.98, P = 0.011) were independently associated with HCC development in younger patients. These results suggest that KIR2DL2-HLA-C1 and rs1051792 may represent molecular biomarkers to identify early onset HCV-related HCC.

Association between KIR-HLA combination and ulcerative colitis and Crohn's disease in a Japanese population.

Inflammatory bowel disease (IBD) consists of ulcerative colitis (UC) and Crohn's disease (CD). Natural killer cell responses play a crucial role in autoimmune disease through innate immunity, in which killer cell immunoglobulin-like receptors (KIRs) are closely involved. Although the genetic combination of KIRs with their specific HLA class I ligands has been associated with IBD in Caucasians, such KIR-HLA receptor-ligand combinations are not fully understood in the Japanese. We investigated 14 KIR genes along with HLA-Bw and -C ligands in 90 patients with UC and 50 patients with CD and compared them with the characteristics of 325 healthy control subjects. The frequency of HLA-Bw4 was significantly increased in patients with UC (P = 1.3 × 10-6; odds ratio [OR] = 3.39) and CD (P = 0.0065; OR = 2.32) versus controls. The UC group had a significantly higher frequency of KIR2DS3 (P = 0.024; OR = 1.94) and lower frequency of KIR2DS4 (P = 0.019; OR = 0.40) and KIR2DL1-HLA-C2 (P = 0.035; OR = 0.47). The Tel-A/B haplotype was significantly decreased in UC patients (P = 0.0056; OR = 0.49). The frequency of KIR3DL1-HLA-Bw4 was significantly higher in patients with UC (P = 4.3 × 10-6; OR = 3.12) and CD (P = 0.0067; OR = 2.30). In conclusion, HLA-Bw4 and KIR-HLA pairs may play an important role in the genetic susceptibility to IBD in the Japanese.

Comparison of the prevalence and characteristics of food hypersensitivity among adolescent and older women.

BACKGROUND AND OBJECTIVES: Although food hypersensitivity is a public health concern, its documentation among the elderly is limited. The current study aims to compare the prevalence and characteristics of food hypersensitivity among adolescent women between aged 18-24 with among older women >50 years of age. METHODS AND STUDY DESIGN: 660 female university students between the ages of 18 and 24 who volunteered were enrolled as adolescent subjects. 470 women >50 years old who visited the Health Care Centre of Kyoto Katsura Hospital for health check-ups were enrolled as the older subjects. A questionnaire created by ourselves asking the presence of food hypersensitivity, symptoms, causative food, personal or family history of other allergic disorders was distributed. RESULTS: The prevalence of food hypersensitivity was statistically similar between adolescent (8.2%) and older women (8.9%). Among them, only 24.1% of the adolescent women and 26.2% of the older women had been diagnosed by physicians as having food allergy. The main causative foods (fruits, shellfish and fish) and the manifestations relating to food hypersensitivity were almost identical between adolescent and older women. In both adolescent and older women, food hypersensitivity positive group showed significantly higher prevalence of personal or family history of allergic disorders than that in food hypersensitivity negative group. CONCLUSIONS: These data indicate that food hypersensitivity in older women should be given more attention because the prevalence of this condition was as common as that in adolescent women.

Increased oxidative stress in patients with severe disability: Association with nutrition.

BACKGROUND: Previous studies have described a role of oxidative stress in the pathogenesis of various pediatric disorders, but investigation into oxidative stress status in patients with severe disability remains limited. The aim of the present study was therefore to clarify the oxidative stress status in patients with severe disability, focusing specifically on intake of three major nutrients and micronutrients with antioxidant activities. METHODS: Thirty-one patients with severe disability (mean age, 14.1 ± 7.8 years) were enrolled. Three in vivo biomarkers, plasma biological antioxidant potential (BAP), plasma reactive oxygen metabolite-derived compounds (d-ROM), and urinary 8-hydroxydeoxyguanosine (8-OHdG), were determined for evaluating oxidative status. The dietary intake of three major nutrients and various micronutrients was estimated from dietary records over a 3 day period. RESULTS: In patients with severe disability, BAP was significantly lower and d-ROM and 8-OHdG significantly higher than in historical controls. Among these markers, a significant positive correlation was found in BAP versus d-ROM and d-ROM versus 8-OHdG. On multiple regression analysis, a significant inverse association between 8-OHdG and carotenoid intake was seen. CONCLUSION: The oxidative/antioxidative balance shifts towards oxidative status dominance in patients with severe disability. More research is needed on nutritional intake of antioxidative nutrients to determine whether they can be used to reduce oxidative stress.

The Ingestion of a Fructose-Containing Beverage Combined with Fat Cream Exacerbates Postprandial Lipidemia in Young Healthy Women.

AIM: To investigate the acute effects of the ingestion of a fructose-containing beverage combinedwith fat on postprandial lipoprotein metabolism. METHODS: Twelve young healthy Japanese women with apolipoprotein E phenotype 3/3 were enrolled in this study. At each of four sessions, the subjects ingested one of four sugar beverages containing fructose and/or glucose (total: 0.5g/kg body weight) combined with OFTT cream (1g/kg, 0.35g/kg as fat) in a randomized crossover design. The four sugar beverages were as follows: 100% (w/w) fructose (F100), 90% fructose+10% glucose (F90G10), 55% fructose+45% glucose (F55G45) and 100% glucose (G100). Venous blood samples were obtained at baseline and 0.5, one, two, four and six hours after ingestion. RESULTS: The serum concentrations of TG in the F100, F90G10 and F55G45 trials were significantlyhigher than each fasting value at two and four hours, and returned to baseline at six hours, except inthe F100 trial. The concentrations at four hours and the incremental areas under the curve for thehepatic triglyceride-rich lipoprotein-triglyceride (VLDL-TG(TM)) levels in the F100 and F90G10 trialswere significantly higher and larger, respectively, than those observed in the G100 trial. Meanwhile,the concentrations of RLP-TG and apolipoprotein B-48 peaked at two hours in the G100 trial, versusfour hours in the other trials, and did not return to baseline at six hours, except in the G100 trial.At four hours, the ⊿apoB48 tended to be higher in the F100 trial than in the G100 trial. CONCLUSIONS: The ingestion of a high-fructose-containing beverage with fat cream delays the clearance of chylomicron and its remnant derived from the intestine and enhances the secretion of triglyceride-rich lipoprotein particles from the liver, thereby inducing postprandial lipidemia, even in young healthy women.

The ingestion of a fructose-containing beverage combined with fat cream exacerbates postprandial lipidemia in young healthy women.

AIM: To investigate the acute effects of the ingestion of a fructose-containing beverage combined with fat on postprandial lipoprotein metabolism. METHODS: Twelve young healthy Japanese women with apolipoprotein E phenotype 3/3 were enrolled in this study. At each of four sessions, the subjects ingested one of four sugar beverages containing fructose and/or glucose (total: 0.5 g/kg body weight) combined with OFTT cream (1 g/kg, 0.35 g/kg as fat) in a randomized crossover design. The four sugar beverages were as follows: 100% (w/w) fructose (F100), 90% fructose + 10% glucose (F90G10), 55% fructose + 45% glucose (F55G45) and 100% glucose (G100). Venous blood samples were obtained at baseline and 0.5, one, two, four and six hours after ingestion. RESULTS: The serum concentrations of TG in the F100, F90G10 and F55G45 trials were significantly higher than each fasting value at two and four hours, and returned to baseline at six hours, except in the F100 trial. The concentrations at four hours and the incremental areas under the curve for the hepatic triglyceride-rich lipoprotein-triglyceride (VLDL-TG(TM)) levels in the F100 and F90G10 trials were significantly higher and larger, respectively, than those observed in the G100 trial. Meanwhile, the concentrations of RLP-TG and apolipoprotein B-48 peaked at two hours in the G100 trial, versus four hours in the other trials, and did not return to baseline at six hours, except in the G100 trial. At four hours, the ⊿apoB48 tended to be higher in the F100 trial than in the G100 trial. CONCLUSIONS: The ingestion of a high-fructose-containing beverage with fat cream delays the clearance of chylomicron and its remnant derived from the intestine and enhances the secretion of triglyceride-rich lipoprotein particles from the liver, thereby inducing postprandial lipidemia, even in young healthy women.

Expression of acidosis-dependent genes in human cancer nests.

Previous studies investigating cancer cells cultured at acidic pH have shown that the expression level of ~700 genes were more than two-fold higher than those of the cells cultured in alkaline medium at pH 7.5. The aim of the present study was to confirm whether these acidosis-induced genes are expressed in human cancer tissues. Therefore, 7 genes were selected from our previous study, which encoded interleukin 32 (IL-32), lysosomal H+ transporting ATPase, V0 subunit d2 (ATP6V0D2), tumor necrosis factor receptor superfamily, member 9 (TNFRSF9), amphiregulin, schwannoma-derived growth factor (AREG), v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (ErbB3), PRR5-ARHGAP8 (LOC553158) and dimethylglycine dehydrogenase (DMGDH), and their expression was examined in human clinical specimens from patients with cancer. In addition, the expression of the gene encoding manganese superoxide dismutase (MnSOD) was examined. The specimens from patients with colon, stomach and renal cancer showed increased MnSOD, IL-32, and TNFRSF9 transcripts compared to those from non-tumorous regions of the same patients. Notably, an elevated expression of ATP6V0D2 was found in the specimens from patients with stomach cancer, whereas the expression was decreased in those from patients with colon and renal cancer. The expression of LOC553158 was upregulated in colon and stomach cancer specimens. These results indicate that the investigation of gene expression under acidic conditions is useful for the development of novel cancer markers and/or chemotherapeutic targets.

Acidic environments enhance the inhibitory effect of statins on proliferation of synovial cells.

Many previous studies in animal models and clinical investigations have suggested that statins are useful chemotherapeutics against rheumatoid arthritis, whereas in vitro experiments using synovial cell lines showed no significant effect of statins on cell proliferation until now. Since synovial fluid in rheumatoid joint knee was found to be acidic, we examined the effect of statins on human synovial sarcoma cell line SW982 cells in acidic medium. Statins suppressed the proliferation of SW982 cells at pH6.7, while the suppression was very weak in pH7.5 medium. It was shown that the suppression was caused by the decrease in geranylgeranyl diphosphate, suggesting that a geranylgeranylated protein(s) has an essential role in cell proliferation of SW982 cells under acidic conditions. Our present data clearly implied that statins had high efficacy against SW982 cells in acidic medium whose pH is close to that of rheumatoid arthritis loci in patients. These results lead us to anticipate that screening of chemicals having high therapeutic efficacy in acidic medium promotes the development of new microenvironment-dependent medicines for chemotherapies against rheumatoid arthritis.

Simultaneous ingestion of fructose and fat exacerbates postprandial exogenous lipidemia in young healthy Japanese women.

AIM: To investigate the acute effects of the simultaneous ingestion of fructose and fat on postprandial lipoprotein metabolism in healthy young women. METHODS: Nine young healthy Japanese women with a normal weight (body mass index: 18.5≤-< 25 kg/m(2)), a normal ovarian cycle and an apolipoprotein E 3/3 phenotype were enrolled as participants and studied on four occasions. At each session, the subjects ingested one of four beverages containing either glucose or fructose (0.5 g/kg body weight each) with or without OFTT cream (1 g/kg, 0.35 g/ kg as fat) in a randomized crossover design. Blood samples were collected at baseline and at 0.5, 1, 2, 4 and 6 hours after ingestion. RESULTS: The ingestion of fructose combined with fat led to significantly higher rises in the serum triglyceride (TG), remnant-like particle (RLP)-TG, remnant lipoprotein-cholesterol (RemL-C) and apolipoprotein B-48 (apoB48) concentrations with delayed peaks compared with that observed following ingestion of the other three types of beverages. The incremental area under the curve (ΔAUC)-TG and ΔAUC-apoB48 were larger than those observed for the ingestion of fat only. The serum RLP-TG and apoB48 concentrations returned to the fasting levels (0 hours) at the end of the test (6 hours) following the ingestion of fat only; however, these concentrations did not return to the fasting levels following the intake of fructose combined with fat. CONCLUSIONS: These findings suggest a delay in the clearance of intestinal TG-rich lipoproteins, namely chylomicron and its remnant, following the ingestion of fructose combined with fat. The simultaneous ingestion of fructose and fat markedly enhances postprandial exogenous lipidemia in young healthy Japanese women.