Prebiotic inulin ameliorates SARS-CoV-2 infection in hamsters by modulating the gut microbiome.

Current treatment options for COVID-19 are limited, with many antivirals and immunomodulators restricted to the most severe cases and preventative care limited to vaccination. As the SARS-CoV-2 virus and its increasing variants threaten to become a permanent fixture of our lives, this new reality necessitates the development of cost-effective and accessible treatment options for COVID-19. Studies have shown that there are correlations between the gut microbiome and severity of COVID-19, especially with regards to production of physiologically beneficial short-chain fatty acids (SCFAs) by gut microbes. In this study, we used a Syrian hamster model to study how dietary consumption of the prebiotic inulin affected morbidity and mortality resulting from SARS-CoV-2 infection. After two weeks of observation, we discovered that inulin supplementation attenuated morbid weight loss and increased survival rate in hamster subjects. An analysis of microbiome community structure showed significant alterations in 15 genera. Notably, there were also small increases in fecal DCA and a significant increase in serum DCA, perhaps highlighting a role for this secondary bile acid in conferring protection against SARS-CoV-2. In light of these results, inulin and other prebiotics are promising targets for future investigation as preventative treatment options for COVID-19.

Complete genome sequences of Bifidobacterium faecale strain JCM19861T, isolated from human feces.

Here, we report the complete genome sequence of the Bifidobacterium faecale strain JCM 19861T (= CU 3-7T = KACC 17904T), isolated from infant feces by Jung-Hye Choi's group in 2014. The B. faecale JCM 19861T genome comprised a circular chromosome of 2,213,206 bp, with a G + C content of 59.0%.

Combined effects of BARLEYmax and cocoa polyphenols on colonic microbiota and bacterial metabolites in vitro.

BARLEYmax, a barley variety, and cocoa polyphenols (CPPs) have been reported to affect bacterial metabolites in the colon. This study aimed to evaluate the combined effects of BARLEYmax and CPPs supplementation on fecal microbiota in vitro using pig feces for 48 h. The relative abundances of the family Clostridiaceae and the genus Clostridium and ammonia-nitrogen production were decreased by both BARLEYmax and CPP supplementation, and there was a positive correlation between their abundances and the ammonia-nitrogen concentration. Although acetate and n-butyrate production was decreased by CPP supplementation, their concentrations were maintained at a higher level in the BARLEYmax + CPP group than in the cellulose (control) and cellulose + CPP groups. Therefore, this study demonstrated that a combination of BARLEYmax and CPPs may be beneficial in maintaining higher short-chain fatty acid production and the elimination of potentially harmful factors. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10068-021-00959-z.

Deciphering the colonic fermentation characteristics of agavin and digestion-resistant maltodextrin in a simulated batch fermentation system.

Gut microbial fermentation of soluble dietary fibers promotes general and substrate-specific health benefits. In this study, the fermentation characteristics of two soluble branched-dietary fibers, namely, agavin (a type of agave fructans) and digestion-resistant maltodextrin (RD) were investigated against cellulose, using a simulated colonic fermenter apparatus employing a mixed culture of swine fecal bacteria. After 48 h of complete fermentation period, the microbial composition was different among all groups, where Bifidobacterium spp. and Lactobacillus spp. dominated the agavin treatment, while the members of the families Lachnospiraceae and Prevotellaceae dominated the RD treatment. Agavin treatment exhibited a clearly segregated two-phased prolonged fermentation trend compared to RD treatment as manifested by the fermentation rates. Further, the highest short-chain fatty acids production even at the end of the fermentation cycle, acidic pH, and the negligible concentration of ammonia accumulation demonstrated favorable fermentation attributes of agavin compared to RD. Therefore, agavin might be an effective and desirable substrate for the colonic microbiota than RD with reference to the expressed microbial taxa and fermentation attributes. This study revealed a notable significance of the structural differences of fermentable fibers on the subsequent fermentation characteristics.

Comparison of the prebiotic properties of native chicory and synthetic inulins using swine fecal cultures.

Inulin-type fructans are known to exert different effects on the fermentation profile depending on the average and range of the degree of polymerization (DP). Here, swine fecal cultures were used to investigate the prebiotic properties of native chicory inulin (NIN), extracted from the chicory root, and synthetic inulin (SIN), which has a narrower DP distribution than NIN. Both NIN and SIN showed prebiotic effects, but NIN exhibited a significant decrease in pH and increase in the production of propionate and butyrate compared to SIN. There were also differences in the production of succinate and lactate, the precursors of propionate and butyrate, and the relative abundance of associated genes. Furthermore, NIN induced the growth of certain species of Bifidobacterium and Lactobacillus more strongly than SIN. These results suggest that NIN and SIN exhibit different prebiotic properties due to differences in DP, and that NIN might be more beneficial to host health.

Effects of BARLEYmax and high-ß-glucan barley line on short-chain fatty acids production and microbiota from the cecum to the distal colon in rats.

We investigated whether supplementation with the barley line BARLEYmax (Tantangara; BM), which contains three fermentable fibers (fructan, ß-glucan, and resistant starch), modifies the microbiota in cecal and distal colonic digesta in addition to short-chain fatty acids (SCFAs) production more favorably than supplementation with a high-ß-glucan barley line (BG012; BG). Male Sprague-Dawley rats were randomly divided into 3 groups that were fed an AIN-93G-based diet that contained 5% fiber provided by cellulose (control), BM or BG. Four weeks after starting the respective diets, the animals were sacrificed and digesta from the cecum, proximal colon and distal colon were collected and the SCFA concentrations were quantified. Microbiota in the cecal and distal colonic digesta were analyzed by 16S rRNA sequencing. The concentrations of acetate and n-butyrate in cecal digesta were significantly higher in the BM and BG groups than in the control group, whereas the concentration of total SCFAs in cecal digesta was significantly higher only in the BM group than in the control group. The concentrations of acetate and total SCFAs in the distal colonic digesta were significantly higher only in the BM group than in the control group. The abundance of Bacteroidetes in cecal digesta was significantly higher in the BM group than in the control group. In contrast, the abundance of Firmicutes in cecal digesta was significantly lower in the BM and BG groups than in the control group. These results indicated that BM increased the concentration of total SCFAs in the distal colonic digesta. These changes might have been caused by fructan and resistant starch in addition to ß-glucan. In conclusion, fermentable fibers in BM reached the distal colon and modified the microbiota, leading to an increase in the concentration of total SCFAs in the distal colonic digesta, more effectively compared with the high-ß-glucan barley line (BG).

QT dispersion and prognosis after coronary stent placement in acute myocardial infarction.

BACKGROUND: QT dispersion is increased in acute myocardial infarction (AMI), but the relation of QT dispersion to prognosis has not yet been fully elucidated. HYPOTHESIS: The purpose of this study is to evaluate prospectively whether QT dispersion is associated with the risk of major adverse cardiac events (MACEs) and mortality after successful coronary stenting in AMI. METHODS: One hundred and forty-two patients with AMI and undergoing successful percutaneous coronary intervention (PCI) were enrolled in this study. Corrected QT dispersion was measured before and 24 h after PCI. RESULTS: During a period of 4477 person-months, we confirmed 21 cases of MACE. Univariate analysis indicated that corrected QT dispersion before and 24 h after PCI, age, number of Q waves, and Killip class > or = 2 were related to MACE and mortality. By multivariate analysis, corrected QT dispersion before PCI was an independent predictor of MACE and mortality, but corrected QT dispersion at 24 h after PCI was not statistically associated with MACE and mortality. Multiple-adjusted hazard ratios for a 1 standard deviation (SD) magnitude increase in corrected QT dispersion before PCI were 2.24 (95% confidence interval, 1.36-3.68, p = 0.001) for MACE and 2.71 (95% confidence interval, 1.50-4.89, >) for mortality after adjustment for age, gender, ejection fraction, and Killip class > or = 2. CONCLUSIONS: Corrected QT dispersion before PCI is associated with an increased risk of MACE and mortality after successful PCI in patients with AMI.

Inflection point of ascending aortic waveform is a predictive factor for major adverse cardiac events after successful coronary stent placement in acute myocardial infarction.

OBJECTIVE: The reflection waveform in the ascending aortic pressure has been reported to reflect systemic arterial stiffness, and increase the risk of coronary heart disease. The purpose of this study is to evaluate prospectively whether the reflection waveform in the ascending aortic pressure is associated with the risk of major adverse cardiac events (MACE) after successful coronary stenting in acute myocardial infarction (AMI). METHODS AND RESULTS: One hundred and twenty-five patients with AMI and undergoing successful coronary stenting were enrolled in this study. We measured the inflection time to determine the reflection waveform in the ascending aortic pressure at angioplasty. Inflection time was defined as the time interval from initiation of a systolic pressure waveform to the inflection point. During a period of 2945 person-months, we confirmed 42 cases of MACE. Shorter inflection time increased incident MACE. Kaplan-Meier analysis demonstrated a significantly reduced event-free rate in patients with inflection time < or = 86 ms (MACE; p < 0.01, cardiovascular death; p < 0.001 by log-rank test). The multiple-adjusted hazard ratio for a I standard deviation (SD) magnitude decrease in inflection time was 1.46 (95% confidence interval, 1.03 to 2.05) for MACE, and 5.76 (95% confidence interval, 1.78 to 18.67) for cardiovascular death. CONCLUSIONS: Shorter inflection time increased the risk of MACE after successful coronary stenting in patients with AMI.

QT dispersion and left ventricular function after stent placement in acute myocardial infarction.

BACKGROUND: QT dispersion is increased in acute myocardial infarction (AMI), but the relation of QT dispersion to left ventricular (LV) function has not yet been fully elucidated. The purpose of this study was to evaluate the relationship between QT dispersion and LV function in patients with successful coronary stenting in AMI. METHODS: Seventy five patients with AMI who underwent percutaneous transluminal coronary angioplasty (PTCA) were enrolled in this study. Corrected QT dispersion was measured before, immediately after, 24 h after, 48 h after, and 6 months after PTCA. Left ventricular ejection fraction (LVEF) was evaluated by left ventriculography at 6 months after PTCA. RESULTS: Corrected QT dispersion at 24 h after and 48 h after PTCA were significantly related to LVEF by univariate analysis (r=-0.282, p<0.05 and r=-0.326, p<0.01, respectively). In multiple regression model, corrected QT dispersion at 24 h after and 48 h after PTCA revealed significant associations with LVEF (R(2)=0.441, coefficient=-0.283, p=0.006 and R(2)=0.411, coefficient=-0.225, p=0.039, respectively), but corrected QT dispersion before, immediately after, and 6 months after PTCA were not associated with LVEF. CONCLUSIONS: Corrected QT dispersion at 24 h after and 48 h after PTCA in AMI correlate with LVEF at 6 months after PTCA.

Inflection point of ascending aortic waveform is a predictive factor for all-cause and cardiovascular mortality in patients with chronic renal failure on hemodialysis.

BACKGROUND: The reflection waveform in the ascending aortic pressure has been reported to reflect systemic arterial stiffness, and increase risk of coronary heart disease. The purpose of this study is to evaluate prospectively whether the reflection waveform in the ascending aortic pressure is associated with the mortality in patients with chronic renal failure on hemodialysis. METHODS: Fifty two patients with chronic renal failure on hemodialysis and undergoing cardiac catheterizations were enrolled in this study. Inflection time was measured to determine the reflection waveform in the ascending aortic pressure at angiography. Inflection time was defined as the time interval from initiation of a systolic pressure waveform to the inflection point. RESULTS: The mean duration of follow-up was 55 +/- 49 months (mean +/- SD). Mean age at entry was 58.5 +/- 9.0 years. We confirmed 14 cardiovascular deaths, and 5 non-cardiovascular deaths. Shorter inflection time increased all-cause and cardiovascular mortality. Kaplan-Meier analysis demonstrated a significantly reduced survival ratio in patients with inflection time < or =87 msec (all-cause death; P < 0.01, cardiovascular death; P < 0.001 by log-rank test). Multiple-adjusted hazard ratio for 10 msec decrease in inflection time was 1.49 (95% confidence interval, 1.07 to 2.08) for all-cause mortality, and was 4.66 (95% confidence interval, 1.82 to 11.95) for cardiovascular mortality. CONCLUSION: Shorter inflection time increased all-cause and cardiovascular mortality in patients with chronic renal failure on hemodialysis.

The timing of the reflected wave in the ascending aortic pressure predicts restenosis after coronary stent placement.

It has been reported that the reflection waveform in the ascending aortic pressure is associated with systemic arterial stiffness. Stiffening of the aortic walls leads to a decrease in coronary perfusion and an increase in restenosis rate. The purpose of this study was to evaluate whether the reflection waveform in the ascending aortic pressure could be used to predict restenosis after percutaneous coronary stenting. One hundred and three patients who underwent percutaneous coronary stenting were enrolled in this study. We measured the inflection time and augmentation index (AIx) to determine the reflection waveform in the ascending aortic pressure at angioplasty. We then prospectively investigated the effect of inflection time and AIx in relation to the subsequent risk of restenosis after coronary stenting. After adjustments for age, gender, smoking habits, hypertension, type 2 diabetes, hypercholesterolemia, stent size, and heart rate, the odds ratio of restenosis in inflection time was 4.62 (95% confidence interval (CI), 1.39 to 15.4) for the lowest tertile of the inflection time level compared with the highest tertile level. As for AIx, the odds ratio of restenosis was 6.96 (95% CI, 1.93 to 25.1) for the highest tertile of the AIx level compared with the lowest tertile level. Inflection time and AIx are related to restenosis after percutaneous coronary stenting.

Intravenous nicorandil can reduce QT dispersion and prevent bradyarrhythmia during percutaneous transluminal coronary angioplasty of the right coronary artery.

BACKGROUND: Nicorandil, a potassium channel opener, is used for the treatment of angina pectoris and has a pharmacologic preconditioning effect. This study evaluated whether intravenous nicorandil reduces QT dispersion and prevents bradyarrhythmia during percutaneous transluminal coronary angioplasty (PTCA) of the right coronary artery. METHODS: A historical cohort study on the effect of nicorandil on QT dispersion and bradyarrhythmia was conducted. Fifty patients who underwent PTCA of the right coronary artery were enrolled. The patients were divided into a nicorandil (n = 25) group and control group (n = 25). Nicorandil was injected at 4 mg/h continuously 1 hour before PTCA in the nicorandil group. QT dispersion was measured at 1 hour before PTCA (baseline), immediately before PTCA, and 1 minute after the initiation of the first balloon inflation. RESULTS: QT dispersion at 1 minute after the initiation of the first balloon inflation in the control group increased significantly (QT dispersion: 37.1 +/- 17.8 msec and 21.7 +/- 12.2 msec, respectively, P < .001 vs baseline in the control group), and this was larger than at 1 minute after the initiation of the first balloon inflation in the nicorandil group (QT dispersion: 37.1 +/- 17.8 msec and 20.8 +/- 9.4 msec, respectively, P < .001). By two-way repeated measures analysis of variance, there were significant interactions between the time factor and the grouping factor in QT dispersion (P < .001). Bradyarrhythmia was observed in 6 patients in the control group, but none was observed in the nicorandil group. CONCLUSIONS: Intravenous nicorandil reduces QT dispersion and prevents bradyarrhythmia during PTCA of the right coronary artery.

Anti-inflammatory effects of tacalcitol (1,24(R)(OH)2D3, TV-02) in the skin of TPA-treated hairless mice.

Tacalcitol (1,24(R)(OH)2D3, TV-02) inhibited the TPA-induced inflammatory cell infiltration (largely neutrophils) histopathologically and myeloperoxidase (MPO) activity dose-dependently. Tacalcitol inhibited the mRNA expression and protein production of TPA-induced macrophage inflammatory protein-2 (MIP-2) and KC, the functional analogue of human interleukin (IL)-8, in the skin. Immunohistochemical staining of the TPA-applied skin revealed that mast cells expressed MIP-2, whereas KC was observed in keratinocytes, fibroblasts and outer root sheath of hair follicles. Furthermore, tacalcitol inhibited TPA-induced mast cell degranulation 24 hr after application without influence on the total number of mast cells. In this study, tacalcitol was found to have an inhibitory effect on cutaneous inflammation such as inhibition of neutrophil infiltration, MIP-2 and KC production, and mast cell degranulation in TPA-treated hairless mice. These results suggest that tacalcitol modulates cutaneous inflammation as well as keratinocyte proliferation and differentiation, and the inhibitory effect of tacalcitol on cutaneous inflammation may contribute to clinical the effectiveness in the treatment of psoriasis.

Intravenous nicorandil can reduce the occurrence of ventricular fibrillation and QT dispersion in patients with successful coronary angioplasty in acute myocardial infarction.

BACKGROUND: Because nicorandil, a potassium channel opener, has a cardioprotective effect and attenuates reperfusion injury in patients with acute myocardial infarction (AMI), intravenous nicorandil should reduce arrhythmic mortality and QT dispersion in patients with AMI. OBJECTIVES: The purpose of this study was to evaluate whether intravenous nicorandil reduces the occurrence of ventricular fibrillation and QT dispersion in patients with successful coronary angioplasty in AMI. METHODS: A historical cohort study on the effect of nicorandil on ventricular fibrillation and QT dispersion was conducted. Eighty-three patients with AMI who underwent successful percutaneous transluminal coronary angioplasty (PTCA) were enrolled. The patients were divided into two groups: nicorandil (n=46) and control group (n=37). Nicorandil was injected at 4 mg/h continuously from admission to 48 h after PTCA in the nicorandil group. QT dispersion was measured before, immediately after, 24 h after and 48 h after PTCA. RESULTS: Ventricular fibrillation was observed in three patients in the control group, but none was observed in the nicorandil group. QT dispersion in the nicorandil group was shorter than that in the control group 48 h after PTCA (QT dispersion was 23.2+/-16.1 ms and 33.4+/-24.0 ms, respectively, P<0.05). There was a significant difference between the two groups in time course after the onset of AMI (P<0.05). CONCLUSIONS: Because intravenous nicorandil reduces the occurrence of ventricular fibrillation and QT dispersion in patients with successful coronary angioplasty in AMI, it would prevent the occurrence of cardiac events after successful PTCA for AMI.

Thrombus formation after aortic valvular replacement using Björk-Shiley valve occluding the right coronary orifice.

We describe a patient with unstable angina due to occlusion of the orifice of the right coronary artery by thrombus formation after aortic valvular replacement using a Björk-Shiley valve. After strict anticoagulant treatment, transesophageal echocardiography demonstrated disappearance of the thrombus formation around the orifice of the right coronary artery.

Fusiform coronary aneurysm in the left circumflex artery with recurrent myocardial infarction and idiopathic thrombopenia.

The authors describe the rare case of a patient with fusiform coronary aneurysm with myocardial infarction in the left circumflex artery complicated by idiopathic thrombopenia. Medical treatment with a combination of warfarin and aspirin could not prevent recurrence of angina pectoris and myocardial infarction, but surgical ligation of the proximal site of the fusiform aneurysm and coronary bypass to the distal site of the fusiform aneurysm prevented further myocardial infarction and angina pectoris.

Human neutrophils express messenger RNA of vitamin D receptor and respond to 1alpha,25-dihydroxyvitamin D3.

1Alpha,25-Dihydroxyvitamin D3 (1,25(OH)2D3) has been shown to modulate the production of various cytokines or the expression of certain differentiation markers in human T cells or monocytes. Its effects on neutrophils, however, are poorly understood. In this paper, we show several lines of evidence indicating that neutrophils express functional vitamin D receptors (VDR). Sort-purified neutrophils from human peripheral blood expressed VDR mRNA at a level comparable to that of monocytes. As reported to occur in monocytes, protein expression of CD14 on the cell surface of neutrophils was augmented when the cells were incubated with 1,25(OH)2D3. To investigate the physiological roles for VDR in neutrophils, we investigated possible modulating effects of 1,25(OH)2D3 on the expression of several genes in lipopolysaccharide-stimulated neutrophils by using differential display analysis. Of the genes we identified, trappin-2/elafin/SKALP, which was originally reported to be an inhibitor of elastase, was induced in neutrophils by lipopolysaccharide, but was suppressed significantly in the presence of 1,25(OH)2D3. Under the same conditions, interleukin-1beta expression was also inhibited. These findings suggest that 1,25(OH)2D3 has a potential to affect the inflammatory process by modulating the expression of neutrophil genes.

Inflection point of ascending aortic waveform is a powerful predictor of restenosis after percutaneous transluminal coronary angioplasty.

BACKGROUND: Although it was reported that the pulsatility of ascending aortic pressure is closely related to restenosis after percutaneous transluminal coronary angioplasty (PTCA), it is not known whether the reflection period of ascending aortic pressure can predict restenosis after PTCA. The purpose of this study was to evaluate whether reflection in the arterial system can be used to predict restenosis after PTCA. METHODS: We used the inflection point as the reflection period index and measured the coronary artery diameter, aortic pressure, and inflection time before PTCA. We defined the inflection time as the time interval from the initiation of systolic pressure waveform to the inflection point. We prospectively investigated the effect of inflection time in relation to the subsequent risk of restenosis after PTCA in patients with coronary artery disease. RESULTS: Crude cumulative incidence rates of restenosis were 74.1% for the lowest, 33.3% for the middle, and 26.1% for the highest tertile of inflection point levels. After adjustments for age, gender, smoking habits, hypertension, type 2 diabetes, hypercholesterolemia, old myocardial infarction, vessel location, post-minimal lumen diameter, heart rate, and ejection fraction, the odds ratio of restenosis was 6.99 (95% confidence interval, 1.54 to 31.7) for the lowest tertile of the inflection time level compared with the highest tertile level. CONCLUSIONS: Inflection time is a powerful predictor of restenosis after PTCA.

Role for complement receptors (CD21/CD35) in the regulation of recombination activating gene expression in murine peripheral B cells.

A population of peripheral B cells have been shown to express recombination activating gene products, RAG-1 and RAG-2, which are considered to be involved in revising the B cell antigen receptor (BCR) in the periphery. BCR engagement has been reported to turn off RAG expression in peripheral B cells, whereas the same treatment has an opposite effect on immature B cells in the bone marrow. In contrast to receptor editing that is involved in the removal of autoreactivity in immature B cells, it has been shown that secondary V(D)J rearrangement in peripheral B cells, termed receptor revision, contributes to affinity maturation of antibodies. Here, we show that RAG-2 expression in murine splenic B cells was abrogated by the coligation of BCR with complement receptors (CD21/CD35) much more efficiently than by the engagement of BCR alone. On the other hand, the same coligation augmented proliferation of anti-CD40-stimulated B cells. These findings suggest a crucial role for CD21/CD35 in directing the conservation or the revision of BCRs in peripheral B cells.

Reflection in the arterial system and the risk of coronary heart disease.

BACKGROUND: Although it was reported that the augmentation index and inflection time are closely related to reflection in the arterial system and large artery function, it is not known whether these indices of the ascending aortic pressure waveform increase the risk of coronary heart disease (CHD). The purpose of this study was to evaluate whether the aortic reflection of the ascending aortic pressure waveform is related to an increased risk of CHD. METHODS: We enrolled 190 men and women who had chest pain, normal contractions, no local asynergy, and no history of myocardial infarction. We measured the ascending aortic pressure using a fluid-filled system. The inflection time was defined as the time interval from initiation of a systolic pressure waveform to the inflection point. We investigated the association between the inflection time and augmentation index of the ascending aorta and the risk of CHD. RESULTS: Both the inflection time and augmentation index were associated with an increased risk of CHD. The crude prevalence rates of CHD were 66.0% for the shortest quartile and 10.6% for the longest quartile of the inflection time, and 17.0% for the lowest quartile and 40.4% for the highest quartile of the augmentation index. The multiple-adjusted odds ratio of CHD was 30.8 (95% confidence interval [CI] 7.43-128.05) for the shortest quartile of the inflection time compared with the longest quartile and was 3.82 (95% CI 1.26-11.59) for the highest quartile of the augmentation index compared with the lowest quartile. CONCLUSIONS: The augmentation index and inflection time were associated with an increased risk of CHD.