Salt taste perception and blood pressure levels in population-based samples: the Circulatory Risk in Communities Study (CIRCS).

To examine the associations of salt perception with salt intake and blood pressure levels in general populations, we performed a cross-sectional study in two communities where salt intake level is different, Akita and Osaka in Japan. Taste perception (detection for certain taste and recognition for salt taste) was determined using a Na-impregnated test strip for 1024 Akita and 1199 Osaka adults aged 30-74 years. The proportions of detection for 0·1 % salt were 61, 62, 79, and 79 % in Akita men, Osaka men, Akita women and Osaka women, respectively. The corresponding proportions of not recognising of 1·6 % salt taste (>1·6 %) were 34, 30, 16 and 21 %. Detection threshold was higher in Akita than in Osaka for women aged 60-74 years, and recognition threshold was lower in Akita than in Osaka for women aged 30-59 and 60-74 years. The high detection (≥0·4 %) and recognition (>1·6 %) thresholds of salt taste were associated with higher salt intake scores for Akita men aged 30-59 years, whose detection and recognition thresholds tended be positively associated with systolic and diastolic blood pressures (SBP and DBP) after adjustment for potential confounders. Among Akita elderly men, detection threshold tended to be positively associated with SBP and DBP, while among Akita middle-aged women, recognition threshold was associated with SBP. In conclusion, the high thresholds of salt perception were inversely associated with salt intake for Akita middle-aged men and with blood pressure levels for Akita middle-aged and elderly men and middle-aged women.

Effect of high-intensity interval walking on microvascular endothelial function among community-dwelling older people.

AIM: To investigate the effects of high-intensity interval exercise training on microvascular endothelial function among community-dwelling older people. METHODS: We analyzed the data from a nonrandomized controlled trial. This study's participants were 48 men (aged 75 ± 5 years; exercise training group, n = 24; control group, n = 24) and 83 women (aged 75 ± 4 years; exercise training group, n = 36; control group, n = 47). The exercise training group underwent a high-intensity interval walking training for 5 months. RESULTS: In the exercise group, 100% and 91.7% of men and women, respectively, achieved brisk walking times ≥50 min/week. The change in the reactive hyperemia index significantly differed between the groups of men, whereas that in the control group was not significant; however, a significant increase was observed in the exercise training group. Among women, changes in the reactive hyperemia index were not significant in either group; however, for women in the exercise training group, these changes negatively and positively correlated with the change in body mass index (Spearman's rho = -0.342; P = 0.041) and baseline body mass index (rho = 0.362, P = 0.030), respectively. Additionally, the distribution of body mass index was broader in women than in men. CONCLUSIONS: Interval walking training increased the reactive hyperemia index in men rather than in women. A higher variation in baseline body mass index may be associated with no statistical increase in reactive hyperemia index in women. Geriatr Gerontol Int 2023; 23: 103-110.

Effects of interval-walking training on blood pressure in community-dwelling Japanese older adults.

BACKGROUND: The hypotensive effects of high-intensity interval training have been reported; however, studies on older adults are few. This study aimed to examine whether interval-walking training (IWT), a home-based program of high-intensity interval training, reduces blood pressure (BP) levels when compared with a non-intervention group in community-dwelling older adults. METHODS: An intervention study was conducted with 55 men (age, 75±5 years; IWT/control groups, N.=27/28) and 100 women (75±5 years; N.=47/53). The IWT regimen was as follows: fast (high-intensity) walking at 70-85% of the peak aerobic capacity and normal (light-intensity) walking at approximately 40% of the peak aerobic capacity for 3 min each, ≥5 times/walking day, and ≥4 days/week for 5 months. Systolic, diastolic, and mean arterial BPs (SBP, DBP, and MAP, respectively) were measured in the supine posture. RESULTS: The mean baseline SBP/DBP was 132/78 mmHg in men and 131/72 mmHg in women. Five-month changes in SBP, DBP, or MAP did not significantly differ between the IWT and control groups in either sex. The weekly fast-walking time in the IWT group was negatively correlated with changes in DBP (Spearman's ρ=-0.383, P=0.049) and MAP (ρ=-0.444, P=0.021) only in men. CONCLUSIONS: Though present findings did not indicate significant hypotensive effects of IWT in community-dwelling older adults, men with longer fast-walking times experienced greater BP decreases. Further studies with sufficient sample sizes are needed to determine the factors modulating the effects of the proposed training program.

Salivary Microbiota Associated with Peripheral Microvascular Endothelial Dysfunction.

AIMS: Oral health is associated with atherosclerotic cardiovascular disease (ACVD). We previously identified the salivary microbiota characteristics of patients with ACVD. However, whether salivary microbiota is characteristic under impaired vascular endothelial function before ACVD onset remains unclear. Therefore, we aimed to evaluate the characteristics of salivary microbiota associated with peripheral microvascular endothelial dysfunction. METHODS: We collected saliva samples from 172 community-dwelling elderly individuals without a history of ACVD and performed 16S rRNA metagenomic analysis. We assessed the peripheral microvascular endothelial function using reactive hyperemia index (RHI) and compared the salivary microbiota in the groups with normal (RHI ≥ 2.10), borderline, and abnormal (RHI ＜1.67) peripheral endothelial function. Furthermore, we applied machine learning techniques to evaluate whether salivary microbiota could discriminate between individuals with normal and abnormal endothelial function. RESULTS: The number of operational taxonomic units (OTUs) was higher in the abnormal group than in the normal group (p=0.037), and differences were found in the overall salivary microbiota structure (unweighted UniFrac distances, p=0.038). The linear discriminant analysis (LDA) effect size (LEfSe) algorithm revealed several significantly differentially abundant bacterial genera between the two groups. An Extra Trees classifier model was built to discriminate between groups with normal and abnormal vascular endothelial function based on the microbial composition at the genus level (AUC=0.810). CONCLUSIONS: The salivary microbiota in individuals with endothelial dysfunction was distinct from that in individuals with normal endothelial function, indicating that the salivary microbiota may be related to endothelial function.

Effect of polyethyleneglycol spacer on the binding properties of nuclear localization signal-modified liposomes to isolated nucleus.

The nuclear delivery process is a crucial barrier to successful gene delivery, especially in non-dividing cells. We previously proposed a novel strategy for the nuclear delivery of plasmid DNA (pDNA), in which the pDNA is encapsulated in lipid bilayers that had been modified with nucleus-targeting signals, including nuclear localizing signals derived from SV40 (NLS) or sugar units. In the present study, we report on an investigation of the effect of the topology of the liposome-modified NLS on its ability to bind to the isolated nucleus. NLS was directly attached to a liposome (NLS-Lip) by incorporating stearylated NLS (STR-NSL), or by modification with a polyethyleneglycol (PEG) spacer (NLS-PEG-Lip). NLS-unmodified liposomes (PEG-Lip) were used as a control. The liposomes, after labeling with 7-nitrobenz-2-oxa-1,3-diazole (NBD), were incubated with a cell homogenate derived from JAWS II cells, followed by isolation of the nuclear fraction by centrifugation. The PEG-Lip preparation showed negligible binding to the nucleus. In contrast, the binding of NLS-Lips to the nucleus gradually increased in a STR-NLS density-dependent manner. Interestingly, the binding of NLS-PEG-Lips to the nucleus is highly effective even at low density, suggesting that the presence of the PEG spacer is an important factor in improving the binding activity of NLS-modified liposomes to the nucleus. This information will be useful for the design of nucleus-targeting carriers.

Multi-layered nanoparticles for penetrating the endosome and nuclear membrane via a step-wise membrane fusion process.

Efficient targeting of DNA to the nucleus is a prerequisite for effective gene therapy. The gene-delivery vehicle must penetrate through the plasma membrane, and the DNA-impermeable double-membraned nuclear envelope, and deposit its DNA cargo in a form ready for transcription. Here we introduce a concept for overcoming intracellular membrane barriers that involves step-wise membrane fusion. To achieve this, a nanotechnology was developed that creates a multi-layered nanoparticle, which we refer to as a Tetra-lamellar Multi-functional Envelope-type Nano Device (T-MEND). The critical structural elements of the T-MEND are a DNA-polycation condensed core coated with two nuclear membrane-fusogenic inner envelopes and two endosome-fusogenic outer envelopes, which are shed in stepwise fashion. A double-lamellar membrane structure is required for nuclear delivery via the stepwise fusion of double layered nuclear membrane structure. Intracellular membrane fusions to endosomes and nuclear membranes were verified by spectral imaging of fluorescence resonance energy transfer (FRET) between donor and acceptor fluorophores that had been dually labeled on the liposome surface. Coating the core with the minimum number of nucleus-fusogenic lipid envelopes (i.e., 2) is essential to facilitate transcription. As a result, the T-MEND achieves dramatic levels of transgene expression in non-dividing cells.