Lactose, a disaccharide and main carbohydrate in milk, requires hydrolysis in the intestinal tract to release its monosaccharides galactose and glucose for use as energy source by enterocytes. This hydrolysis is catalyzed by the enzyme lactase, a β-galactosidase located in the brush border membrane of small intestinal enterocytes. In most mammals, lactase activity declines after the weaning, a condition known as lactase non-persistence (LNP). Lactase persistence (LP) is an autosomal dominant trait enabling the continued production of the enzyme lactase throughout adult life. Non-persistence or persistence of lactase expression into adult life being a polymorphic trait has been attributed to various single nucleotide polymorphisms in the enhancer region surrounding lactase gene (LCT). However, latest research has pointed to 'genetic-epigenetic interactions' as key to regulation of lactase expression. LNP and LP DNA haplotypes have demonstrated markedly different epigenetic aging as genetic factors contribute to gradual accumulation of epigenetic changes with age to affect lactase expression. This review will attempt to present an overview of latest insights into molecular basis of LNP/LP including the crucial role of 'genetic-epigenetic interactions' in regulating lactase expression.
Natto is a well-known traditional Japanese food produced by fermenting soybeans with Bacillus subtilis var natto. Here we found that the water-soluble viscous fraction of natto inhibits sucrose- or glucose-induced hyperglycemia in silkworms. The water-soluble viscous fraction treated with DNase I, RNase A, and proteinase K, followed by phenol extraction also suppressed sucrose-induced hyperglycemia in silkworms. The enzyme-treated polysaccharide fraction of natto inhibits glucose uptake by Caco-2 cells, human intestinal epithelial cells. These findings suggest that the polysaccharide components of natto selected on the basis of their suppressive effects on sucrose-induced hyperglycemia in silkworms inhibit glucose uptake by human intestinal cells.
We compared the pharmaceutical properties, such as surface tension, drop volume, nozzle inner diameter, and force to push the drug product out of the container (squeeze force), of purified sodium hyaluronate eye drops preparations of one brand-name (Hyalein) and 11 generic drugs used for treatment of keratoconjunctiva epithelial disorders, and examined product selection based on the needs of the patient. The surface tension of Nissin (51.0 dyn/cm) and Nitten (52.3 dyn/cm) was significantly lower than that of Hyalein (62.8 dyn/cm), whereas Nitten PF (69.5 dyn/cm) was significantly higher than Hyalein. The drop volume of Tearbalance (42.4 mg), Nissin (43.7 mg), and Nitten (42.7 mg) was significantly lower than that of Hyalein (50.4 mg). We compared the squeeze force using a wearable touch sensor (Haptic Skill Logger: HapLog®) and digital force gauge (DF). The squeeze force of HapLog® showed values of about 1.7- to 3.5-fold higher than that of DF. Moreover, the squeeze force of Eyecare (34.0 N), Kyorin (35.4 N), and Nitten PF (44.3 N) by HapLog® was significantly higher than that of Hyalein (10.5 N). In contrast, the squeeze force of Kyorin (20.8 N) and Nitten PF (25.0 N) by DF was significantly higher than that of Hyalein (12.2 N). Two questionnaire surveys on the feeling of instillation of eye drops revealed a strong negative correlation between feeling of use and squeeze force.
The pulse wave transit time (PWTT) is easily measured as the time from the R wave of an electrocardiogram to the arrival of the pulse wave measured by an oxygen saturation monitor at the earlobe. We investigated whether the change of PWTT during exercise testing reflects cardiopulmonary function. Eighty-nine cardiac patients who underwent cardiopulmonary exercise testing (CPX) were enrolled. We analyzed the change of PWTT during exercise and the relationship between the shortening of the PWTT and CPX parameters. PWTT was significantly shortened from rest to peak exercise (204.6 ± 33.6 vs. 145.6 ± 26.4 msec, p < 0.001) in all of the subjects. The patients with heart failure had significantly higher PWTT at peak exercise than the patients without heart failure (152.7 ± 27.1 vs. 140.4 ± 24.8 msec, p = 0.031). The shortening of PWTT from rest to peak exercise showed significant positive correlations with the peak O2 uptake (VO2) (r = 0.56, p < 0.001), anaerobic threshold (r = 0.40, p = 0.016), and % increase of systolic blood pressure during exercise (r = 0.75, p < 0.001), and a negative correlation with the slope of the increase in ventilation versus the increase in CO2 output (VE-VCO2 slope) (r = – 0.42, p = 0.010) in the patients with heart failure. PWTT was shortened during exercise as the exercise intensity increased. In the patients with heart failure, the shortening of PWTT from rest to peak exercise was smaller in those with lower exercise capacity and those with higher VE-VCO2 slope, an established index known to reflect the severity of heart failure.
Up to 50% peripheral intravenous catheters (PIVs) are removed prematurely because of failures. Catheter failure (CF) leads to replacement and is a great concern for patients and medical staff. It is known that visualization of catheters and vessels with ultrasonography (US) during placement prevents CF. However, US is not a common technique for general nurses. In order to standardize US-assisted PIV placement techniques, an algorithm is needed. This study aimed to develop an algorithm using US-assisted PIV placement to reduce CF rate. Furthermore, to evaluate the effectiveness of the algorithm, CF rates were compared before and after intervention. A pretest-posttest study was performed. The intervention was PIV placement by 23 nurses undergoing training sessions for the algorithm. Intention to treat, per protocol analyses were applied. Logistic regression analysis was used for factor analysis. The CF rate in the pre-intervention group 35.2% (19/54) did not significantly differ from post-intervention group 33.6% (48/143) (p = 0.831), yet significantly differ from complete algorithm-use group 8.7% (2/23; p = 0.017). In factor analysis, compliance to the algorithm was significantly correlated with CF (p = 0.032). The compliance rate was low 16.1% (23/143). Algorithm compliance reduced CF by confirming appropriate catheter tip position from the insertion to the securement phase. This algorithm effectively reduced CF, however, the compliance rate was unacceptable. In order to increase the compliance rate, modified algorithm and new visualizing technology is required.
Lysosomes are involved in many cellular functions, and in turn lysosomal dysfunction underlies a variety of diseases, including cancer and neurodegenerative diseases. Lysosomes are distributed broadly in the cytoplasm and can move throughout the cell in kinesin- and dynein-dependent manners. Although many mechanisms of lysosomal transport have been reported, how lysosomal transport is regulated has yet to be fully elucidated. In this study we analyzed c-Jun NH2-terminal kinase-associated leucine zipper protein (JLP), an adaptor of kinesin and dynein motor proteins, and found that lysosomes were localized toward the cell periphery in JLP knockdown cells, leading to the impairment of autophagosome-lysosome fusion. Furthermore, we performed rescue experiments using wild-type JLP and its various deletion mutants. The results indicated that JLP may regulate lysosome localization and autophagy through interaction of JLP with kinesin-1 heavy chain, but not with dynactin p150Glued or lysosomal transmembrane protein 55b. Our findings provide new insights into the mechanisms of lysosomal trafficking regulation. This study contributes to the understanding of how lysosomes exert their multiple functions, potentially leading to the identification of molecular targets for diseases caused by lysosomal dysfunction.
Acute urinary tract infection (UTI) is a highly common clinical condition. Although bacterial culture is the gold standard diagnostic test, false negative results may be possible, leading to the pathogen being unidentified. In recent years, bacterial DNA sequencing analysis has garnered much attention, but clinical studies are rare in Japan. In this study, we assessed the usefulness of next-generation DNA sequencing (NGS) analysis for acute UTI patients. We thus performed an observational, retrospective case series study. Urine and blood samples were collected from ten acute UTI patients, of whom four had also been diagnosed with urosepsis. Seven variable regions of bacterial 16S rRNA genes were amplified by PCR and then sequenced by IonPGM. The identified bacterial species were compared with those identified using the culture tests and the clinical parameters were analyzed. As a result, the NGS method effectively identified predominant culture-positive bacteria in urine samples. The urine NGS also detected several culture-negative species, which have been reported to be potentially pathogenic. Out of four urosepsis cases, three were pathogen-positive in blood NGS results, while two were pathogen-negative in blood culture. In one sepsis case, although blood culture was negative for Escherichia coli, this species was detected by blood NGS. For non-sepsis cases, however, blood NGS, as well as blood culture, was less effective in detecting bacterial signals. In conclusion, NGS is potentially useful for identifying pathogenic bacteria in urine from acute UTI patients but is less applicable in patients who do not meet clinical criteria for sepsis.
Our earlier study investigated the incidence of severe abnormal behavior associated with neuraminidase inhibitors (NIs), but some studies have specifically examined the association of oseltamivir use and moderately abnormal behavior. Therefore, this study was undertaken to assess associations between moderately abnormal behavior and administered drugs. All cases of patients with influenza who exhibited moderately abnormal behavior were reported to us by physicians of all sentinel clinics and hospitals for influenza throughout Japan. Open Data of the National Database of Electronic Medical Claims include the numbers of patients diagnosed as having influenza who were prescribed NI. Incidence by NI was tested using Fisher's exact test. We received 518 moderately abnormal cases in 5-9-year-olds and 207 moderately abnormal behavior cases in 10-19-year-olds. The incidence among NI ranged from 193 per one million influenza patients in laninamivir among 10-19-year-olds to 1021 for peramivir among 5-9-year-olds. Estimation results revealed the order of risk among NIs as peramivir, oseltamivir, zanamivir and laninamivir in moderate abnormal behavior. Because of data limitations, risk among patients with and without NI cannot be compared.
Metabolic syndrome is a cluster of risk factors for cardiovascular disease and type 2 diabetes mellitus. The risk factors include hypertension, dyslipidemia, hyperglycemia, and central obesity. Various diagnostic criteria have been proposed by different organizations over the past decade. The utilization of traditional Chinese medicine to treat metabolic syndrome has received increasing attention due to its wide availability. In this paper, we report the case of a 68-year-old patient with hypertension, hypercholesterolemia, borderline diabetes, and obesity, who showed an improvement in metabolic syndrome on the administration of 7.5 g of Kangen-karyu extract per day. After 6 months, the levels of serum total cholesterol, low-density lipoprotein-cholesterol, triglycerides, hemoglobin A1c were decreased. The abdominal circumference and body weight were decreased following administration. At that time, the somatic and subjective symptoms had partially disappeared. Herein, we present and discuss the evidence supporting the use of Kangen-karyu extract against metabolic syndrome.
The SARS-CoV-2 virus emerged in December 2019 and then spread rapidly worldwide, particularly to China, Japan, and South Korea. Scientists are endeavoring to find antivirals specific to the virus. Several drugs such as chloroquine, arbidol, remdesivir, and favipiravir are currently undergoing clinical studies to test their efficacy and safety in the treatment of coronavirus disease 2019 (COVID-19) in China; some promising results have been achieved thus far. This article summarizes agents with potential efficacy against SARS-CoV-2.