Home Meal Replacement Fortified with Eggshell Powder and Vitamin D Prevents Bone Loss in Postmenopausal Women: A Randomized, Double-Blind, Controlled Study.

Calcium and vitamin D deficiencies have been ongoing problems in Koreans due to a lack of food sources of calcium and vitamin D. Postmenopausal women aged 50 to 64 years (n = 25) were randomly assigned to consume three home meal replacements (HMRs)/week with (treatment) and without (control) eggshell powder and vitamin D for 6 months. Additionally, subjects who agreed to continue the study consumed the same three HMRs/week for an additional 6 months in this randomized double-blind study. We confirmed the high compliance of the study participants by analyzing carotenoids, the bioactive substances of HMRs, in the blood. The treatment group consumed an additional 261 mg/d of calcium and 10.3 µg/d of vitamin D from the HMRs, thus meeting the recommended intakes of calcium and vitamin D for Koreans. As a result of consuming fortified HMRs for 6 months, the decline in femoral neck bone density was significantly reduced in the treatment group (p = 0.035). This study indicates that inexpensive eggshell powder may be a good source of calcium for populations with low consumption of milk and dairy products. Additionally, functional HMRs fortified with eggshell powder and vitamin D can be a good dietary strategy for bone health.

Short-term Changes in Thyroid-Stimulating Hormone Level after Body Fat Reduction via Partial Meal Replacement.

BACKGROUND: Serum thyroid-stimulating hormone (TSH) levels change during body weight reduction. However, the changes that occur during short-term body weight control interventions remain controversial. Thus, this study aimed to evaluate the changes in TSH levels according to body fat reduction. METHODS: We performed a 3-month intervention study involving partial meal replacement. Forty-nine participants completed the study. Correlations between changes in TSH levels and other body composition parameters were determined. The subjects were divided into two groups according to their body fat reduction (>1 kg, n=20; <1 kg, n=29). The changes in metabolic parameters, including TSH levels, were compared. For significant values, a multivariate analysis was performed after adjustment to evaluate the relationship between TSH changes and body fat reduction. RESULTS: The 3-month intervention caused favorable changes in body proportions and metabolic parameters. TSH levels changed significantly only after changes in total body fat, showing a partial correlation. Changes in TSH levels were significantly different between groups (P=0.014). Moreover, the change in TSH levels was significantly different after adjustment (P=0.012). CONCLUSION: A body fat reduction, especially >1 kg, can reduce serum TSH concentrations in subjects with metabolic syndrome after short-term body weight intervention.

Enhancement of Gene Editing and Base Editing with Therapeutic Ribonucleoproteins through In Vivo Delivery Based on Absorptive Silica Nanoconstruct.

Key to the widespread and secure application of genome editing tools is the safe and effective delivery of multiple components of ribonucleoproteins (RNPs) into single cells, which remains a biological barrier to their clinical application. To overcome this issue, a robust RNP delivery platform based on a biocompatible sponge-like silica nanoconstruct (SN) for storing and directly delivering therapeutic RNPs, including Cas9 nuclease RNP (Cas9-RNP) and base editor RNP (BE-RNP) is designed. Compared with commercialized material such as lipid-based methods, up to 50-fold gene deletion and 10-fold base substitution efficiency is obtained with a low off-target efficiency by targeting various cells and genes. In particular, gene correction is successfully induced by SN-based delivery through intravenous injection in an in vivo solid-tumor model and through subretinal injection in mouse eye. Moreover, because of its low toxicity and high biodegradability, SN has negligible effect on cellular function of organs. As the engineered SN can overcome practical challenges associated with therapeutic RNP application, it is strongly expected this platform to be a modular RNPs delivery system, facilitating in vivo gene deletion and editing.

Effects of narrowband ultraviolet B exposure on serum 25-hydroxyvitamin D concentrations: A pilot study.

It is known that ultraviolet B exposure increases serum 25-hydroxyvitamin D(25(OH)D) concentrations. However, little is known about the influence of narrowband ultraviolet B exposure from a light-emitting diode (NBUVB-LED) on serum 25(OH)D levels. Thus, the purpose of this study was to investigate the effect of NBUVB-LED exposure on serum 25(OH)D concentrations. Two healthy adults were enrolled in this pilot study. Their skin was exposed to ultraviolet B light (60 mJ/cm2) 3 times a week for 4 weeks in the first intervention and every day for 4 weeks in the second intervention. Serum levels of 25(OH)D were measured every 2 weeks. Serum 25(OH)D levels were decreased in both subjects at the end of the first intervention (32.1 → 21.4 ng/mL, 33.9 → 21.4 ng/mL, respectively), whereas serum 25(OH)D levels were increased in the 2 weeks of the second intervention (29.5 and 28.0 ng/mL, respectively). At the end of the second intervention, the 25(OH)D concentrations were 19.0 and 20.4 ng/mL, respectively. NBUVB-LED exposure might increase serum 25(OH)D concentrations. Future studies should expand the number of participants and adjust for confounding factors.

Adenine base editor engineering reduces editing of bystander cytosines.

Adenine base editors (ABEs) catalyze specific A-to-G conversions at genomic sites of interest. However, ABEs also induce cytosine deamination at the target site. To reduce the cytosine editing activity, we engineered a commonly used adenosine deaminase, TadA7.10, and found that ABE7.10 with a D108Q mutation in TadA7.10 exhibited tenfold reduced cytosine deamination activity. The D108Q mutation also reduces cytosine deamination activity in two recently developed high-activity versions of ABE, ABE8e and ABE8s, and is compatible with V106W, a mutation that reduces off-target RNA editing. ABE7.10 containing a P48R mutation displayed increased cytosine deamination activity and a substantially reduced adenine editing rate, yielding a TC-specific base editing tool for TC-to-TT or TC-to-TG conversions that broadens the utility of base editors.

Effect of eradicating hydrogen-forming small intestinal bacterial overgrowth with rifaximin on body weight change.

Hydrogen formed by small intestinal bacterial overgrowth in patients with non-constipated irritable bowel syndrome has an inverse relationship with obesity. However, the effect of eradicating small intestinal hydrogen-producing bacterial overgrowth on the body weight of these patients has not yet been reported. The aim of this study was to investigate body weight changes after eradicating small intestinal bacterial overgrowth with rifaximin treatment in patients with non-constipated irritable bowel syndrome.We reviewed the charts of patients with non-constipated irritable bowel syndrome who showed abdominal symptoms with documented lactulose hydrogen breath test results in order to diagnose small intestinal bacterial overgrowth. A total of 153 patients were enrolled in the study and divided into quartiles according to body mass index (BMI) and body weight.In the lowest body weight quartile, the BMI and body weight were significantly increased (0.4 kg/m, P = .038; 0.6 kg, P = .010, respectively) in patients with negative lactulose hydrogen breath tests after rifaximin treatment. However, there was no significant change in body weight in the other quartiles. Despite treatment with rifaximin for 12 weeks, there was no change in BMI or body weight in any group of patients with consistently positive lactulose hydrogen breath tests.Eradication of hydrogen formed by small intestinal bacterial overgrowth does not cause clinically significant changes in body weight.

Changes in Fecal Calprotectin After Rifaximin Treatment in Patients With Nonconstipated Irritable Bowel Syndrome.

BACKGROUND: Fecal calprotectin, an indicator of colonic inflammation, is associated with nonconstipated irritable bowel syndrome. Rifaximin is an antibiotic used to treat nonconstipated irritable bowel syndrome. We performed a retrospective review of patient charts to investigate the changes in fecal calprotectin levels and intestinal symptoms following treatment with rifaximin in patients with nonconstipated irritable bowel syndrome with elevated fecal calprotectin. METHODS: This study included 198 patients presenting with gastrointestinal complaints consistent with Rome III criteria for irritable bowel syndrome. We treated them with rifaximin for 4-12 weeks, until fecal calprotectin levels were normalized, and divided these into 4-, 8-, and 12-week groups according to the treatment period. Fecal calprotectin levels and gastrointestinal symptoms were assessed following rifaximin therapy. RESULTS: A total of 162 subjects achieved normalized fecal calprotectin values. Of these, most patients who used rifaximin for 8 or 12 weeks showed a significant improvement in gastrointestinal symptoms by the fourth week of treatment, and gradually improved symptoms after 4 weeks. Fecal calprotectin levels were reduced with concomitant improvement of clinical symptoms. In addition, 36 patients who had elevated fecal calprotectin even after 12 weeks of rifaximin treatment showed a gradual reduction in gastrointestinal symptoms and fecal calprotectin during the course of treatment for 12 weeks. CONCLUSIONS: These findings suggest that fecal calprotectin might be a useful biomarker for measuring the effect of rifaximin therapy in nonconstipated irritable bowel syndrome patients with elevated fecal calprotectin values.

A Randomized Clinical Trial of Synbiotics in Irritable Bowel Syndrome: Dose-Dependent Effects on Gastrointestinal Symptoms and Fatigue.

BACKGROUND: This double-blind, randomized controlled design study aimed to assess the dose-dependent effects of synbiotics on gastrointestinal symptoms of and fatigue in irritable bowel syndrome (IBS). METHODS: Thirty subjects with IBS were randomly assigned into the following three groups and received 2 capsules a day for 8 weeks: (1) high-dose (2 capsules of synbiotics); (2) low-dose (1 capsule of synbiotics and 1 capsule of placebo); and (3) placebo (2 capsules of placebo). At baseline and 8 weeks, they completed the study questionnaires. RESULTS: Two subjects in the high-dose group were lost to follow-up, leaving a total of 28 patients for the analysis. After 8 weeks, abdominal discomfort, abdominal bloating, frequency of formed stool, fatigue Visual Analog Scale (VAS), and Multidimensional Fatigue Inventory were significantly different among the groups (P=0.002, 0.006, 0.007, 0.028, and 0.041, respectively, by Kruskal-Wallis test). However, only abdominal discomfort, abdominal bloating, frequency of formed stool, and fatigue VAS were significantly improved in the high-dose group compared with those in the placebo group (P=0.002, 0.003, 0.002, and 0.013, respectively) by Mann-Whitney test with Bonferroni correction. No adverse drug reactions were reported. CONCLUSION: High-dose synbiotics were superior to placebo in improving bowel symptoms and fatigue of IBS patients, suggesting that synbiotic dosage plays an important role in the treatment of IBS.

The Therapeutic Effect of a Multistrain Probiotic on Diarrhea-Predominant Irritable Bowel Syndrome: A Pilot Study.

BACKGROUNDS: Recent studies suggest that diarrhea-predominant irritable bowel syndrome (IBS) is associated with intestinal bacterial microflora, colonic inflammation, and small intestinal bacterial overgrowth (SIBO). The purpose of this study was to evaluate the effect of a multistrain probiotic intake on these associated factors in patients with diarrhea-predominant IBS. METHODS: The recruited volunteers were adults who were diagnosed with diarrhea-predominant IBS according to the Rome III criteria. After 8 weeks of probiotic ingestion, changes in gastrointestinal symptoms, fecal microbiome, SIBO, and fecal calprotectin were determined. RESULTS: There was an increase in beneficial bacteria (41.2 ± 16.8% vs. 53.7 ± 15.3%, P = 0.018) and a decrease in harmful bacteria (13.0 ± 13.9% vs. 4.7 ± 4.0%, P = 0.010) in the microbial stool analysis. The SIBO prevalence also decreased at the end of treatment. However, the average levels of fecal calprotectin showed a decreasing tendency, without reaching statistical significance (364.4 ± 729.1 mg/kg vs. 200.9 ± 347.6 mg/kg, P = 0.375). CONCLUSION: Treatment with a multistrain probiotic for 8 weeks led to significant increases in beneficial bacteria in the gut as well as the improvement of gastrointestinal symptoms. This study is registered at the Clinical Research Information Service (KCT0002906).

Combined effect of serum gamma-glutamyltransferase and uric acid on incidence of diabetes mellitus: A longitudinal study.

Gamma-glutamyltransferase (GGT) and uric acid (UA) are novel diabetes risk factors. However, little is known about the combined effects of GGT and UA on the development of diabetes. Here, we assessed the combined effects of GGT and UA on the development of diabetes in a Korean population.We evaluated 1983 women and 2687 men without diabetes. From the baseline health screening to the follow-up examination, the development of diabetes, based on changes in GGT and UA quartile levels, was analyzed. Furthermore, the quartile of GGT and quartile of UA were analyzed together to determine any synergistic effect from the 4th quartile of GGT and UA on the development of diabetes.In women, the development of diabetes gradually increased with an increase in the circulating levels of GGT and UA. For the highest quartile of GGT and UA, hazard ratios of diabetes compared with the lowest quartile were 3.88 (95% confidence interval [CI]: 1.12-13.43, P = .032) and 7.58 (95% CI: 2.17-26.42, P = .002) after adjusting for confounders, respectively. Hazard ratios of diabetes after combining both 4th quartiles of GGT and UA were 5.29 (95% CI: 1.87-15.18, P = .002), as compared with the first and second quartiles. In men, however, the development of diabetes was not significantly different among the quartiles of UA.GGT and UA levels can synergize in predicting the development of diabetes in Korean women.

Enzymatic susceptibility of wheat gluten after subcritical water treatment.

Subcritical water (SCW) hydrolysis is an alternative to traditional methods of protein hydrolysis that uses water as a reaction medium. In this study, the effect of SCW treatment on heat-induced conformational changes in wheat gluten and its relation to enzymatic susceptibility were investigated. The degree of deamidation increased rapidly from 12.5 to 47.4% with increase in the temperature range of 160-220 °C. Protein solubility increased in a similar pattern with degree of deamidation and almost all protein was solubilized after treatment with SCW at 200 °C. SCW treatment in a particular time-temperature combination results in a significant decrease in enzymatic susceptibility. After SCW treatment at 220 °C for 20 min, enzymatic susceptibility of gluten protein was exceedingly decreased to nearly complete loss. Because of excess degradation and deamidation and small molecular size (less than 6500 Da) many hydrolysis sites disappear and are difficult to access by protease.

The Cut-off Value of Blood Mercury Concentration in Relation to Insulin Resistance.

BACKGROUND: Increased blood mercury concentration is associated with inflammation, and chronic inflammation can cause insulin resistance. We examined the cut-off value of blood mercury in relation to an increased score on the homeostasis model assessment for insulin resistance (HOMA-IR). METHODS: We used data from the Korean National Health and Nutrition Examination Survey (2008-2010). Relevant data from 5,184 subjects (2,523 men and 2,661 women) were analyzed cross-sectionally. General linear analysis was performed to evaluate the relationship between HOMA-IR score and blood mercury concentration. In addition, we determined the cut-off value of blood mercury concentration in relation to increased HOMA-IR score (> 2.34) using an ROC curve. RESULTS: The mean value of blood mercury concentration in men and women was 5.88 µg/L and 4.11 µg/L, respectively. In men, comparing to the first quartile, HOMA-IR score increased significantly in the third and fourth blood mercury quartiles. In women, however, the increase in HOMA-IR score was not significant. The cut-off value that best represented the association between increased HOMA-IR score and blood mercury concentration in men was found to be 4.71 µg/L. CONCLUSION: Blood mercury concentration was associated with increased HOMA-IR score in men, and the cut-off value of blood mercury concentration that was correlated with increased HOMA-IR score was around 4.71 µg/L.

Dietary Calcium Intake May Contribute to the HOMA-IR Score in Korean Females with Vitamin D Deficiency (2008-2012 Korea National Health and Nutrition Examination Survey).

BACKGROUND: Vitamin D and calcium are important factors involved in the regulation of blood glucose and insulin secretion. The Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) score is a useful variable for evaluating insulin resistance, and therefore we cross-sectionally compared HOMA-IR scores according to serum vitamin D levels and dietary calcium intake. METHODS: We selected data from healthy males (n=5,163) and females (n=7,506) analyzed over 5 years (2008-2012) via the Korea National Health and Nutrition Examination Survey (KNHANES). We calculated HOMA-IR scores and compared them according to serum 25-hydroxyvitamin D (25(OH)D) concentration classification (<20, 20-30, >30 ng/mL) and dietary calcium quintile after adjustment for relevant variables using complex sample analysis. Comparisons were done after data weighting. RESULTS: The mean dietary calcium intake in males and females was 558.1 mg/day and 445.9 mg/day, respectively. The mean serum 25(OH)D concentration in males and females was 19.4 ng/mL and 16.8 ng/mL, respectively. After adjustment for relevant variables, HOMA-IR score was significantly correlated with serum 25(OH)D concentration and dietary calcium intake in females, whereas it was only correlated with serum 25(OH)D concentration in males. HOMA-IR was significantly lower in the top quintile of dietary calcium intake (mean, 866 mg/day) within females with vitamin D deficiency (P=0.047). CONCLUSION: Adequate dietary calcium intake may be important for normal HOMA-IR in females with vitamin D deficiency.

Sol-gel phase transitions in a photochromic spiropyran-modified material by incorporation in a hydrogel.

Photochromic spiropyran-modified material 1 and hydrogelator 2 bearing sugar and D-alanine moieties were prepared and their thermal- and photo-responsive properties in aqueous solution were investigated by NMR, CD, PXRD, DSC, and UV-vis spectroscopy. The xerogels [1 + 2] (1:1-20 wt%) with various ratios obtained from water showed well-developed fibril structures with diameters of 50-100 nm and length of several hundred micrometers. Interestingly, after irradiation with UV light, these aggregates were destroyed because the closed form (SP) of spiropyran unit of 1 changes to the corresponding merocyanine form (MC). In contrast, further heating led to the original hydrogels [1 + 2], due to the transformation of the opened form (MC) of 1 into the corresponding spiropyran form (SP). Thus, the spiropyran unit of 1 played an important role in the gelation of water by interacting with the gelators in a host-guest interaction that could modify the superstructures and sensitively affect their stability.

Creation of double silica nanotubes by using crown-appended cholesterol nanotubes.

New crown-appended cholesterol-based organogelators 1-3, which have one or two cholesterol skeletons as a chiral aggregate-forming site, two amino groups as an acidic proton binding site, and one crown moiety as a cation binding site, were synthesized, and the gelation ability was evaluated in organic solvents. These gelators could gelatinize several organic solvents under 1.0 wt %, indicating that 1-3 act as a versatile gelator of various organic solvents. We observed CD spectra of the acetic acid or propionic acid gels of 1-3 to characterize the aggregation mode in the organogel system. In the CD spectrum of the acetic acid gel 1, the positive sign for the first Cotton effect indicates that the dipole moments of azobenzene chromophores tend to orient into the clockwise direction. On the other hand, propionic acid gels 2 and 3, bearing only one cholesterol, moiety exhibit a negative sign for the first Cotton effect, strongly suggesting that the dipole moments of the azobenzene chromophores orient into the anticlockwise direction. The TEM images of the 1+acetic acid gel resulted in the helical ribbon and tubular structures. Sol-gel polycondensation of tetraethoxysilane (TEOS) was carried out with 1-3 as templates in the gel phase. The silica obtained from the 1+acetic acid gel showed the helical ribbon with 200-1700 nm width and the tubular structure of the silica with constant about 560 nm outer diameter. As far as can be recognized, all the helicity possesses a right-handed helical motif. Since the exciton coupling band of the organogel also shows P (right-handed) helicity, we consider that a microscopic helicity is reflected by a macroscopic helicity. On the other hand, the tubular structure of the silica obtained from the organogels 2 and 3 is somewhat different from that prepared from the organogel 1. The careful examination of SEM and TEM pictures revealed that the tube wall of the silica features a roll-paper-like multilayer structure. Thus, this paper demonstrates successful and rare examples for precise transcription of gel superstructures into inorganic silica materials.