Safety and Feasibility of Long-term Intravenous Sodium Nitrite Infusion in Healthy Volunteers

BACKGROUND: Infusion of sodium nitrite could provide sustained therapeutic concentrations of nitric oxide (NO) for the treatment of a variety of vascular disorders. The study was developed to determine the safety and feasibility of prolonged sodium nitrite infusion. METHODOLOGY: Healthy volunteers, aged 21 to 60 years old, were candidates for the study performed at the National Institutes of Health (NIH; protocol 05-N-0075) between July 2007 and August 2008. All subjects provided written consent to participate. Twelve subjects (5 males, 7 females; mean age, 38.8±9.2 years (range, 21-56 years)) were intravenously infused with increasing doses of sodium nitrite for 48 hours (starting dose at 4.2 µg/kg/hr; maximal dose of 533.8 µg/kg/hr). Clinical, physiologic and laboratory data before, during and after infusion were analyzed. FINDINGS: The maximal tolerated dose for intravenous infusion of sodium nitrite was 267 µg/kg/hr. Dose limiting toxicity occurred at 446 µg/kg/hr. Toxicity included a transient asymptomatic decrease of mean arterial blood pressure (more than 15 mmHg) and/or an asymptomatic increase of methemoglobin level above 5%. Nitrite, nitrate, S-nitrosothiols concentrations in plasma and whole blood increased in all subjects and returned to preinfusion baseline values within 12 hours after cessation of the infusion. The mean half-life of nitrite estimated at maximal tolerated dose was 45.3 minutes for plasma and 51.4 minutes for whole blood. CONCLUSION: Sodium nitrite can be safely infused intravenously at defined concentrations for prolonged intervals. These results should be valuable for developing studies to investigate new NO treatment paradigms for a variety of clinical disorders, including cerebral vasospasm after subarachnoid hemorrhage, and ischemia of the heart, liver, kidney and brain, as well as organ transplants, blood-brain barrier modulation and pulmonary hypertension. CLINICAL TRIAL REGISTRATION INFORMATION: http://www.clinicaltrials.gov; NCT00103025

Gastro-Protective Effect of Fermented Soybean (Glycine max (L.) Merr.) in a Rat Model of Ethanol/HCl-Induced Gastric Injury

The present research purposed to examine the gastro-protective effect of Glycine max (L.) Merr. fermented using Lactobacillus delbrueckii ssp. delbrueckii Rosell-187 (Gastro-AD®) on ethanol/HCl-induced gastric damage, specifically on gastric acid secretion. After oral supplementation of Gastro-AD® to Sprague–Dawley (SD) rats with ethanol/HCl-induced gastric damage, we determined that Gastro-AD® attenuated the gastric mucosal lesion, hemorrhage and gastric acid secretion induced by ethanol/HCl. In addition, we observed that the Gastro-AD® treatment increased the serum prostaglandin E2 level and decreased the levels of gastric acid secretion-related receptors in both gastric tissues and primary gastric parietal cells. Furthermore, it decreased the levels of inflammatory factors, including serum histamine and expression of p-IκB, p-p65, iNOS and COX-2 and the activity of apoptotic signaling pathways, including those involving p-JNK, Bcl2/Bax, Fas, FADD, caspase-8 and caspase-3, in the stomach of the ethanol/HCl-treated rats. Thus, we suggest that Gastro-AD® supplementation may reduce ethanol/HCl-induced gastric acid secretion and prevent gastric injury

Feeding Ecology of Common Squid Todarodes pacificus in the South Sea of Korea Determined through Stable Isotope and Stomach Content Analyses

The common squid Todarodes pacificus is a dominant species within epipelagic communities and an important commercial species in the South and East seas of Korea and in the East China Sea. In this study, to examine the dietary composition, trophic position, and ontogenetic dietary shifts of the common squid, we analyzed stomach contents and stable isotope values (δ13C and δ15N) in muscle tissue across different body sizes (mantle length, ML) and seasons (winter, spring, and summer 2021) in the South Sea of Korea. Regardless of the season, the diet of the common squid predominantly comprised Pisces (37.9–94.0%) and Cephalopoda (6.0–61.0%). However, in the smallest individuals (ML < 10 cm), the stomach contents in August primarily comprised Crustacea (95.5%), thereby indicating a seasonal difference in dietary composition and ontogenetic dietary shifts only during summer. Similarly, our isotope results revealed seasonal isotopic variation among sampling periods and significant positive correlations between ML and both δ13C and δ15N values during the summer. These results reveal a seasonal variability in major diet components among the common squid of different size classes and that their feeding strategies are probably adjusted in response to the temporal availability of prey. Collectively, the findings of this study enhance our understanding of the feeding ecology of T. pacificus and thereby provide valuable information that will contribute to the ecological fishery management of this commercially important species

Feeding Ecology of Common Squid <i>Todarodes pacificus</i> in the South Sea of Korea Determined through Stable Isotope and Stomach Content Analyses

The common squid Todarodes pacificus is a dominant species within epipelagic communities and an important commercial species in the South and East seas of Korea and in the East China Sea. In this study, to examine the dietary composition, trophic position, and ontogenetic dietary shifts of the common squid, we analyzed stomach contents and stable isotope values (δ13C and δ15N) in muscle tissue across different body sizes (mantle length, ML) and seasons (winter, spring, and summer 2021) in the South Sea of Korea. Regardless of the season, the diet of the common squid predominantly comprised Pisces (37.9–94.0%) and Cephalopoda (6.0–61.0%). However, in the smallest individuals (ML 13C and δ15N values during the summer. These results reveal a seasonal variability in major diet components among the common squid of different size classes and that their feeding strategies are probably adjusted in response to the temporal availability of prey. Collectively, the findings of this study enhance our understanding of the feeding ecology of T. pacificus and thereby provide valuable information that will contribute to the ecological fishery management of this commercially important species

Lung‐ and liver‐dominant phenotypes of Korean eight constitution medicine have different profiles of genotype associated with each organ function

Abstract Eight Constitution Medicine (ECM), a ramification of traditional Korean medicine, has categorized people into eight constitutions. The main criteria of classification are inherited differences or predominance in the functions of organs, such as the liver or lung, diagnosed through ECM‐specific pulse patterns. This study investigated the association between single nucleotide polymorphism (SNP) genotypes and ECM phenotypes and explored candidate genetic makeups responsible for each constitution using a genome‐wide association study (GWAS). Sixty‐three healthy volunteers, who were either categorized as the Hepatonia (HEP, n = 32) or Pulmotonia (PUL, n = 31) constitution, were enrolled. HEP and PUL are two contrasting ECM types representing the dominant liver and lung phenotypes, respectively. SNPs were analyzed from the oral mucosa DNA using a commercially available microarray chip that can identify 820,000 SNPs. We conducted GWAS using logistic regression analysis and additive mode genotypes and constructed phylogenetic trees using the SNPhylo program with 8 SNPs specific for the liver phenotype and 15 SNPs for the lung phenotype. Although genome‐wide significant SNPs were not found, the phylogenetic tree showed a clear difference between the two constitutions. This is the first observation suggesting genetic involvement in the ECM and can be extended to all ECM constitutions

Increased Susceptibility of Mycobacterium tuberculosis to Ethionamide by Expressing PPs-Induced Rv0560c

Tuberculosis, an infectious disease, is one of the leading causes of death worldwide. Drug-resistant tuberculosis exacerbates its threat. Despite long-term and costly treatment with second-line drugs, treatment failure rates and mortality remain high. Therefore, new strategies for developing new drugs and improving the efficiency of existing drug treatments are urgently needed. Our research team reported that PPs, a new class of potential anti-tuberculosis drug candidates, can inhibit the growth of drug-resistant Mycobacterium tuberculosis. Here, we report a synergistic effect of PPs with ethionamide (ETH), one of the second-line drugs, as a result of further research on PPs. While investigating gene expression changes based on microarray and 2DE (two-dimensional gel electrophoresis), it was found that PPs induced the greatest overexpression of Rv0560c in M. tuberculosis. Based on this result, a protein microarray using Rv0560c protein was performed, and it was confirmed that Rv0560c had the highest interaction with EthR, a repressor for EthA involved in activating ETH. Accordingly, a synergistic experiment was conducted under the hypothesis of increased susceptibility of ETH to M. tuberculosis by PPs. As a result, in the presence of 0.5&times; MIC PPs, ETH showed a growth inhibitory effect on drug-sensitive and -resistant M. tuberculosis even at a much lower concentration of about 10-fold than the original MIC of ETH. It is also suggested that the effect was due to the interaction between PPs and Rv2887, the repressor of Rv0560c. This effect was also confirmed in a mouse model of pulmonary tuberculosis, confirming the potential of PPs as a booster to enhance the susceptibility of M. tuberculosis to ETH in treating drug-resistant tuberculosis. However, more in-depth mechanistic studies and extensive animal and clinical trials are needed in the future

Characteristics and Microbiome Profiling of Korean Gochang Bokbunja Vinegar by the Fermentation Process

As NGS (next-generation sequencing) technology develops, metagenomics-based microbial ecology, that is, microbiome research, has recently led to the science of fermented food. Based on the above technology, a study was conducted to understand the characteristics of vinegar made from bokbunja, a local crop in Gochang-gun, Korea. Physicochemical characteristics of vinegar, organic acid analysis, microbial community analysis, and electronic tongue analysis were explored while fermenting the vinegar for 70 days under eight fermentation conditions according to the concentration of bokbunja liquid (100% or 50%), type of fermenter (porcelain jar or stainless container), and fermentation environment (natural outdoor conditions or temperature/oxygen controlled). As a result, distinct microbial community patterns were found in the stage of acetic acid fermentation and, accordingly, this fermentation of Gochang vinegar is classified into three categories. Vinegar prepared by the traditional method of outdoor fermentation using jars showed characteristics of “Acetobacter (42.1%)/Lactobacillus (56.9%) fusion fermentation”. Under conditions where oxygen and temperature were controlled indoors using jars, characteristics of “Komagataeibacter (90.2%) fermentation” were found. “Lactobacillus (92.2%) fermentation” characteristics were discovered under natural outdoor conditions using stainless steel containers. These fermentation pattern differences were related to taxonomic phylogenetic diversity, which was also considered involved in determining organic acid production and taste. These results will be helpful as a scientific basis for understanding the fermentation characteristics of Gochang vinegar and developing high-value-added traditional vinegar products

The Effects of Iron Deficiency on the Gut Microbiota in Women of Childbearing Age

Iron deficiency anemia (IDA) is the most prevalent and common nutritional deficiency worldwide and is a global health problem with significant risk, particularly among women of reproductive age. Oral iron supplementation is the most widely used and cost-effective treatment for iron deficiency and IDA. However, there are limitations regarding side effects such as enteritis, treatment compliance, and bioavailability. Intestinal microbiome characteristic research has been recently conducted to overcome these issues, but more is needed. Against this background, a metagenomics study on the 16S gene in the feces of young women vulnerable to IDA was conducted. As a result of analyzing 16 normal subjects and 15 IDA patients, significant differences in bacterial community distribution were identified. In particular, a significant decrease in Faecalibacterium was characteristic in IDA patients compared with normal subjects. Furthermore, in the case of patients who recovered from IDA following iron supplementation treatment, it was confirmed that Faecalibacterium significantly recovered to normal levels. However, no significance in beta diversity was seen compared with before treatment. There were also no differences in the beta diversity results between the recovered and normal subjects. Therefore, intestinal dysbiosis during the disease state was considered to be restored as IDA improved. Although the results were derived from a limited number of subjects and additional research is needed, the results of this study are expected to be the basis for developing treatment and prevention strategies based on host&ndash;microbiome crosstalk in IDA