RAS/RAF mutations and microsatellite instability status in primary colorectal cancers according to HER2 amplification.

HER2 amplification-associated molecular alterations and clinicopathologic features in colorectal cancers (CRCs) have not been well established. In this study, we assessed the prevalence of HER2 amplification and microsatellite instability (MSI) status of 992 patients with primary CRC. In addition, molecular alterations of HER2 amplified and unamplified CRCs were examined and compared by next-generation sequencing. HER2 amplifications were found in 41 (4.1%) of 992 primary CRCs. HER2 amplification was identified in 1.0% of the right colonic tumors, 5.1% of the left colonic tumors, and 4.8% of the rectal tumors. Approximately 95% of HER2 amplification was observed in the left colon and rectum. Seven (87.5%) of eight metastatic tumors showed HER2 amplification. Most clinicopathologic features were unrelated to HER2 amplification except tumor size and MSI status. All 41 HER2 amplified CRCs were microsatellite stable. In a molecular analysis of frequently identified somatic mutations in CRCs, HER2 amplified CRCs showed a lower rate of KRAS mutations (24.4%) but a higher rate of TP53 mutations (83%) than unamplified CRCs. No BRAF and NRAS mutations were identified in HER2 amplified CRCs. Our study suggests that HER2 amplified CRCs are mutually exclusive of MSI and harbor less frequent KRAS/NRAS/BRAF mutations but frequent T53 mutations.

Carbon dioxide valorization into resveratrol via lithoautotrophic fermentation using engineered Cupriavidus necator H16.

BACKGROUND: Industrial biomanufacturing of value-added products using CO2 as a carbon source is considered more sustainable, cost-effective and resource-efficient than using common carbohydrate feedstocks. Cupriavidus necator H16 is a representative H2-oxidizing lithoautotrophic bacterium that can be utilized to valorize CO2 into valuable chemicals and has recently gained much attention as a promising platform host for versatile C1-based biomanufacturing. Since this microbial platform is genetically tractable and has a high-flux carbon storage pathway, it has been engineered to produce a variety of valuable compounds from renewable carbon sources. In this study, the bacterium was engineered to produce resveratrol autotrophically using an artificial phenylpropanoid pathway. RESULTS: The heterologous genes involved in the resveratrol biosynthetic pathway-tyrosine ammonia lyase (TAL), 4-coumaroyl CoA ligase (4CL), and stilbene synthase (STS) -were implemented in C. necator H16. The overexpression of acetyl-CoA carboxylase (ACC), disruption of the PHB synthetic pathway, and an increase in the copy number of STS genes enhanced resveratrol production. In particular, the increased copies of VvSTS derived from Vitis vinifera resulted a 2-fold improvement in resveratrol synthesis from fructose. The final engineered CR-5 strain produced 1.9 mg/L of resveratrol from CO2 and tyrosine via lithoautotrophic fermentation. CONCLUSIONS: To the best of our knowledge, this study is the first to describe the valorization of CO2 into polyphenolic compounds by engineering a phenylpropanoid pathway using the lithoautotrophic bacterium C. necator H16, demonstrating the potential of this strain a platform for sustainable chemical production.

Tailored polyhydroxyalkanoate production from renewable non-fatty acid carbon sources using engineered Cupriavidus necator H16.

As thermoplastic, nontoxic, and biocompatible polyesters, polyhydroxyalkanoates (PHAs) are considered promising biodegradable plastic candidates for diverse applications. Short-chain-length/medium-chain-length (SCL/MCL) PHA copolymers are flexible and versatile PHAs that are typically produced from fatty acids, which are expensive and toxic. Therefore, to achieve the sustainable biosynthesis of SCL/MCL-PHAs from renewable non-fatty acid carbon sources (e.g., sugar or CO2), we used the lithoautotrophic bacterium Cupriavidus necator H16 as a microbial platform. Specifically, we synthesized tailored PHA copolymers with varying MCL-3-hydroxyalkanoate (3HA) compositions (10-70 mol%) from fructose by rewiring the MCL-3HA biosynthetic pathways, including (i) the thioesterase-mediated free fatty acid biosynthetic pathway coupled with the beta-oxidation cycle and (ii) the hydroxyacyl transferase-mediated fatty acid de novo biosynthetic pathway. In addition to sugar-based feedstocks, engineered strains are also promising platforms for the lithoautotrophic production of SCL/MCL-PHAs from CO2. The set of engineered C. necator strains developed in this study provides greater opportunities to produce customized polymers with controllable monomer compositions from renewable resources.

Biotechnological Plastic Degradation and Valorization Using Systems Metabolic Engineering.

Various kinds of plastics have been developed over the past century, vastly improving the quality of life. However, the indiscriminate production and irresponsible management of plastics have led to the accumulation of plastic waste, emerging as a pressing environmental concern. To establish a clean and sustainable plastic economy, plastic recycling becomes imperative to mitigate resource depletion and replace non-eco-friendly processes, such as incineration. Although chemical and mechanical recycling technologies exist, the prevalence of composite plastics in product manufacturing complicates recycling efforts. In recent years, the biodegradation of plastics using enzymes and microorganisms has been reported, opening a new possibility for biotechnological plastic degradation and bio-upcycling. This review provides an overview of microbial strains capable of degrading various plastics, highlighting key enzymes and their role. In addition, recent advances in plastic waste valorization technology based on systems metabolic engineering are explored in detail. Finally, future perspectives on systems metabolic engineering strategies to develop a circular plastic bioeconomy are discussed.

Enhanced production of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) with modulated 3-hydroxyvalerate fraction by overexpressing acetolactate synthase in Cupriavidus necator H16.

The elastomeric properties of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), a biodegradable copolymer, strongly depend on the molar composition of 3-hydroxyvalerate (3HV). This paper reports an improved artificial pathway for enhancing the 3HV component during PHBV biosynthesis from a structurally unrelated carbon source by Cupriavidus necator H16. To increase the intracellular accumulation of propionyl-CoA, a key precursor of the 3HV monomer, we developed a recombinant strain by genetically manipulating the branched-chain amino acid (e.g., valine, isoleucine) pathways. Overexpression of the heterologous feedback-resistant acetolactate synthase (alsS), (R)-citramalate synthase (leuA), homologous 3-ketothiolase (bktB), and the deletion of 2-methylcitrate synthase (prpC) resulted in biosynthesis of 42.5 % (g PHBV/g dry cell weight) PHBV with 64.9 mol% 3HV monomer from fructose as the sole carbon source. This recombinant strain also accumulated the highest PHBV content of 54.5 % dry cell weight (DCW) with 24 mol% 3HV monomer from CO2 ever reported. The lithoautotrophic cell growth and PHBV production by the recombinant C. necator were promoted by oxygen stress. The thermal properties of PHBV showed a decreasing trend of the glass transition and melting temperatures with increasing 3HV fraction. The average molecular weights of PHBV with modulated 3HV fractions were between 20 and 26 × 104 g/mol.

Data-driven approach to predicting the risk of pressure injury: A retrospective analysis based on changes in patient conditions.

AIMS: To determine the risk of pressure injury development in the intensive care unit based on changes in patient conditions. DESIGN: This retrospective study was based on secondary data analysis. METHODS: Patient data from electronic health records were retrospectively obtained and we included 438 and 1752 patients with and without pressure injury, respectively, among those admitted to the medical and surgical intensive care units (ICUs) from January 2017-February 2020. Changes in patient conditions were analysed based on the first and last objective data values from the day of ICU admission to the day before the onset of pressure injury and categorised as follows: improved, maintained normal, exacerbated and unchanged. Logistic regression was performed to identify the significant predictors of pressure injury development based on 11 variables. RESULTS: The 11 selected variables were age, body mass index, activity, acute physiology and chronic health evaluation II score, nursing severity level, pulse and albumin, haematocrit, C-reactive protein, total bilirubin and blood urea nitrogen levels. The risk for a pressure injury was high with exacerbation of or persistently abnormal levels of nursing severity, albumin, haematocrit, C-reactive protein, blood urea nitrogen and pulse >100 beat/min. CONCLUSION: Periodic monitoring of haematological variables is important for preventing pressure injury in the intensive care unit. REPORTING METHOD: The study followed STROBE guidelines. PATIENT OR PUBLIC CONTRIBUTION: This study contributes to the utilisation of patient data from electronic health records. RELEVANCE TO CLINICAL PRACTICE: In addition to other pressure injury risk assessment tools, ICU nurses can help prevent pressure injuries by assessing patients' blood test results, thereby promoting patient safety and enhancing the efficacy of nursing practice.

Effective hexanol production from carbon monoxide using extractive fermentation with Clostridium carboxidivorans P7.

This study achieved high production of hexanol via gas fermentation using Clostridium carboxidivorans P7 by extracting hexanol from the fermentation broth. The hexanol extraction efficiency and inhibitory effects on C. carboxidivorans P7 of 2-butyl-1-octanol, hexyl hexanoate and oleyl alcohol were examined, and oleyl alcohol was selected as the extraction solvent. Oleyl alcohol was added at the beginning of fermentation and during fermentation or a small volume of oleyl alcohol was repeatedly added during fermentation. The addition of a small volume of oleyl alcohol during fermentation was the most effective for CO consumption and hexanol production (5.06 g/L), yielding the highest known hexanol titer through any type of fermentation including gas fermentation. Hexanol production was further enhanced to 8.45 g/L with the repeated addition of oleyl alcohol and ethanol during gas fermentation. The results of this study will enable sustainable and carbon-neutral hexanol production via gas fermentation.

Patient Factors That Influence Reliable Delirium Assessments in a Medical Intensive Care Unit During the Routine Clinical Practice.

This study aimed to determine patient and therapeutic characteristics of patients in the medical intensive care unit (MICU) that contribute to inconsistent results of delirium assessments performed during routine clinical practice. Therefore, electronic health records were reviewed and compared with secondary data collected from the same medical ICU patients who were assessed using the Confusion Assessment Method in the ICU (CAM-ICU). Of 5,241 cases involving 762 patients, 827 (15.78%) cases showed disagreement between assessments. Continuous renal replacement therapy, physical restraint use, and altered mental status were factors that increased the likelihood of inconsistencies between assessments. A significant positive correlation was found between the CAM-ICU disagreement rate and the total number of assessments per month. To maximize the reliability of delirium assessments, individual-targeted approaches considering the patient's level of consciousness and type of treatment implemented are required, along with ensuring a stable, and regulated working environment and customized educational programs.

Engineering Cupriavidus necator H16 for enhanced lithoautotrophic poly(3-hydroxybutyrate) production from CO2.

BACKGROUND: A representative hydrogen-oxidizing bacterium Cupriavidus necator H16 has attracted much attention as hosts to recycle carbon dioxide (CO2) into a biodegradable polymer, poly(R)-3-hydroxybutyrate (PHB). Although C. necator H16 has been used as a model PHB producer, the PHB production rate from CO2 is still too low for commercialization. RESULTS: Here, we engineer the carbon fixation metabolism to improve CO2 utilization and increase PHB production. We explore the possibilities to enhance the lithoautotrophic cell growth and PHB production by introducing additional copies of transcriptional regulators involved in Calvin Benson Bassham (CBB) cycle. Both cbbR and regA-overexpressing strains showed the positive phenotypes for 11% increased biomass accumulation and 28% increased PHB production. The transcriptional changes of key genes involved in CO2-fixing metabolism and PHB production were investigated. CONCLUSIONS: The global transcriptional regulator RegA plays an important role in the regulation of carbon fixation and shows the possibility to improve autotrophic cell growth and PHB accumulation by increasing its expression level. This work represents another step forward in better understanding and improving the lithoautotrophic PHB production by C. necator H16.

Factors associated with self-care behavior in patients with pre-dialysis or dialysis-dependent chronic kidney disease.

Self-care behavior plays a pivotal role in the management of chronic kidney disease. Improved self-care behavior in patients with chronic kidney disease is a key factor in health management and treatment adherence. This study aimed to evaluate the participants' general and medical condition-related characteristics, physiological indices and the level of health literacy affecting self-care behavior in patients with chronic kidney disease in South Korea. The data of 278 participants were analyzed using t-test, analysis of variance, correlation coefficient, and linear multiple regression analysis. There were significant differences in self-care behavior scores depending on participants' age and cohabitation status, employment, and smoking status as well as having dialysis due to end-stage kidney disease; number of comorbidities; levels of serum hemoglobin, calcium, and creatinine; and estimated glomerular filtration rate. The results of regression analysis revealed that not currently working, non-smoker, end-stage kidney disease, and positive response to the "actively managing my health" scale of the Health Literacy Questionnaire significantly affected self-care behavior in patients with chronic kidney disease, and the explanatory power of the model was 32.7%. Therefore, it is necessary to identify each patient's barriers or needs according to individual characteristics, such as age, cohabitation and employment status, and daily life circumstances, including smoking habits, comorbidities, social support, and level of health literacy to develop efficient support strategies for promoting adequate self-care behavior with CKD.

Enhanced tolerance of Cupriavidus necator NCIMB 11599 to lignocellulosic derived inhibitors by inserting NAD salvage pathway genes.

Polyhydroxybutyrate (PHB) is a bio-based, biodegradable and biocompatible plastic that has the potential to replace petroleum-based plastics. Lignocellulosic biomass is a promising feedstock for industrial fermentation to produce bioproducts such as polyhydroxybutyrate (PHB). However, the pretreatment processes of lignocellulosic biomass lead to the generation of toxic byproducts, such as furfural, 5-HMF, vanillin, and acetate, which affect microbial growth and productivity. In this study, to reduce furfural toxicity during PHB production from lignocellulosic hydrolysates, we genetically engineered Cupriavidus necator NCIMB 11599, by inserting the nicotine amide salvage pathway genes pncB and nadE to increase the NAD(P)H pool. We found that the expression of pncB was the most effective in improving tolerance to inhibitors, cell growth, PHB production and sugar consumption rate. In addition, the engineered strain harboring pncB showed higher PHB production using lignocellulosic hydrolysates than the wild-type strain. Therefore, the application of NAD salvage pathway genes improves the tolerance of Cupriavidus necator to lignocellulosic-derived inhibitors and should be used to optimize PHB production.

Production of Hexanol as the Main Product Through Syngas Fermentation by Clostridium carboxidivorans P7.

The production of hexanol from syngas by acetogens has gained attention as a replacement for petroleum-derived hexanol, which is widely used in the chemical synthesis and plastic industries. However, acetogenic bacteria generally produce C2 compounds (e.g., acetate and ethanol) as the main products. In this study, the gas fermentation conditions favorable for hexanol production were investigated at different temperatures (30-37°C) and CO gas contents (30-70%) in batch gas fermentation. Hexanol production increased from 0.02 to 0.09 g/L when the cultivation temperature was lowered from 37 to 30°C. As the CO content increased from 30 to 70%, the CO consumption rate and hexanol production (yield, titer, and ratio of C6 compound to total products) increased with the CO content. When 70% CO gas was repeatedly provided by flushing the headspace of the bottles at 30°C, the total alcohol production increased to 4.32 g/L at the expense of acids. Notably, hexanol production (1.90 g/L) was higher than that of ethanol (1.20 g/L) and butanol (1.20 g/L); this is the highest level of hexanol produced in gas fermentation to date and the first report of hexanol as the main product. Hexanol production was further enhanced to 2.34 g/L when 2 g/L ethanol was supplemented at the beginning of 70% CO gas refeeding fermentation. Particularly, hexanol productivity was significantly enhanced to 0.18 g/L/day while the supplemented ethanol was consumed, indicating that the conversion of ethanol to acetyl-CoA and reducing equivalents positively affected hexanol production. These optimized culture conditions (gas fermentation at 30°C and refeeding with 70% CO gas) and ethanol supplementation provide an effective and sustainable approach for bio-hexanol production.

Improving Lipid Production of Yarrowia lipolytica by the Aldehyde Dehydrogenase-Mediated Furfural Detoxification.

Yarrowia lipolytica, the non-conventional yeast capable of high lipogenesis, is a microbial chassis for producing lipid-based biofuels and chemicals from renewable resources such as lignocellulosic biomass. However, the low tolerance of Y. lipolytica against furfural, a major inhibitory furan aldehyde derived from the pretreatment processes of lignocellulosic biomass, has restricted the efficient conversion of lignocellulosic hydrolysates. In this study, the furfural tolerance of Y. lipolytica has been improved by supporting its endogenous detoxification mechanism. Specifically, the endogenous genes encoding the aldehyde dehydrogenase family proteins were overexpressed in Y. lipolytica to support the conversion of furfural to furoic acid. Among them, YALI0E15400p (FALDH2) has shown the highest conversion rate of furfural to furoic acid and resulted in two-fold increased cell growth and lipid production in the presence of 0.4 g/L of furfural. To our knowledge, this is the first report to identify the native furfural detoxification mechanism and increase furfural resistance through rational engineering in Y. lipolytica. Overall, these results will improve the potential of Y. lipolytica to produce lipids and other value-added chemicals from a carbon-neutral feedstock of lignocellulosic biomass.

Finding of novel polyhydroxybutyrate producer Loktanella sp. SM43 capable of balanced utilization of glucose and xylose from lignocellulosic biomass.

Polyhydroxybutyrate (PHB) is a potential substitute for plastics derived from fossil fuels, owing to its biodegradable and biocompatible properties. Lignocellulosic biomass could be used to reduce PHB production costs; however, the co-utilization of sugars, such as glucose and xylose, without catabolite repression is a difficult problem to be solved. Here, we selected a novel Loktanella sp. SM43 from a marine environment and optimized the conditions for PHB production. Loktanella sp. SM43 showed high PHB production (66.5% content) from glucose. When glucose and xylose were used together, this strain showed high utilization of both substrates compared to other high PHB-producers such as Halomonas sp. and Cupriavidus necator, which showed glucose preference. Loktanella sp. SM43 showed high growth and PHB production with lignocellulosic hydrolysates. When pine tree hydrolysates were used, PHB production was the highest at 3.66 ± 0.01 g/L, followed by Miscanthus (3.46 ± 0.09 g/L) and barley straw hydrolysate (3.36 ± 0.36 g/L). Overall, these results reveal the potential of Loktanella sp. SM43 to produce PHB using various lignocellulosic hydrolysates as feedstock and the first systematic study for PHB production with Loktanella sp. The approach of screening novel strains is a strategy to overcome co-utilization of sugars without genetic engineering.

Glucose/Xylose Co-Fermenting Saccharomyces cerevisiae Increases the Production of Acetyl-CoA Derived n-Butanol From Lignocellulosic Biomass.

Efficient xylose catabolism in engineered Saccharomyces cerevisiae enables more economical lignocellulosic biorefinery with improved production yields per unit of biomass. Yet, the product profile of glucose/xylose co-fermenting S. cerevisiae is mainly limited to bioethanol and a few other chemicals. Here, we introduced an n-butanol-biosynthesis pathway into a glucose/xylose co-fermenting S. cerevisiae strain (XUSEA) to evaluate its potential on the production of acetyl-CoA derived products. Higher n-butanol production of glucose/xylose co-fermenting strain was explained by the transcriptomic landscape, which revealed strongly increased acetyl-CoA and NADPH pools when compared to a glucose fermenting wild-type strain. The acetate supplementation expected to support acetyl-CoA pool further increased n-butanol production, which was also validated during the fermentation of lignocellulosic hydrolysates containing acetate. Our findings imply the feasibility of lignocellulosic biorefinery for producing fuels and chemicals derived from a key intermediate of acetyl-CoA through glucose/xylose co-fermentation.

Using Electroencephalogram Biosignal Changes for Delirium Detection in Intensive Care Units.

ABSTRACT: BACKGROUND: Biosignal data acquired during quantitative electroencephalography (QEEG) research may ultimately be used to develop algorithms for more accurate detection of delirium. This study investigates the biosignal changes during delirium states by using the QEEG data of patients in a medical intensive care unit. METHODS: This observational study was conducted between September 2018 and December 2019 at a tertiary hospital in South Korea. Delirium was measured using the Korean version of Confusion Assessment Method for the Intensive Care Unit in intensive care unit patients. Quantitative EEG measurements were recorded for 20 minutes in a natural state without external treatment or stimuli, and QEEG data measured in the centroparietal and parietal regions with eyes open were selected for analysis. Power spectrum analysis with a 5-minute epoch was conducted on the selected 65 cases. RESULTS: QEEG changes in the presence of delirium indicated that alpha, beta, gamma, and spectral edge frequency 50% waves showed significantly lower absolute power spectra than the corresponding findings in the absence of delirium. Brain-mapping results showed that these brain waves were inactivated in delirious states. CONCLUSION: QEEG assessments can potentially detect the changes in the centroparietal and parietal regions of delirium patients. QEEG changes, including lower power spectra of alpha, beta, and gamma waves, and spectral edge frequency 50%, can be successfully used to distinguish delirium from the absence of delirium.

Metabolic engineering for the utilization of carbohydrate portions of lignocellulosic biomass.

The petrochemical industry has grown to meet the need for massive production of energy and commodities along with an explosive population growth; however, serious side effects such as greenhouse gas emissions and global warming have negatively impacted the environment. Lignocellulosic biomass with myriad quantities on Earth is an attractive resource for the production of carbon-neutral fuels and chemicals through environmentally friendly processes of microbial fermentation. This review discusses metabolic engineering efforts to achieve economically feasible industrial production of fuels and chemicals from microbial cell factories using the carbohydrate portion of lignocellulosic biomass as substrates. The combined knowledge of systems biology and metabolic engineering has been applied to construct robust platform microorganisms with maximum conversion of monomeric sugars, such as glucose and xylose, derived from lignocellulosic biomass. By comprehensively revisiting carbon conversion pathways, we provide a rationale for engineering strategies, as well as their features, feasibility, and recent representative studies. In addition, we briefly discuss how tools in systems biology can be applied in the field of metabolic engineering to accelerate the development of microbial cell factories that convert lignocellulosic biomass into carbon-neutral fuels and chemicals with economic feasibility.

Synthesis and structure-activity relationship studies of 1,5-isomers of triazole-pyrrolopyrimidine as selective Janus kinase 1 (JAK1) inhibitors.

JAK inhibitors have been considered as useful targets for the treatment of related diseases. However, first-generation JAK inhibitors have side effects such as anemia, thrombocytopenia, neutropenia and headaches which have been suggested to result from high JAK2 inhibition. Second-generation JAK inhibitors with more specific JAK isozyme inhibition have been studied to eliminate these adverse effects. In this study, novel 4-(1,5- or 2,5-triazole)-pyrrolopyrimidine derivatives with aromatic moieties were synthesized as JAK1 inhibitors, and an in vitro enzyme assay was used to evaluate the JAK inhibitory effects. Among these JAK1 inhibitors, the compound 23a showed an IC50 level of 72 nM, as well as being selective against other JAKs by 12 times or more: the results of molecular docking studies suggested that the high JAK1 selectivity resulted from a key interaction between the iodine atom of compound 23a and His-885 of hJAK1.

Therapeutic Potential of Sitafloxacin as a New Drug Candidate for Helicobacter Eradication in Korea: An In Vitro Culture-Based Study.

BACKGROUND: Increased prevalence of antibiotic resistance to Helicobacter pylori (H. pylori) infection worldwide has driven the search for a new therapeutic candidate. Recently, sitafloxacin, a novel 4-quinolone agent, has emerged as a new therapeutic option for H. pylori eradication, in Japan. However, data on its efficacy for H. pylori eradication in Korea are limited. Therefore, we aimed to investigate the therapeutic potential of sitafloxacin as a first-line treatment for patients with Helicobacter infection through gastric tissue culture-based studies. MATERIALS AND METHODS: We prospectively enrolled treatment-naïve patients with H. pylori infection who visited the Gil Medical Center between March 2015 and March 2018. After obtaining written informed consent from patients, a total of 121 H. pylori strains were collected. We tested the susceptibility of these strains to sitafloxacin, and other antibiotics for Helicobacter eradication, including clarithromycin (CLR), metronidazole (MTZ), amoxicillin (AMX), tetracycline (TET), levofloxacin (LEV), and ciprofloxacin (CIP) using the agar dilution technique. The minimum inhibitory concentration (MIC) of these antibiotics against H. pylori strains were determined. RESULTS: None of the H. pylori strains obtained were resistant to sitafloxacin (MIC > 1, n = 0), while other conventional eradication drugs including CLR, MTZ, AMX, and TET showed 24.8% (n = 30), 30.6% (n = 37), 5.0% (n = 6), and 0.8% (n = 1) resistance, respectively. Compared to the resistance rates of other quinolones (LEV [36.4%, n = 44] and CIP [37.2%, n = 45]), sitafloxacin showed the best antibiotic performance against Helicobacter strains (0%, n = 0). Furthermore, sitafloxacin also inhibited the growth of 14 H. pylori strains (12.4%), which were resistant to both of clarithromycin, and metronidazole, and 27 strains (22.3%) with multidrug resistance. CONCLUSIONS: Sitafloxacin might be a new promising candidate for Helicobacter eradication where antibiotic resistance for Helicobacter is an emerging medical burden, such as in Korea.

Mitochondrial DNA Haplogroup Related to the Prevalence of Helicobacter pylori.

Mitochondria are essential organelles that are not only responsible for energy production but are also involved in cell metabolism, calcium homeostasis, and apoptosis. Targeting mitochondria is a key strategy for bacteria to subvert host cells' physiology and promote infection. Helicobacter (H.) pylori targets mitochondria directly. However, mitochondrial genome (mtDNA) polymorphism (haplogroup) is not yet considered an important factor for H. pylori infection. Here, we clarified the association of mitochondrial haplogroups with H. pylori prevalence and the ability to perform damage. Seven mtDNA haplogroups were identified among 28 H. pylori-positive subjects. Haplogroup B was present at a higher frequency and haplotype D at a lower one in the H. pylori population than in that of the H. pylori-negative one. The fibroblasts carrying high-frequency haplogroup displayed a higher apoptotic rate and diminished mitochondrial respiration following H. pylori infection. mtDNA mutations were accumulated more in the H. pylori-positive population than in that of the H. pylori-negative one in old age. Among the mutations, 57% were located in RNA genes or nonsynonymous protein-coding regions in the H. pylori-positive population, while 35% were in the H. pylori-negative one. We concluded that gastric disease caused by Helicobacter virulence could be associated with haplogroups and mtDNA mutations.