The exonuclease TREX1 constitutes an innate immune checkpoint limiting cGAS/STING-mediated antitumor immunity.

The DNA exonuclease TREX1 (Three-prime repair exonuclease 1) is critical for preventing autoimmunity in mice and humans by degrading endogenous cytosolic DNA, which otherwise triggers activation of the innate cGAS/STING pathway leading to the production of type I IFNs. Since tumor cells are prone to aberrant cytosolic DNA accumulation, we hypothesized that they are critically dependent on TREX1 activity to limit their immunogenicity. Here we show, that in tumor cells TREX1 indeed restricts the spontaneous activation of the cGAS/STING pathway and the subsequent induction of a type I IFN response. As a result, TREX1 deficiency compromised in vivo tumor growth in mice. This delay depended on a functional immune system, systemic type I IFN signaling, and tumor-intrinsic cGAS expression. Mechanistically, we show that tumor TREX1 loss drove activation of CD8 T cells and NK cells, prevented CD8 T cell exhaustion, and remodeled an immunosuppressive myeloid compartment. Consequently, TREX1 deficiency synergized with T cell-directed immune checkpoint blockade. Collectively, we conclude that TREX1 is essential to limit tumor immunogenicity, and that targeting this innate immune checkpoint remodels the tumor microenvironment and enhances anti-tumor immunity by itself and in combination with T cell-targeted therapies.

Comparative efficacies and safeties of cylindrical interstitial laser ablation and radiofrequency ablation on swine pancreas.

Laser ablation (LA) has been evaluated for the minimally invasive thermal treatment of various cancers, but conventional unidirectional endoscopic ultrasound (EUS)-guided LA has limitations. Therefore, we developed a cylindrical laser diffuser to overcome the limitations of unidirectional EUS-guided LA. The purpose of this study was to compare the efficacies and safeties of EUS-guided LA using a novel cylindrical laser diffuser and radiofrequency ablation (RFA) in vivo in swine pancreas. EUS-guided RFA (15 W, 30 s, 450 J) and cylindrical interstitial LA (CILA) (5 W, 90 s, 450 J) were applied to normal pancreatic tissue in six anesthetized pigs (three per group). Laboratory tests were performed at baseline, immediately after ablation (day 0), and 2 days after procedures (day 2). Two days after procedures, all pigs were sacrificed, and histopathological safety and efficacy assessments were performed. Technically, EUS-guided RFA and CILA were performed successfully in all cases. No major complications, including perforation or acute pancreatitis, occurred during the experiment in either group. All animals remained in excellent condition throughout the experimental period, and laboratory tests provided no evidence of a major complication. Average necrotic volumes in the RFA and CILA groups were 424.2 mm3 and 3747.4 mm3, respectively, and average necrotic volume was significantly larger in CILA group (p < 0.001). EUS-guided RFA and CILA had acceptable safety profiles in the normal swine pancreas model. Our findings indicate EUS-guided CILA has potential for the effective local treatment of pancreatic cancer as an alternative to EUS-guided RFA.

Angelica gigas extract inhibits acetylation of eNOS via IRE1α sulfonation/RIDD-SIRT1-mediated posttranslational modification in vascular dysfunction.

Angelica gigas NAKAI (AG) is a popular traditional medicinal herb widely used to treat dyslipidemia owing to its antioxidant activity. Vascular disease is intimately linked to obesity-induced metabolic syndrome, and AG extract (AGE) shows beneficial effects on obesity-associated vascular dysfunction. However, the effectiveness of AGE against obesity and its underlying mechanisms have not yet been extensively investigated. In this study, 40 high fat diet (HFD) rats were supplemented with 100-300 mg/kg/day of AGE to determine its efficacy in regulating vascular dysfunction. The vascular relaxation responses to acetylcholine were impaired in HFD rats, while the administration of AGE restored the diminished relaxation pattern. Endothelial dysfunction, including increased plaque area, accumulated reactive oxygen species, and decreased nitric oxide (NO) and endothelial nitric oxide synthase (eNOS) Ser1177 phosphorylation, were observed in HFD rats, whereas AGE reversed endothelial dysfunction and its associated biochemical signaling. Furthermore, AGE regulated endoplasmic reticulum (ER) stress and IRE1α sulfonation and its subsequent sirt1 RNA decay through controlling regulated IRE1α-dependent decay (RIDD) signaling, ultimately promoting NO bioavailability via the SIRT1-eNOS axis in aorta and endothelial cells. Independently, AGE enhanced AMPK phosphorylation, additionally stimulating SIRT1 and eNOS deacetylation and its associated NO bioavailability. Decursin, a prominent constituent of AGE, exhibited a similar effect in alleviating endothelial dysfunctions. These data suggest that AGE regulates dyslipidemia-associated vascular dysfunction by controlling ROS-associated ER stress responses, especially IRE1α-RIDD/sirt1 decay and the AMPK-SIRT1 axis.

Noncoding mutations cause super-enhancer retargeting resulting in protein synthesis dysregulation during B cell lymphoma progression.

Whole-genome sequencing of longitudinal tumor pairs representing transformation of follicular lymphoma to high-grade B cell lymphoma with MYC and BCL2 rearrangements (double-hit lymphoma) identified coding and noncoding genomic alterations acquired during lymphoma progression. Many of these transformation-associated alterations recurrently and focally occur at topologically associating domain resident regulatory DNA elements, including H3K4me3 promoter marks located within H3K27ac super-enhancer clusters in B cell non-Hodgkin lymphoma. One region found to undergo recurrent alteration upon transformation overlaps a super-enhancer affecting the expression of the PAX5/ZCCHC7 gene pair. ZCCHC7 encodes a subunit of the Trf4/5-Air1/2-Mtr4 polyadenylation-like complex and demonstrated copy number gain, chromosomal translocation and enhancer retargeting-mediated transcriptional upregulation upon lymphoma transformation. Consequently, lymphoma cells demonstrate nucleolar dysregulation via altered noncoding 5.8S ribosomal RNA processing. We find that a noncoding mutation acquired during lymphoma progression affects noncoding rRNA processing, thereby rewiring protein synthesis leading to oncogenic changes in the lymphoma proteome.

Clostridium difficile Bacteremia as a Rare Presentation of Polymicrobial Pyogenic Liver Abscesses and Its Management Challenges.

Extracolonic manifestations of Clostridium difficile have been rarely reported. We herein report a case of a 60-year-old immunocompetent man presenting with fever, nausea, abdominal pain, and loose stools for 2 weeks. Triple-phase liver computed tomography demonstrated pyogenic liver abscesses and portal pylephlebitis. Blood cultures grew C. difficile and Bacteroides fragilis, and liver abscess cultures grew Proteus mirabilis, Escherichia coli, and the viridans group Streptococci. Antibiotics coverage was selected to direct at all identified organisms. This demonstrates an unusual case of C. difficile bacteremia in a patient with polymicrobial pyogenic liver abscesses and pylephlebitis.

Lactobacillus helveticus Isolated from Raw Milk Improves Liver Function, Hepatic Steatosis, and Lipid Metabolism in Non-Alcoholic Fatty Liver Disease Mouse Model.

Here, we show that Lactiplantibacillus plantarum LP158 (LP158), Lactobacillus helveticus HY7804 (HY7804), and Lacticaseibacillus paracasei LPC226 (LPC226) isolated from raw milk alleviate non-alcoholic fatty acid disease (NAFLD) in a C57BL/6 mouse model. Lactic acid bacteria (LAB) were screened for their ability to inhibit fatty acid accumulation in palmitic acid (PA)-treated HepG2 cells, and three strains were selected based on the results. We also investigated hemolytic activity and antibiotic resistance of the three strains. LP158, HY7804, and LPC226 suppressed expression of mRNA encoding genes related to lipogenesis, and increased expression of genes related to ß-oxidation, in a PA-induced HepG2 cell model. Moreover, when LP158, HY7804, and LPC226 were administered at 109 CFU/kg/day for 8 weeks to mice with dietary-induced NAFLD, they all modulated blood biochemistry markers and reduced steatosis in liver tissue. Also, all three strains significantly reduced expression of mRNA encoding lipogenesis genes (Fasn, Acaca, and Srebp-1c) and inflammatory factors (Tnfα and Ccl-2) and fibrosis factors, and increased expression of a ß-oxidation gene (Acox1) in the liver. In particular, HY7804 showed the strongest effects both in vitro and in vivo. Therefore, HY7804, LP158, and LPC226 can be proposed as potential supplements that can improve NAFLD through anti-steatosis, anti-inflammatory, and anti-fibrotic effects.

Prognostic Impact of Minimal Pelvic Fluid in Locally Advanced Pancreatic Cancer: A Multicenter Retrospective Study.

BACKGROUND/AIMS: Minimal pelvic fluid (MPF) is occasionally encountered on computed tomography (CT) scans during the initial staging of newly diagnosed pancreatic cancer. However, its clinical relevance has scarcely been studied. This study intends to explore the incidence of minimal pelvic fluid and its relevance in terms of survival in locally advanced pancreatic cancer (LAPC) patients. MATERIALS AND METHODS: The medical records of patients with LAPC at 4 tertiary referral institutions were retrospectively reviewed from January 2005 to December 2015. Minimal pelvic fluid was defined as a fluid collection volume in the pelvic cavity of <100 mL as determined by abdominal CT. The association between the presence of MPF and patient survival was evaluated. RESULTS: A total of 59 patients (male:female, 33:26; median age, 68 years; range 46-82 years) with LAPC were enrolled. Of the 59 patients, 22.0% (n = 13) had MPF, and 78.0% (n = 46) had no pelvic fluid (NPF). Baseline clinical characteristics in the 2 groups, including extent of the tumor stage, extent of spread to the lymph nodes stage, and pattern of treatments, were not significantly different. However, median overall survival was significantly less in the MPF group [9.7 months, (95% CI, 5.9-13.5)] than in the NPF group as determined by the log-rank test [16.9 months, (95% CI, 9.3-24.5)] (P = .002), and univariate and multivariate analyses showed that the presence of MPF independently predicted a poor prognosis. CONCLUSION: The presence of MPF was found to be significantly associated with reduced survival and an independent poor prognostic biomarker in LAPC patients.

Location is a major barrier for transferring US fossil fuel employment to green jobs.

The green energy revolution may displace 1.7 million fossil fuel workers in the US but a Just Transition to emerging green industry jobs offers possibilities for re-employing these workers. Here, using 14 years of power plant data from the US Energy Information Administration, job transition data from the Census Bureau, as well as employment and skills data from the Bureau of Labor Statistics, we assess whether people employed in fossil fuel resource extraction today are co-located and have the transferable skills to switch to expected green jobs. We find that these workers could leverage their mobility to other industries and have similar skills to green occupations. However, today's fossil fuel extraction workers are not co-located with current sources of green energy production. Further, after accounting for federal employment projections, fossil fuel extraction workers are mostly not located in the regions where green employment will grow despite attaining the appropriate skillsets. These results suggest a large barrier to a Just Transition since fossil fuel extraction workers have not historically exhibited geospatial mobility. While stakeholders focus on re-skilling fossil fuel extraction workers, this analysis shows that co-location with emerging green employment will be the larger barrier to a Just Transition.

Tumor-intrinsic expression of the autophagy gene Atg16l1 suppresses anti-tumor immunity in colorectal cancer.

Microsatellite-stable colorectal cancer (MSS-CRC) is highly refractory to immunotherapy. Understanding tumor-intrinsic determinants of immunotherapy resistance is critical to improve MSS-CRC patient outcomes. Here, we demonstrate that high tumor expression of the core autophagy gene ATG16L1 is associated with poor clinical response to anti-PD-L1 therapy in KRAS-mutant tumors from IMblaze370 (NCT02788279), a large phase III clinical trial of atezolizumab (anti-PD-L1) in advanced metastatic MSS-CRC. Deletion of Atg16l1 in engineered murine colon cancer organoids inhibits tumor growth in primary (colon) and metastatic (liver and lung) niches in syngeneic female hosts, primarily due to increased sensitivity to IFN-γ-mediated immune pressure. ATG16L1 deficiency enhances programmed cell death of colon cancer organoids induced by IFN-γ and TNF, thus increasing their sensitivity to host immunity. In parallel, ATG16L1 deficiency reduces tumor stem-like populations in vivo independently of adaptive immune pressure. This work reveals autophagy as a clinically relevant mechanism of immune evasion and tumor fitness in MSS-CRC and provides a rationale for autophagy inhibition to boost immunotherapy responses in the clinic.

Machine learning based prediction for oncologic outcomes of renal cell carcinoma after surgery using Korean Renal Cell Carcinoma (KORCC) database.

We developed a novel prediction model for recurrence and survival in patients with localized renal cell carcinoma (RCC) after surgery and a novel statistical method of machine learning (ML) to improve accuracy in predicting outcomes using a large Asian nationwide dataset, updated KOrean Renal Cell Carcinoma (KORCC) database that covered data for a total of 10,068 patients who had received surgery for RCC. After data pre-processing, feature selection was performed with an elastic net. Nine variables for recurrence and 13 variables for survival were extracted from 206 variables. Synthetic minority oversampling technique (SMOTE) was used for the training data set to solve the imbalance problem. We applied the most of existing ML algorithms introduced so far to evaluate the performance. We also performed subgroup analysis according to the histologic type. Diagnostic performances of all prediction models achieved high accuracy (range, 0.77-0.94) and F1-score (range, 0.77-0.97) in all tested metrics. In an external validation set, high accuracy and F1-score were well maintained in both recurrence and survival. In subgroup analysis of both clear and non-clear cell type RCC group, we also found a good prediction performance.

Bactericidal Effect of Underwater Plasma Treatment on Waste Brine from Kimchi Production Process and the Evaluation of Reusability of Plasma-Treated Waste Brine in Salting Kimchi Cabbage.

Recycling waste brine from the Kimchi production process is an important environmental and industry issue. We applied an underwater plasma to reduce food-borne pathogens in the waste brine. The capillary electrodes supplied by alternating current (AC) bi-polar pulsed power were applied to treat 100 L of waste brine. The inactivation efficacy was analyzed using four different agars (Tryptic Soy Agar (TSA), Marine agar (MA), de Man Rogosa Sharpe Agar (MRS), and Yeast Extract-Peptone-Dextrose (YPD), respectively. The microbial population was reduced linearly with treatment time, irrespective of culturing medium. The inactivation followed the log-linear model (R2: 0.96-0.99). The reusability of plasma-treated waste brine (PTWB) was determined by five parameters (salinity, pH, acidity, reducing sugar, and the population of microorganisms) of salted Kimchi cabbage, and they were compared with newly made brine (NMB) and waste brine (WB), respectively. The results showed that the quality of salted Kimchi cabbage prepared by PTWB was not significantly different from that of NMB, indicating that the underwater plasma treatment is feasible to reuse waste brine in the salting process of Kimchi production.

Endoscopic Ultrasound-Guided Pancreatic Interstitial Laser Ablation Using a Cylindrical Laser Diffuser: A Long-Term Follow-Up Study.

BACKGROUND AND AIMS: Local ablative treatment is another option for improving outcomes and has been evaluated for locally advanced pancreatic cancer. We previously suggested endoscopic ultrasound (EUS)-guided interstitial laser ablation using a cylindrical laser diffuser (CILA) might be a feasible therapeutic option based on experiments performed on pancreatic cancer cell lines and porcine model with a short follow-up (3 days). The aim of this study was to investigate the safety of EUS-CILA performed using optimal settings in porcine pancreas with a long-term follow-up (2 weeks). METHODS: EUS-CILA (laser energy of 450 J; 5 W for 90 s) was applied to normal pancreatic tissue in porcine (n = 5) under EUS guidance. Animals were observed clinically for 2 weeks after EUS-CILA to evaluate complications. Computed tomography and laboratory tests were carried out to evaluate safety. Two weeks after EUS-CILA, all pigs were sacrificed, and histopathological safety and efficacy evaluations were conducted. RESULTS: EUS-CILA was technically successful in all five cases. No major complications occurred during the follow-up period. Body weight of porcine did not change during the study period without any significant change in feed intake. Animals remained in excellent condition throughout the experimental period, and laboratory tests and computed tomography (CT) scans provided no evidence of a major complication. Histopathological evaluation showed complete ablation in the ablated area with clear delineation of surrounding normal pancreatic tissue. Mean ablated volume was 55.5 mm2 × 29.0 mm and mean ablated areas in the pancreatic sections of the five pigs were not significantly different (p = 0.368). CONCLUSIONS: In conclusion, our experimental study suggests that EUS-CILA is safe and has the potential to be an effective local treatment modality. No major morbidity or mortality occurred during the study period. Further evaluations are warranted before clinical application.

Semantic Segmentation of Pancreatic Cancer in Endoscopic Ultrasound Images Using Deep Learning Approach.

Endoscopic ultrasonography (EUS) plays an important role in diagnosing pancreatic cancer. Surgical therapy is critical to pancreatic cancer survival and can be planned properly, with the characteristics of the target cancer determined. The physical characteristics of the pancreatic cancer, such as size, location, and shape, can be determined by semantic segmentation of EUS images. This study proposes a deep learning approach for the segmentation of pancreatic cancer in EUS images. EUS images were acquired from 150 patients diagnosed with pancreatic cancer. A network with deep attention features (DAF-Net) is proposed for pancreatic cancer segmentation using EUS images. The performance of the deep learning models (U-Net, Attention U-Net, and DAF-Net) was evaluated by 5-fold cross-validation. For the evaluation metrics, the Dice similarity coefficient (DSC), intersection over union (IoU), receiver operating characteristic (ROC) curve, and area under the curve (AUC) were chosen. Statistical analysis was performed for different stages and locations of the cancer. DAF-Net demonstrated superior segmentation performance for the DSC, IoU, AUC, sensitivity, specificity, and precision with scores of 82.8%, 72.3%, 92.7%, 89.0%, 98.1%, and 85.1%, respectively. The proposed deep learning approach can provide accurate segmentation of pancreatic cancer in EUS images and can effectively assist in the planning of surgical therapies.

Effect of a Proton Pump Inhibitor on the Duodenum Microbiome of Gastric Ulcer Patients.

The gut microbiota are regarded as a functional organ that plays a substantial role in human health and disease. Proton pump inhibitors (PPIs) are widely used in medicine but can induce changes in the overall gut microbiome and cause disease-associated dysbiosis. The microbiome of the duodenum has not been sufficiently studied, and the effects of PPIs on the duodenal microbiome are poorly understood. In this study, we investigated the effect of PPI administration on duodenum microbiota in patients with a gastric ulcer. A total of 12 gastric ulcer patients were included, and PPI (Ilaprazole, Noltec®, 10 mg) was prescribed in all patients for 4 weeks. A total of 17 samples from the second portion of the duodenum were analyzed. Microbiome compositions were assessed by sequencing the V3-V4 region of the 16s rRNA gene (Miseq). Changes in microbiota compositions after 4 weeks of PPI treatment were analyzed. a-Diversity was higher after PPI treatment (p = 0.02, at Chao1 index), and ß-diversity was significantly different after treatment (p = 0.007). Welch's t-test was used to investigate changes in phyla, genus, and species level, and the abundance of Akkermansia muciniphila, belonging to the phylum Verrucomicrobia, and Porphyromonas endodontalis, belonging to the phylum Bacteroidetes, was significantly increased after treatment (p = 0.044 and 0.05). PPI administration appears to induce duodenal microbiome dysbiosis while healing gastric ulcers. Further large-scale studies on the effects of PPIs on the duodenal microbiome are required.

Esophagitis after Clozapine Use in a 61-Year-Old Woman with Refractory Schizophrenia.

Clozapine-induced esophagitis has been rarely reported. We herein report a case of a 61-year-old woman with schizophrenia who developed hematemesis, fever, and tachycardia after the initiation of clozapine. An esophagogastroduodenoscopy showed esophageal mucosal ulcerations. Her gastrointestinal symptoms resolved with pantoprazole, allowing continuation of her clozapine treatment. We report here an unusual association of severe esophagitis with clozapine use.

Natural alleles of CIRCADIAN CLOCK ASSOCIATED1 contribute to rice cultivation by fine-tuning flowering time.

The timing of flowering is a crucial factor for successful grain production at a wide range of latitudes. Domestication of rice (Oryza sativa) included selection for natural alleles of flowering-time genes that allow rice plants to adapt to broad geographic areas. Here, we describe the role of natural alleles of CIRCADIAN CLOCK ASSOCIATED1 (OsCCA1) in cultivated rice based on analysis of single-nucleotide polymorphisms deposited in the International Rice Genebank Collection Information System database. Rice varieties harboring japonica-type OsCCA1 alleles (OsCCA1a haplotype) flowered earlier than those harboring indica-type OsCCA1 alleles (OsCCA1d haplotype). In the japonica cultivar "Dongjin", a T-DNA insertion in OsCCA1a resulted in late flowering under long-day and short-day conditions, indicating that OsCCA1 is a floral inducer. Reverse transcription quantitative PCR analysis showed that the loss of OsCCA1a function induces the expression of the floral repressors PSEUDO-RESPONSE REGULATOR 37 (OsPRR37) and Days to Heading 8 (DTH8), followed by repression of the Early heading date 1 (Ehd1)-Heading date 3a (Hd3a)-RICE FLOWERING LOCUS T 1 (RFT1) pathway. Binding affinity assays indicated that OsCCA1 binds to the promoter regions of OsPRR37 and DTH8. Naturally occurring OsCCA1 alleles are evolutionarily conserved in cultivated rice (O. sativa). Oryza rufipogon-I (Or-I) and Or-III type accessions, representing the ancestors of O. sativa indica and japonica, harbored indica- and japonica-type OsCCA1 alleles, respectively. Taken together, our results demonstrate that OsCCA1 is a likely domestication locus that has contributed to the geographic adaptation and expansion of cultivated rice.

Identification of RNA-DNA Hybrids Associated with R-Loops at the IgH Switch Sequence in Activated B Cells.

During transcription and replication, R-loops that contain RNA-DNA hybrids are generated across numerous genomic loci and contribute to many biological events. Using S9.6, a monoclonal antibody against RNA-DNA hybrids, accelerated the study of R-loop biology. An outpouring of recent studies has implicated various contributions of R-loop in physiological cellular functions. Earlier studies using nondenaturing sodium bisulfite probing also supported existence of DNA-RNA hybrids formation in mammalian cells. In activated B cells, RNA-DNA hybrids formation at IgH gene locus of B cells is crucial for class switch recombination that ensure the proper effector function of the antibody. Here, we describe the identification of R-loops associated with the IgH locus using RNA-DNA hybrid immunoprecipitation sequencing and nondenaturing sodium bisulfite probing. This will be helpful for future studies of R-loops status on whole genome as well as on IgH locus in B cells.

RNA exosome drives early B cell development via noncoding RNA processing mechanisms.

B cell development is linked to successful V(D)J recombination, allowing B cell receptor expression and ultimately antibody secretion for adaptive immunity. Germline noncoding RNAs (ncRNAs) are produced at immunoglobulin (Ig) loci during V(D)J recombination, but their function and posttranscriptional regulation are incompletely understood. Patients with trichohepatoenteric syndrome, characterized by RNA exosome pathway component mutations, exhibit lymphopenia, thus demonstrating the importance of ncRNA surveillance in B cell development in humans. To understand the role of RNA exosome in early B cell development in greater detail, we generated mouse models harboring a B cell-specific cre allele (Mb1cre), coupled to conditional inversion-deletion alleles of one RNA exosome core component (Exosc3) or RNase catalytic subunits (Exosc10 or Dis3). We noticed increased expression of RNA exosome subunits during V(D)J recombination, whereas a B cell developmental blockade at the pro-B cell stage was observed in the different knockout mice, overlapping with a lack of productive rearrangements of VDJ genes at the Ig heavy chain (Igh). This unsuccessful recombination prevented differentiation into pre-B cells, with accumulation of ncRNAs and up-regulation of the p53 pathway. Introduction of a prearranged Igh VDJ allele partly rescued the pre-B cell population in Dis3-deficient cells, although V-J recombination defects were observed at Ig light chain kappa (Igκ), preventing subsequent B cell development. These observations demonstrated that the RNA exosome complex is important for Igh and Igκ recombination and establish the relevance of RNA processing for optimal diversification at these loci during B cell development.

The Effect of Gap Distance between a Pin and Water Surface on the Inactivation of Escherichia coli Using a Pin-to-Water Plasma.

Atmospheric plasmas have been applied for the inactivation of microorganisms. Industrials demand to investigate the relation of the key reactive species induced by plasmas and the operating parameters including boundary conditions in order to control plasma treatment processes. In this study, we investigated the effect of gap distance between a pin-electrode and water surface on inactivation efficacy. When the gap distance decreased from 5 mm to 1 mm, the reduction of Escherichia coli (E. coli) was increased to more than 4 log CFU/mL. The reactive oxygen species measured optically and spectrophotometrically were influenced by gap distance. The results from electron spin resonance (ESR) analysis showed that the pin-to-water plasma generated hydroxyl radical (OH•) and singlet oxygen (1O2) in the water and superoxide radical (O2-•) served as a precursor of OH•. The inactivation of E. coli was significantly alleviated by sodium azide (1O2 scavenger), indicating that 1O2 contributes the most to bacterial inactivation. These findings provide a potentially effective strategy for bacterial inactivation using a pin-to-water plasma.

Anti-Diabetic Effects of Allium hookeri Extracts Prepared by Different Methods in Type 2 C57BL/J-db/db Mice.

This study was conducted to evaluate whether Allium hookeri can control diabetic symptoms. Aqueous extract (AE1: 100 mg/kg BW, AE2: 200 mg/kg BW) and ethanol extract (EE1: 100 mg/kg BW, EE2: 200 mg/kg BW) of A. hookeri were orally administrated to diabetic mice (C57BL/J-db/db) for 8 weeks. The negative (NC) and the positive (PC) control groups were treated with 0.9% saline and metformin (150 mg/kg BW), respectively. Glucose and lipid profile (triglyceride, total cholesterol (TC), LDL-C, and HDL-C) as biochemical parameters, toxicological factors such as liver/kidney functional parameters (ALT, AST, BUN, and Cr), and NK cell activity in blood were measured. Oral glucose tolerance test (OGTT) and histopathological examination were also conducted. Compared with the NC group, AE and EE decreased blood glucose, HbA1c, area under the curve (AUC) during OGTT, and leptin levels while increasing adiponectin levels. Serum lipid profiles and toxicological factors levels were reduced by the A. hookeri extract. Interestingly, HDL-C, glomerular mesangial expansion score in the kidney, and NK cell activity were effectively controlled in EE groups. Based on the results, EE is considered to be more effective in reducing high blood glucose, lipid profile, and related factor levels than AE, and is comparable to metformin in some biomarkers. It can be presumed that EE can more effectively control the major anomalies in the diabetic model than AE, and it may be used to prevent diabetic symptoms without toxicity in the Type 2 diabetic model.