Profiling of endogenous metabolites and changes in intestinal microbiota distribution after GEN-001 (Lactococcus lactis) administration.

This study aimed to identify metabolic biomarkers and investigate changes in intestinal microbiota in the feces of healthy participants following administration of Lactococcus lactis GEN-001. GEN-001 is a single-strain L. lactis strain isolated from the gut of a healthy human volunteer. The study was conducted as a parallel, randomized, phase 1, open design trial. Twenty healthy Korean males were divided into five groups according to the GEN-001 dosage and dietary control. Groups A, B, C, and D1 received 1, 3, 6, and 9 GEN-001 capsules (1 × 1011 colony forming units), respectively, without dietary adjustment, whereas group D2 received 9 GEN-001 capsules with dietary adjustment. All groups received a single dose. Fecal samples were collected 2 days before GEN-001 administration to 7 days after for untargeted metabolomics and gut microbial metagenomic analyses; blood samples were collected simultaneously for immunogenicity analysis. Levels of phenylalanine, tyrosine, cholic acid, deoxycholic acid, and tryptophan were significantly increased at 5-6 days after GEN-001 administration when compared with predose levels. Compared with predose, the relative abundance (%) of Parabacteroides and Alistipes significantly decreased, whereas that of Lactobacillus and Lactococcus increased; Lactobacillus and tryptophan levels were negatively correlated. A single administration of GEN-001 shifted the gut microbiota in healthy volunteers to a more balanced state as evidenced by an increased abundance of beneficial bacteria, including Lactobacillus, and higher levels of the metabolites that have immunogenic properties.

LI-RADS Category on MRI Is Associated With Recurrence of Intrahepatic Cholangiocarcinoma After Surgery: A Multicenter Study.

BACKGROUND: The Liver Imaging Reporting and Data System (LI-RADS) is a comprehensive system for standardizing the terminology and interpretation of liver imaging. The association between the LI-RADS category and tumor recurrence in patients with intrahepatic cholangiocarcinomas (iCCAs) has not yet been evaluated in a multicenter study. PURPOSE: To retrospectively investigate the preoperative clinical and imaging features associated with recurrence-free survival (RFS) after curative resection of iCCAs and to identify the role of the LI-RADS category in at-risk patients. STUDY TYPE: Retrospective, multicenter. SUBJECTS: A total of 113 patients (mean age: 61.1 years; 74 men, 39 women) who underwent preoperative contrast-enhanced MRI and curative surgical resection for a single treatment-naive iCCA between 2008 and 2021. FILED STRENGTH/SEQUENCE: A 3 T dual gradient-echo T1 WI with in- and opposed-phase, turbo spin-echo T2 WI, diffusion-weighted echo-planar images, and three-dimensional gradient-echo T1 WI before and after administration of contrast agent. ASSESSMENT: MR imaging features were evaluated and assigned for each lesion using LI-RADS version 2018. RFS was calculated from the date of surgery to tumor recurrence or the last imaging date without evidence of recurrence. Factors affecting RFS were evaluated using clinical and imaging features. STATISTICAL TESTS: Cox proportional hazards model, Kaplan-Meier method, and log-rank test. A P-value of <0.05 was considered statistically significant. RESULTS: A total of 93 (82.3%) were categorized as LR-M and 20 (17.7%) were categorized as LR-4 or 5. In the multivariable analysis, LR-M category (hazard ratio [HR], 8.035; 95% confidence interval [CI], 1.096-58.931) and a tumor size >3 cm on MRI (HR, 2.690; 95% CI, 1.319-5.487) were independent factors for poor RFS. The 5-year RFS rate was significantly higher in patients with iCCA categorized as LR-4 or 5 than in those categorized as LR-M (94.4% vs. 51.9%, respectively). DATA CONCLUSION: Patients with iCCA categorized as LR-4 or 5 may have a better RFS than those categorized as LR-M. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

Semi-quantitative estimation of cellular SiO2 nanoparticles using flow cytometry combined with X-ray fluorescence measurements.

In this study, we have demonstrated feasibility of a semi-quantitative approach for the estimation of cellular SiO2 nanoparticles (NPs), which is based on the flow cytometry measurements of their normalized side scattering intensity. In order to improve our understanding on the quantitative aspects of cell-nanoparticle interactions, flow cytometry, transmission electron microscopy, and X-ray fluorescence experiments were carefully performed for the HeLa cells exposed to SiO2 NPs with different core diameters, hydrodynamic sizes, and surface charges. Based on the observed relationships among the experimental data, a semi-quantitative cellular SiO2 NPs estimation method from their normalized side scattering and core diameters was proposed, which can be applied for the determination of cellular SiO2 NPs within their size-dependent linear ranges.

Metabolomic Profiles in Patients with Cervical Cancer Undergoing Cisplatin and Radiation Therapy.

This study was aimed to evaluate endogenous metabolic changes before and after cisplatin and radiation therapy in patients with cervical cancer via untargeted metabolomic analysis using plasma samples. A total of 13 cervical cancer patients were enrolled in this study. Plasma samples were collected from each patient on two occasions: approximately one week before therapy (P1) and after completion of cisplatin and radiation therapy (P2). Of the 13 patients, 12 patients received both cisplatin and radiation therapy, whereas one patient received radiation therapy alone. The samples were analyzed using the Ultimate 3000 coupled with Q ExactiveTM Focus Hybrid Quadrupole-OrbitrapTM mass spectrometry (Thermo Fisher Scientific, Waltham, MA, USA). Chromatographic separation utilized a Kinetex C18 column 2.1×100 mm (2.6 µm) (Phenomenex, Torrance, CA, USA), and the temperature was maintained at 40°C. Following P2, there were statistically significant increases in the concentrations of indoxyl sulfate, phenylacetylglutamine, Lysophosphatidyethanolamine (LysoPE) (18:1), and indole-3-acetic acid compared with the concentrations observed at P1. Specifically, in the human papillomavirus (HPV) noninfection group, indoxyl sulfate, LysoPE (18:1), and phenylacetylglutamine showed statistically significant increases at P2 compared with P1. No significant changes in metabolite concentrations were observed in the HPV infection group. Indoxyl sulfate, LysoPE (18:1), phenylacetylglutamine, and indole-3-acetic acid were significantly increased following cisplatin and radiation therapy.

Practice guidelines for managing extrahepatic biliary tract cancers.

Backgrounds/Aims: Reported incidence of extrahepatic bile duct cancer is higher in Asians than in Western populations. Korea, in particular, is one of the countries with the highest incidence rates of extrahepatic bile duct cancer in the world. Although research and innovative therapeutic modalities for extrahepatic bile duct cancer are emerging, clinical guidelines are currently unavailable in Korea. The Korean Society of Hepato-Biliary-Pancreatic Surgery in collaboration with related societies (Korean Pancreatic and Biliary Surgery Society, Korean Society of Abdominal Radiology, Korean Society of Medical Oncology, Korean Society of Radiation Oncology, Korean Society of Pathologists, and Korean Society of Nuclear Medicine) decided to establish clinical guideline for extrahepatic bile duct cancer in June 2021. Methods: Contents of the guidelines were developed through subgroup meetings for each key question and a preliminary draft was finalized through a Clinical Guidelines Committee workshop. Results: In November 2021, the finalized draft was presented for public scrutiny during a formal hearing. Conclusions: The extrahepatic guideline committee believed that this guideline could be helpful in the treatment of patients.

Effect of Inhalation of Aromatherapy Oil on Patients with Perennial Allergic Rhinitis: A Randomized Controlled Trial.

This study aimed to investigate the effects of aromatherapy oil inhalation on symptoms, quality of life, sleep quality, and fatigue level among adults with perennial allergic rhinitis (PAR). Fifty-four men and women aged between 20 and 60 were randomized to inhale aromatherapy oil containing essential oil from sandalwood, geranium, and Ravensara or almond oil (the placebo) for 5 minutes twice daily for 7 days. PAR symptoms determined by Total Nasal Symptom Score (TNSS), the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), sleep quality by Verran Synder-Halpern (VSH) scale, and fatigue level by Chalder Fatigue Scale (CFS) were assessed before and after intervention period. Compared with the placebo, the experimental group showed significant improvement in TNSS, especially in nasal obstruction. The aromatherapy group also showed significantly higher improvements in total score of RQLQ and CFS. These findings indicate that inhalation of certain aromatherapy oil helps relieve PAR symptoms, improve rhinitis-specific quality of life, and reduce fatigue in patients with PAR. In conclusion, inhalation of aromatherapy essential oil may have potential as an effective intervention to alleviate PAR.

Corrigendum to "Effect of Inhalation of Aromatherapy Oil on Patients with Perennial Allergic Rhinitis: A Randomized Controlled Trial".

[This corrects the article DOI: 10.1155/2016/7896081.].

Effects of Inhalation of Essential Oil of Citrus aurantium L. var. amara on Menopausal Symptoms, Stress, and Estrogen in Postmenopausal Women: A Randomized Controlled Trial.

This study aimed to investigate the effects of inhalation of the essential oil of Citrus aurantium L. var. amara (neroli oil) on menopausal symptoms, stress, and estrogen in postmenopausal women. Sixty-three healthy postmenopausal women were randomized to inhale 0.1% or 0.5% neroli oil or almond oil (control) for 5 minutes twice daily for 5 days. Menopause-related symptoms, as determined by the Menopause-Specific Quality of Life Questionnaire (MENQOL); sexual desire visual analog scale (VAS); serum cortisol and estrogen concentrations, blood pressure, pulse, and stress VAS, were measured before and after inhalation. Compared with the control group, the two neroli oil groups showed significant improvements in the physical domain score of the MENQOL and in sexual desire. Systolic blood pressure was significantly lower in the group inhaling 0.5% neroli oil than in the control group. Compared with the control group, the two neroli oil groups showed significantly lower diastolic blood pressure and tended to improve pulse rate and serum cortisol and estrogen concentrations. These findings indicate that inhalation of neroli oil helps relieve menopausal symptoms, increase sexual desire, and reduce blood pressure in postmenopausal women. Neroli oil may have potential as an effective intervention to reduce stress and improve the endocrine system.

Effects of surface-modifying ligands on the colloidal stability of ZnO nanoparticle dispersions in in vitro cytotoxicity test media.

The extrinsic physicochemical properties of nanoparticles (NPs), such as hydrodynamic size, surface charge, surface functional group, and colloidal stabilities, in toxicity testing media are known to have a significant influence on in vitro toxicity assessments. Therefore, interpretation of nanotoxicity test results should be based on reliable characterization of the NPs' extrinsic properties in actual toxicity testing media. Here, we present a set of physicochemical characterization results for commercially available ZnO NPs, including core diameter, hydrodynamic diameter, surface charges, and colloidal stabilities, in two in vitro toxicity testing media (Roswell Park Memorial Institute [RPMI] and Dulbecco's Modified Eagle's Medium [DMEM]), as well as simple cell viability assay results for selected ZnO NPs. Four commercially available and manufactured ZnO NPs, with different core sizes, were used in this study, and their surface charge was modified with five different surface coating materials (sodium citrate, tris(2-aminoethyl)amine, poly(acrylic acid), poly(allylamine hydrochloride), and poly-L-lysine hydrochloride). The results showed that ZnO NPs were better dispersed in cell culture media via surface modification with positively or negatively charged molecules. Moreover, in the presence of fetal bovine serum (FBS) in RPMI and DMEM media, ZnO NPs were found even better dispersed for a longer period (at least 48 hours). For the HeLa cells exposed to ZnO NPs in DMEM media without FBS, surface charge-dependent cytotoxicity trends were observed, while these trends were not observed for those cells cultured in FBS-containing media. This confirmed the important roles of surface-modifying compounds and of surface charge on the resultant cytotoxicities of NPs.

Automated genome-wide visual profiling of cellular proteins involved in HIV infection.

Recent genome-wide RNAi screens have identified >842 human genes that affect the human immunodeficiency virus (HIV) cycle. The list of genes implicated in infection differs between screens, and there is minimal overlap. A reason for this variance is the interdependence of HIV infection and host cell function, producing a multitude of indirect or pleiotropic cellular effects affecting the viral infection during RNAi screening. To overcome this, the authors devised a 15-dimensional phenotypic profile to define the viral infection block induced by CD4 silencing in HeLa cells. They demonstrate that this phenotypic profile excludes nonspecific, RNAi-based side effects and viral replication defects mediated by silencing of housekeeping genes. To achieve statistical robustness, the authors used automatically annotated RNAi arrays for seven independent genome-wide RNAi screens. This identified 56 host genes, which reliably reproduced CD4-like phenotypes upon HIV infection. The factors include 11 known HIV interactors and 45 factors previously not associated with HIV infection. As proof of concept, the authors confirmed that silencing of PAK1, Ku70, and RNAseH2A impaired HIV replication in Jurkat cells. In summary, multidimensional, visual profiling can identify genes required for HIV infection.

Visual genome-wide RNAi screening to identify human host factors required for Trypanosoma cruzi infection.

The protozoan parasite Trypanosoma cruzi is the etiologic agent of Chagas disease, a neglected tropical infection that affects millions of people in the Americas. Current chemotherapy relies on only two drugs that have limited efficacy and considerable side effects. Therefore, the development of new and more effective drugs is of paramount importance. Although some host cellular factors that play a role in T. cruzi infection have been uncovered, the molecular requirements for intracellular parasite growth and persistence are still not well understood. To further study these host-parasite interactions and identify human host factors required for T. cruzi infection, we performed a genome-wide RNAi screen using cellular microarrays of a printed siRNA library that spanned the whole human genome. The screening was reproduced 6 times and a customized algorithm was used to select as hits those genes whose silencing visually impaired parasite infection. The 162 strongest hits were subjected to a secondary screening and subsequently validated in two different cell lines. Among the fourteen hits confirmed, we recognized some cellular membrane proteins that might function as cell receptors for parasite entry and others that may be related to calcium release triggered by parasites during cell invasion. In addition, two of the hits are related to the TGF-beta signaling pathway, whose inhibition is already known to diminish levels of T. cruzi infection. This study represents a significant step toward unveiling the key molecular requirements for host cell invasion and revealing new potential targets for antiparasitic therapy.