Characterization of the intestinal transport mechanism of polystyrene microplastics (MPs) and the potential inhibitory effect of green tea extracts on MPs intestinal absorption.

The aims of the current study included characterizing the intestinal transport mechanism of polystyrene microplastics (MPs) with different charges and sizes in the intestinal epithelial cell model and determining the inhibitory effect of green tea extracts (GTEs) on the intestinal absorption of MPs in Caco-2 cells. The smaller sizes, which included diameters of 0.2 µm, of amine-modified MPs compared to either larger size (1 µm diameter, or carboxylate-MPs (0.2 and 1 µm diameter) significantly lowered the cell viability of caco-2 cells that were measured by MTT assay (p < 0.05). The transported amount (particles/mL of the cell media) of amine-modified MPs by the Caco-2 cell, was not dependent according to the concentrations, energy, or temperature, but it was higher than the carboxylate-modified MPs. The co-treatment of GTEs with the amine-modified MPs inhibited Caco-2 cell cytotoxicity as well as reduced the production of intracellular reactive oxygen species (ROS) in HepG2 generated by the exposure of amine-modified MPs. The GTEs co-treatment also increased trans-epithelial electrical resistances (TEER) and reduced the transportation of Lucifer Yellow via the Caco-2 monolayer compared to only the amine-modified MPs exposure. The GTEs treatment led to a decrease in the number of amine-modified MPs transported to the basal side of the Caco-2 monolayer. The results from our study suggest that the consumption of GTEs could enhance the intestinal barrier function by recovering intestinal epithelial cell damage induced by MPs, which resulted in a decrease of the intestinal absorption of MPs.

Efficient Plant Regeneration System from Leaf Explant Cultures of Daphne genkwa via Somatic Embryogenesis.

This study aimed to establish an efficient plant regeneration system from leaf-derived embryogenic structure cultures of Daphne genkwa. To induce embryogenic structures, fully expanded leaf explants of D. genkwa were cultured on Murashige and Skoog (MS) medium supplemented with 0, 0.1, 0.5, 1, 2, and 5 mg·L-1 2,4-dichlorophenoxyacetic acid (2,4-D), respectively. After 8 weeks of incubation, the highest frequency of embryogenic structure formation reached 100% when the leaf explants were cultivated on MS medium supplemented with 0.1 to 1 mg·L-1 2,4-D. At higher concentrations of 2,4-D (over 2 mg·L-1 2,4-D), the frequency of embryogenic structure formation significantly declined. Similar to 2,4-D, indole butyric acid (IBA) and α-naphthaleneacetic acid (NAA) treatments were also able to form embryogenic structures. However, the frequency of embryogenic structure formation was lower than that of 2,4-D. In particular, the yellow embryonic structure (YES) and white embryonic structure (WES) were simultaneously developed from the leaf explants of D. genkwa on culture medium containing 2,4-D, IBA, and NAA, respectively. Embryogenic calluses (ECs) were formed from the YES after subsequent rounds of subculture on MS medium supplemented with 1 mg·L-1 2,4-D. To regenerate whole plants, the embryogenic callus (EC) and the two embryogenic structures (YES and WES) were transferred onto MS medium supplemented with 0.1 mg·L-1 6-benzyl aminopurine (BA). The YES had the highest plant regeneration potential via somatic embryo and shoot development compared to the EC and WES. To our knowledge, this is the first successful report of a plant regeneration system via the somatic embryogenesis of D. genkwa. Thus, the embryogenic structures and plant regeneration system of D. genkwa could be applied to mass proliferation and genetic modification for pharmaceutical metabolite production in D. genkwa.

Red Ginseng Dietary Fiber Shows Prebiotic Potential by Modulating Gut Microbiota in Dogs.

Red ginseng, widely used in traditional medicine for various conditions, imparts health benefits mainly by modulating the gut microbiota in humans. Given the similarities in gut microbiota between humans and dogs, red ginseng-derived dietary fiber may have prebiotic potential in dogs; however, its effects on the gut microbiota in dogs remain elusive. This double-blinded, longitudinal study investigated the impact of red ginseng dietary fiber on the gut microbiota and host response in dogs. A total of 40 healthy household dogs were randomly assigned to low-dose (n = 12), high-dose (n = 16), or control (n = 12) groups and fed a normal diet supplemented with red ginseng dietary fiber (3 g/5 kg body weight per day, 8 g/5 kg per day, or no supplement, respectively) for 8 weeks. The gut microbiota of the dogs was analyzed at 4 weeks and 8 weeks using 16S rRNA gene sequencing of fecal samples. Alpha diversity was significantly increased at 8 and 4 weeks in the low-dose and high-dose groups, respectively. Moreover, biomarker analysis showed that short-chain fatty acid producers such as Sarcina and Proteiniclasticum were significantly enriched, while potential pathogens such as Helicobacter were significantly decreased, indicating the increased gut health and pathogen resistance by red ginseng dietary fiber. Microbial network analysis showed that the complexity of microbial interactions was increased by both doses, indicating the increased stability of the gut microbiota. These findings suggest that red ginseng-derived dietary fiber could be used as a prebiotic to modulate gut microbiota and improve gut health in dogs. IMPORTANCE The canine gut microbiota is an attractive model for translational studies, as it responds to dietary interventions similarly to those in humans. Investigating the gut microbiota of household dogs that share the environment with humans can produce highly generalizable and reproducible results owing to their representativeness of the general canine population. This double-blind and longitudinal study investigated the impact of dietary fiber derived from red ginseng on the gut microbiota of household dogs. Red ginseng dietary fiber altered the canine gut microbiota by increasing diversity, enriching short-chain fatty acid-producing microbes, decreasing potential pathogens, and increasing the complexity of microbial interactions. These findings indicate that red ginseng-derived dietary fiber may promote canine gut health by modulating gut microbiota, suggesting the possibility of its use as a potential prebiotic.

Anti-Periodontitis Effects of Dendropanax morbiferus H.Lév Leaf Extract on Ligature-Induced Periodontitis in Rats.

Periodontitis is caused by pathogens in the oral cavity. It is a chronic infectious disease that causes symptoms including gingival bleeding and tooth loss resulting from the destruction of periodontal tissues coupled with inflammation. Dendropanax morbiferus H.Lév (DM) is a natural product that exhibits various biological activities with few side effects. In this study, the potential of DM leaf hot-water extracts (DMWE) as a treatment for periodontitis was determined and its anti-oxidant and anti-inflammatory effects were evaluated. Compounds in DMWE were identified by high-performance liquid chromatography (HPLC) and nitric oxide (NO) and prostaglandin E2 (PGE2) production was measured in RAW 264.7 cells. We measured the gingival index and gingival sulcus depth, and micro-CT was performed in vivo using a ligature-induced periodontitis rat model, which is similar to human periodontitis. The DMWE-treated group exhibited a decrease in cytokine concentration and relieved the gingival index and gingival sulcus depth compared with the periodontitis-induced control group. In addition, micro-CT and histological analysis revealed that DMWE exhibited anti-inflammatory effects and improved alveolar bone loss in periodontitis-induced rats. These findings suggest that DMWE has excellent anti-oxidant and anti-inflammatory effects that protect and prevent periodontal tissue damage and tooth loss caused by the inflammatory response.

CGV: Cancer Genome Viewer, a web service for integrative cancer genome and pharmacogenomic data analysis.

MOTIVATION: Multi-omic profiling data, such as The Cancer Genome Atlas and pharmacogenomic data, facilitate research into cancer mechanisms and drug development. However, it is not easy for researchers to connect, integrate and analyze huge and heterogeneous data, which is a major obstacle to the utilization of cancer genomic data. RESULTS: We developed Cancer Genome Viewer (CGV), a user-friendly web service that provides functions to integrate and visualize cancer genome data and pharmacogenomic data. Users can easily select and customize the samples to be analyzed with the pre-defined selection options for patients' clinic-pathological features from multiple datasets. Using the customized dataset, users can perform subsequent data analyses comprehensively, including gene set analysis, clustering or survival analysis. CGV also provides pre-calculated drug response scores from pharmacogenomic data, which may facilitate the discovery of new cancer targets and therapeutics. AVAILABILITY AND IMPLEMENTATION: CGV web service is implemented with the R Shiny application at http://cgv.sysmed.kr and the source code is freely available at https://git.sysmed.kr/sysmed_public/cgv. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Mechanism of protein tyrosine phosphatase 1B inhibition by theaflavanoside IV isolated from methanolic extract of tea (Camellia sinensis) seed shells.

Camellia sinensis (tea) seeds have been identified as potential sources of nutraceutical compounds. In this study, caffeine and theaflavanoside IV were annotated as the most abundant phytochemicals in the seed shells of C. sinensis. Both compound displayed potent inhibitions against protein tyrosine phosphatase 1B (PTP1B) with IC50 values of 37.9 ± 3.5 and 8.7 ± 1.1 µM, respectively. In the kinetic study, caffeine inhibited PTP1B with mixed type I mode, which prefers to bind to free enzyme. Theaflavanoside IV showed competitive and reversible simple slow-binding inhibition [k3 = 0.1 µM-1·min-1, k4 = 0.002 min-1, Kiapp = 0.0002 µM]. This is the first report on PTP1B-inhibitory activity of these compounds and their action mechanisms. These results suggest their potential in the development of antidiabetic agents.

Management of Small Nonfunctioning Pancreatic Neuroendocrine Neoplasms: Current Opinion and Controversies.

The incidence of small and asymptomatic pancreatic neuroendocrine neoplasms (PNENs) has increased due to the widespread use of high-resolution diagnostic imaging in screening programs. Most PNENs are slow-growing indolent neoplasms. However, a local invasion or metastasis can sometimes occur with PNENs, leading to a poor prognosis. The management of small, nonfunctioning PNENs remains under debate. The National Comprehensive Cancer Network guidelines recommend observation in selected cases of small PNENs less than 2 cm. Pancreatic surgery remains a high-risk operation with a 28-30% morbidity and 1% mortality. Therefore, the decision on how to manage small PNENs is challenging. This review focuses on the management of small nonfunctioning PNENs. We also highlight the malignant potential of small PNENs according to tumor size, tumor grade, and tumor biomarker. Endoscopic-ultrasound-guided biopsy is recommended to evaluate the potential risk of malignancy. Furthermore, we discuss the current guidelines and future directions for the management of small PNENs.

Effect of Characterized Green Tea Extraction Methods and Formulations on Enzymatic Starch Hydrolysis and Intestinal Glucose Transport.

The purpose of the current study was to investigate the effect of various characterized green tea extracts (GTEs) according to extraction methods on enzymatic starch hydrolysis and intestinal glucose transport. Codigestion of wheat starch with water extract (WGT) or ethanol extract formulated with green tea polysaccharides and flavonols (CATEPLUS) produced 3.4-3.5 times higher resistant starch (RS) than wheat starch only. Its microstructures were changed to spherical shapes and smooth surfaces as shown by scanning electron microscopy (SEM) results. According to Fourier transform infrared (FT-IR) spectra, the absorption peak of O-H stretching was red-shifted in WGT or CATEPLUS. The results confirmed that hydrogen bonds were formed between starch granules and polysaccharides in WGT or CATEPLUS. Intestinal glucose transport subsequently measured after in vitro digestion was mostly suppressed in CATEPLUS. Gene expression of the glucose transporter protein, particularly SGLT1, was significantly inhibited by addition of CATEPLUS (p < 0.05). Results from the current study suggest that co-intake of green tea extracts formulated with green tea polysaccharides and flavonols could be a potentially useful means to delay blood glucose absorption when consuming starchy foods.

Diagnostic value of diffusion-weighted brain magnetic resonance imaging in patients with sporadic Creutzfeldt-Jakob disease: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the diagnostic yield and performance of DWI in patients with sporadic CJD (sCJD). METHODS: A systematic literature search of the MEDLINE and EMBASE databases was performed, since their inception up to July 28, 2020. Pooled diagnostic yield of diffusion-weighted imaging was calculated using DerSimonian-Laird random-effects model. Pooled diagnostic performance of DWI (sensitivity, specificity, and area under the curve) in diagnosing sCJD among patients with rapidly progressive dementia was calculated using a bivariate random-effects model. Subgroup analysis and meta-regression were performed. RESULTS: Fifteen original articles with a total of 1144 patients with sCJD were included. The pooled diagnostic yield was 91% (95% confidence interval [CI], 86 to 94%); summary sensitivity, 91% (95% CI, 84 to 95%); and specificity, 97% (95% CI, 94 to 99%). The area under the hierarchical summary receiver operating characteristic curve was 0.99 (95% CI, 0.97-0.99). Simultaneous involvement of the neocortex and striatum was the most common finding, and the neocortex was the most common site to be involved on DWI followed by striatum, thalamus, and cerebellum. Subgroup analysis and meta-regression demonstrated significant heterogeneity among the studies associated with the reference standards used for diagnosis of sCJD. CONCLUSIONS: DWI showed excellent diagnostic value in diagnosis of sporadic Creutzfeldt-Jakob disease among patients with rapidly progressive dementia. Simultaneous involvement of the neocortex and striatum was the most common finding, and the neocortex was the most common site to be involved on diffusion-weighted imaging followed by striatum, thalamus, and cerebellum. KEY POINTS: • The pooled diagnostic yield of diffusion-weighted imaging in sporadic Creutzfeldt-Jakob disease was 91%. • The diagnostic performance of diffusion-weighted imaging for predicting sporadic Creutzfeldt-Jakob disease among patients with rapidly progressive dementia was excellent, with pooled sensitivity, 91%, and specificity, 97%. • Simultaneous involvement in the neocortex and striatum was most commonly seen on diffusion-weighted imaging (60%), followed by the neocortex without striatum (30%), thalamus (21%), cerebellum (8%), and striatum without neocortex (7%).

Malignant potential of small pancreatic neuroendocrine neoplasm and its risk factors: A multicenter nationwide study.

BACKGROUND: Pancreatic neuroendocrine neoplasms (PNENs) show heterogeneous biological behavior, and most small PNENs show indolent features. Consequently, selected cases can be considered for observation only, according to the National Comprehensive Cancer Network guideline, however, supporting clinical evidence is lacking. We investigated the clinical course of small PNENs and their risk factors for malignant potential. METHODS: A total of 158 patients with small pathologically confirmed PNENs ≤2 cm in initial imaging were retrospectively enrolled from 14 institutions. The primary outcome was any metastasis or recurrence event during follow-up. RESULTS: The median age was 57 years (range, 22-82 years), and 86 patients (54%) were female. The median tumor size at initial diagnosis was 13 mm (range, 7-20 mm). PNENs were pathologically confirmed by surgery in 137 patients and by EUS-guided fine needle aspiration biopsy (EUS-FNAB) in 21 patients. Eight patients underwent EUS-FNAB followed by surgical resection. The results of WHO grade were available in 150 patients, and revealed 123 grade 1, 25 grade 2, and 2 neuroendocrine carcinomas. A total of 145 patients (92%) underwent surgical resection, and three patients had regional lymph node metastasis. During the entire follow-up of median 45.6 months, 11 metastases or recurrences (7%) occurred. WHO grade 2 (HR 13.97, 95% CI 2.60-75.03, p = 0.002) was the only predictive factor for malignant potential in multivariable analysis. CONCLUSIONS: WHO grade is responsible for the malignant potential of small PNENs ≤2 cm. Thus, EUS-FNAB could be recommended in order to provide early treatment strategies of small PNENs.

Management of Small Pancreatic Neuroendocrine Neoplasm / 대한소화기암학회지

The incidence of small and asymptomatic pancreatic neuroendocrine neoplasms (PNENs) has been increased due to the widespread use of high-resolution imaging techniques and endoscopic procedures in screening programmes. Most of PNENs are indolent neoplasms with slow-growing. However, sometimes, PNENs show local invasion or metastasis with poor prognosis. The management of small, nonfunctioning PNENs remain under debate. The National Comprehensive Cancer Network guidelines recommend observation in selected cases of small PNENs less than 2 cm. Pancreatic surgeons are divided into two factions: “the hawks,” who indicate the high risk of malignancy even in small PNENs and, therefore, the need for an aggressive surgical treatment, and the “the doves,” who accepts the risk of malignancy in some ≤ 2 cm PNENs, advocate that the risk of overtreating many benign ≤ 2 cm PNENs would be much higher. As the pancreatic surgery remains a high-risk operation with a 28–30% morbidity and 1% mortality, the decision for small PNENs is challenging.

Management of Small Pancreatic Neuroendocrine Neoplasm / 대한소화기암학회지

The incidence of small and asymptomatic pancreatic neuroendocrine neoplasms (PNENs) has been increased due to the widespread use of high-resolution imaging techniques and endoscopic procedures in screening programmes. Most of PNENs are indolent neoplasms with slow-growing. However, sometimes, PNENs show local invasion or metastasis with poor prognosis. The management of small, nonfunctioning PNENs remain under debate. The National Comprehensive Cancer Network guidelines recommend observation in selected cases of small PNENs less than 2 cm. Pancreatic surgeons are divided into two factions: “the hawks,” who indicate the high risk of malignancy even in small PNENs and, therefore, the need for an aggressive surgical treatment, and the “the doves,” who accepts the risk of malignancy in some ≤ 2 cm PNENs, advocate that the risk of overtreating many benign ≤ 2 cm PNENs would be much higher. As the pancreatic surgery remains a high-risk operation with a 28–30% morbidity and 1% mortality, the decision for small PNENs is challenging.

Bakkenolides and Caffeoylquinic Acids from the Aerial Portion of Petasites japonicus and Their Bacterial Neuraminidase Inhibition Ability.

Petasites japonicus have been used since a long time in folk medicine to treat diseases including plague, pestilential fever, allergy, and inflammation in East Asia and European countries. Bioactive compounds that may prevent and treat infectious diseases are identified based on their ability to inhibit bacterial neuraminidase (NA). We aimed to isolate and identify bioactive compounds from leaves and stems of P. japonicas (PJA) and elucidate their mechanisms of NA inhibition. Key bioactive compounds of PJA responsible for NA inhibition were isolated using column chromatography, their chemical structures revealed using 1 H NMR, 13 C NMR, DEPT, and HMBC, and identified to be bakkenolide B (1), bakkenolide D (2), 1,5-di-O-caffeoylquinic acid (3), and 5-O-caffeoylquinic acid (4). Of these, 3 exhibited the most potent NA inhibitory activity (IC50 = 2.3 ± 0.4 µM). Enzyme kinetic studies revealed that 3 and 4 were competitive inhibitors, whereas 2 exhibited non-competitive inhibition. Furthermore, a molecular docking simulation revealed the binding affinity of these compounds to NA and their mechanism of inhibition. Negative-binding energies indicated high proximity of these compounds to the active site and allosteric sites of NA. Therefore, PJA has the potential to be further developed as an antibacterial agent for use against diseases associated with NA.

Effects of Branched-Chain Amino Acid (BCAA) Supplementation on the Progression of Advanced Liver Disease: A Korean Nationwide, Multicenter, Prospective, Observational, Cohort Study.

BACKGROUND AND AIMS: Clinical evidence for the benefits of branched-chain amino acids (BCAAs) is lacking in advanced liver disease. We evaluated the potential benefits of long-term oral BCAA supplementation in patients with advanced liver disease. METHODS: Liver cirrhosis patients with Child-Pugh (CP) scores from 8 to 10 were prospectively recruited from 13 medical centers. Patients supplemented with 12.45 g of daily BCAA granules over 6 months, and patients consuming a regular diet were assigned to the BCAA and control groups, respectively. The effects of BCAA supplementation were evaluated using the model for end-stage liver disease (MELD) score, CP score, serum albumin, serum bilirubin, incidence of cirrhosis-related events, and event-free survival for 24 months. RESULTS: A total of 124 patients was analyzed: 63 in the BCAA group and 61 in the control group. The MELD score (p = 0.009) and CP score (p = 0.011) significantly improved in the BCAA group compared to the control group over time. However, the levels of serum albumin and bilirubin in the BCAA group did not improve during the study period. The cumulative event-free survival was significantly improved in the BCAA group compared to the control group (HR = 0.389, 95% CI = 0.221-0.684, p < 0.001). CONCLUSION: Long-term supplementation with oral BCAAs can potentially improve liver function and reduce major complications of cirrhosis in patients with advanced liver disease.

The Research Trends of Pharmacopuncture Therapy on Cervical Pain Caused by Traffic Accidents.

OBJECTIVES: The purpose of this study is to comprehensively review Korean domestic studies and investigate the research trends of pharmacopuncture therapy on cervical pain caused by traffic accidents. METHODS: Domestic studies between February 1999 and May 2020 from four Korean databases were searched with combinations of keywords 'cervical pain', 'traffic accident', 'whiplash injury', and 'pharmacopuncture'. RESULTS: 17 studies were selected for review, including 7 randomized controlled trials, 5 retrospective observational studies, 3 case reports, and 2 non-randomized controlled trials. Each study was reviewed by published year, study type, types of pharmacopuncture solutions, selected acupuncture points, dosage of pharmacopuncture solutions, frequency of treatment, concurrent treatments, outcome measurements, and the effectiveness of pharmacopuncture therapy. The results are as follows (1) It showed that the total number of published studies had increased slightly in the last 10 years compared to the previous decade. (2) The pharmacopuncture solutions used in the studies were in the following order Bee-Venom (), Jungsongouhyul (), Hwangryunhaedoktang () and Soyeom (). Frequently used acupuncture points were GB20, GV21, A-shi point, GV16, EX-B2, and SI15 in order. (3) The most commonly used total injection dosage was 1.0 cc at a time, and the frequency of treatment was twice a week. (4) Concurrent treatments such as acupuncture, herbal medication, physical therapy and Chuna manual therapy were performed in all 17 studies. (5) Pharmacopuncture therapy showed positive effects on cervical pain caused by traffic accidents in all 17 studies reviewed. CONCLUSION: Pharmacopuncture therapy was effective in cervical pain caused by traffic accidents in all 17 studies selected. Further studies will be needed using more larger scales and more objective data to confirm the effectiveness of pharmacopuncture therapy and to generalize its application.

Constituents of the leaves and twigs of Elaeagnus umbellata and their proliferative effects on human keratinocyte HaCaT cells.

Bioassay-guided fractionation of an extract of leaves and twigs of Elaeagnus umbellata led to the isolation of a serotonin derivative, N-[2-(5-hydroxyl-1H-indol-3-yl)ethyl]-butanamide (1), along with six flavonoid glycosides, kaempferol-3-O-ß-d-xylopyranosyl(1 → 2)-ß-d-galactopyranoside-7-O-α-l-rhamnopyranoside (2), kaempferol-3-O-ß-d-galactopyranoside-7-O-α-l-rhamnopyranoside (3), kaempferol-3-O-α-l-rhamnopyranosyl(1 → 6)-ß-d-galactopyranoside-7-O-α-l-rhamnopyranoside (4), kaempferol-3-O-ß-d-xylopyranosyl(1 → 2)-ß-d-galactopyranoside (5), kaempferol-3-O-rutinoside (6), and kaempferol-3-O-ß-d-glucopyranosyl(1 → 2)-ß-d-galactopyranoside-7-O-α-l-rhamnopyranoside (7). Their structures were elucidated using 1D/2D nuclear magnetic resonance spectroscopy and mass spectrometry. Compounds 1-6 were evaluated for their proliferative effects on HaCaT keratinocytes; 1-5 promoted keratinocyte proliferation dose dependently. Compounds 3 and 4 showed potent activities. These results suggest that the leaves and twigs of E. umbellata have wound healing and skin cell regeneration potentials.

Changes in the neutrophil-to-lymphocyte ratio predict the prognosis of patients with advanced hepatocellular carcinoma treated with sorafenib.

BACKGROUND AND AIM: Although sorafenib is the first systemic therapy to show survival benefit for advanced hepatocellular carcinoma (HCC), its survival benefit is variable for HCC. Systemic inflammation may be associated with survival in HCC. We investigated the use of systemic inflammation markers, including neutrophil-to-lymphocyte ratio (NLR), in the prognosis of sorafenib-treated HCC patients. PATIENTS AND METHODS: We retrospectively analyzed data of 82 patients with advanced HCC who received sorafenib as the first-line treatment. Data on pretreatment and post-treatment (2-3 months after initiating sorafenib therapy, first tumor response evaluation day) clinical, laboratory, and tumor characteristics were collected. Survival-related prognostic factors were analyzed. RESULTS: Patients were mostly in the intermediate (12.2%) or advanced (87.8%) Barcelona Clinic Liver Cancer stages. Fifty-six (68.3%) patients had vascular invasion and 34 (41.5%) patients had extrahepatic disease. The median progression-free survival (PFS) and overall survival (OS) were 4.7 months [95% confidence interval (CI): 2.8-6.5 months] and 4.7 months (95% CI: 2.8-6.5 months). In multivariate analysis for OS, diarrhea (hazard ratio: 0.588; 95% CI: 0.348-0.993) and NLR decline (decreased compared with pretreatment) (hazard ratio: 0.479; 95% CI: 0.300-0.765) were independent factors of good OS. In the NLR decline group, the median PFS and OS were 7.1 and 7.3 months, respectively. In the NLR nondecline group, the median PFS and OS were 3.0 and 3.2 months, respectively. The difference in OS between the two groups was significant (P = 0.004). CONCLUSION: A change in NLR after sorafenib therapy was associated with a better prognosis in patients with advanced HCC.

Synthetic lethal interaction between oxidative stress response and DNA damage repair in the budding yeast and its application to targeted anticancer therapy.

Synthetic lethality is an extreme form of negative genetic epistasis that arises when a combination of functional deficiency in two or more genes results in cell death, whereas none of the single genetic perturbations are lethal by themselves. This unconventional genetic interaction is a modification of the concept of essentiality that can be exploited for the purpose of targeted cancer therapy. The yeast Saccharomyces cerevisiae has been pivotally used for early large-scale synthetic lethal screens due to its experimental advantages, but recent advances in gene silencing technology have now made direct high-throughput analysis possible in higher organisms. Identification of tumor-specific alterations and characterization of the mechanistic principles underlying synthetic lethal interaction are the key to applying synthetic lethality to clinical cancer treatment by enabling genome-driven oncological research. Here, we provide emerging ideas on the synthetic lethal interactions in budding yeast, particularly between cellular processes responsible for oxidative stress response and DNA damage repair, and discuss how they can be appropriately utilized for context-dependent cancer therapeutics.

Changes in the regional shape and volume of subcortical nuclei in patients with tinnitus comorbid with mild hearing loss.

PURPOSE: Tinnitus, the perception of sound without an external source, is a prevalent disease, but its underlying mechanism has not been fully elucidated. Recent studies have suggested the involvement of subcortical nuclei in tinnitus generation. We investigated changes in the local shape and volume of subcortical nuclei in relation to tinnitus. METHODS: The participants included 53 patients with tinnitus and 52 age- and gender-matched normal controls. Individual 3D T1-weighted structural images were obtained using 3-T magnetic resonance imaging. Surface-based vertex analysis (SVA) was performed with automated segmentation of the bilateral caudate nuclei, putamina, nucleus accumbens, thalami, pallidum, hippocampi, amygdalae, and brainstem. The scalar distances from the mean surface and volumes of 15 nuclei were compared between the tinnitus and control groups and correlated with tinnitus handicap score (THI) and tinnitus duration. RESULTS: SVA revealed regional contractions in the accessory basal and lateral nuclei of the right amygdala and expansions in the left medial and right ventral posterior nuclei and lateral dorsal nucleus of both thalami. The surface distances of the right nucleus accumbens were positively correlated with tinnitus duration, while those of the left nucleus accumbens and left hippocampus were negatively correlated with THI. CONCLUSION: Regional atrophy of the amygdala may indicate self-modulation of emotional response regulation to diminish tinnitus-related emotional distress. Thalamic regional expansion may signify dysfunctional auditory gating in the thalamus, where inhibition of the tinnitus signal at the thalamus level is disrupted due to abnormal changes in the limbic system, ultimately leading to the tinnitus percept.

Regulatory Effects of Black Rice Extract on Helicobacter pylori Infection-Induced Apoptosis.

SCOPE: Black rice extract (BRE) contains cyanidin 3-O-glucoside (C3G), an anthocyanin, as the major component. In this study, we found that BRE inhibits the mRNA and protein expression of genes encoding cytotoxin-associated protein A (cagA) and vacuolating protein A (vacA) in Helicobacter pylori 60190 strain. METHODS AND RESULTS: We performed RT-PCR and western blotting to show that BRE inhibits the mRNA and protein expression of SecA. Because SecA is involved in VacA export in bacteria, our result suggests a positive correlation between BRE-induced inhibition of secA expression and VacA secretion. Further, we perform MTT assay and flow cytometry to show that BRE decreases the apoptosis of H. pylori-infected KATO III cells. Finally, we perform western blotting to show that the cell-protective effect of BRE is associated with decreased levels of active proapoptotic proteins caspases and PARP and increased levels of antiapoptotic proteins survivin and XIAP in H. pylori-infected cells. CONCLUSION: Thus, our results indicate that BRE acts as a potent inhibitor of the biogenesis of H. pylori virulence proteins and decreases the apoptosis of H. pylori-infected cells. Moreover, our results suggest that BRE can be used to exert beneficial effects in patients with gastroduodenal diseases caused by H. pylori.