Microbiome signatures associated with clinical stages of gastric Cancer: whole metagenome shotgun sequencing study.

BACKGROUND: Gastric cancer is one of the global health concerns. A series of studies on the stomach have confirmed the role of the microbiome in shaping gastrointestinal diseases. Delineation of microbiome signatures to distinguish chronic gastritis from gastric cancer will provide a non-invasive preventative and treatment strategy. In this study, we performed whole metagenome shotgun sequencing of fecal samples to enhance the detection of rare bacterial species and increase genome sequence coverage. Additionally, we employed multiple bioinformatics approaches to investigate the potential targets of the microbiome as an indicator of differentiating gastric cancer from chronic gastritis. RESULTS: A total of 65 patients were enrolled, comprising 33 individuals with chronic gastritis and 32 with gastric cancer. Within each group, the chronic gastritis group was sub-grouped into intestinal metaplasia (n = 15) and non-intestinal metaplasia (n = 18); the gastric cancer group, early stage (stages 1 and 2, n = 13) and late stage (stages 3 and 4, n = 19) cancer. No significant differences in alpha and beta diversities were detected among the patient groups. However, in a two-group univariate comparison, higher Fusobacteria abundance was identified in phylum; Fusobacteria presented higher abundance in gastric cancer (LDA scored 4.27, q = 0.041 in LEfSe). Age and sex-adjusted MaAsLin and Random Forest variable of importance (VIMP) analysis in species provided meaningful features; Bacteria_caccae was the most contributing species toward gastric cancer and late-stage cancer (beta:2.43, se:0.891, p:0.008, VIMP score:2.543). In contrast, Bifidobacterium_longum significantly contributed to chronic gastritis (beta:-1.8, se:0.699, p:0.009, VIMP score:1.988). Age, sex, and BMI-adjusted MasAsLin on metabolic pathway analysis showed that GLCMANNANAUT-PWY degradation was higher in gastric cancer and one of the contributing species was Fusobacterium_varium. CONCLUSION: Microbiomes belonging to the pathogenic phylum Fusobacteria and species Bacteroides_caccae and Streptococcus_anginosus can be significant targets for monitoring the progression of gastric cancer. Whereas Bifidobacterium_longum and Lachnospiraceae_bacterium_5_1_63FAA might be protection biomarkers against gastric cancer.

Protective effects of statins on the incidence of NAFLD-related decompensated cirrhosis in T2DM.

BACKGROUND AND AIMS: Non-alcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome and poses a significant threat to patients with type 2 diabetes mellitus (T2DM) and metabolic dysregulation. Statins exert anti-inflammatory, antioxidative and antithrombotic effects that target mechanisms underlying NAFLD. However, the protective effects of the different doses, intensities and types of statins on the incidence of NAFLD-related decompensated liver cirrhosis (DLC) in patients with T2DM remain unclear. METHODS: This study used the data of patients with T2DM who were non-HBV and non-HCV carriers from a national population database to examine the protective effects of statin use on DLC incidence through propensity score matching. The incidence rate (IR) and incidence rate ratios (IRRs) of DLC in patients with T2DM with or without statin use were calculated. RESULTS: A higher cumulative dose and specific types of statins, namely rosuvastatin, pravastatin, atorvastatin, simvastatin and fluvastatin, reduced the risk of DLC in patients with T2DM. Statin use was associated with a significant reduction in the risk of DLC (HR: .65, 95% CI: .61-.70). The optimal daily intensity of statin use with the lowest risk of DLC was .88 defined daily dose (DDD). CONCLUSIONS: The results revealed the protective effects of specific types of statins on DLC risk in patients with T2DM and indicated a dose-response relationship. Additional studies are warranted to understand the specific mechanisms of action of different types of statins and their effect on DLC risk in patients with T2DM.

Fucoidan and Fucoxanthin Attenuate Hepatic Steatosis and Inflammation of NAFLD through Modulation of Leptin/Adiponectin Axis.

Non-alcoholic fatty liver disease (NAFLD) is the emerging cause of chronic liver disease globally and lack of approved therapies. Here, we investigated the feasibility of combinatorial effects of low molecular weight fucoidan and high stability fucoxanthin (LMF-HSFx) as a therapeutic approach against NAFLD. We evaluated the inhibitory effects of LMF-HSFx or placebo in 42 NAFLD patients for 24 weeks and related mechanism in high fat diet (HFD) mice model and HepaRGTM cell line. We found that LMF-HSFx reduces the relative values of alanine aminotransferase, aspartate aminotransferase, total cholesterol, triglyceride, fasting blood glucose and hemoglobin A1c in NAFLD patients. For lipid metabolism, LMF-HSFx reduces the scores of controlled attenuation parameter (CAP) and increases adiponectin and leptin expression. Interestingly, it reduces liver fibrosis in NAFLD patients, either. The proinflammatory cytokines interleukin (IL)-6 and interferon-γ are reduced in LMF-HSFx group. In HFD mice, LMF-HSFx attenuates hepatic lipotoxicity and modulates adipogenesis. Additionally, LMF-HSFx modulates SIRI-PGC-1 pathway in HepaRG cells under palmitic acid-induced lipotoxicity environment. Here, we describe that LMF-HSFx ameliorated hepatic steatosis, inflammation, fibrosis and insulin resistance in NAFLD patients. LMF-HSFx may modulate leptin-adiponectin axis in adipocytes and hepatocytes, then regulate lipid and glycogen metabolism, decrease insulin resistance and is against NAFLD.

Comparison of the Phytochemical Properties, Antioxidant Activity and Cytotoxic Effect on HepG2 Cells in Mongolian and Taiwanese Rhubarb Species.

The Mongolian rhubarb-Rheum undulatum L. (RU)-and Rumex crispus L. (RC)-a Taiwanese local rhubarb belonging to the family of Polygonaceae-are principal therapeutic materials in integrative medicine due to their rich quantities of bioactive compounds; however, their phytochemical and antioxidant properties, and anti-cancer activity is poorly investigated. Furthermore, the phytochemical characteristics of both species may be affected by their different geographical distribution and climatic variance. The current study aimed to compare RU with RC extracts in different polarity solvents (n-hexane, ethyl acetate, acetone, ethanol, and water) for their phytochemical contents including the total phenolic content (TPC), total anthraquinone content (TAC), total flavonoid content (TFC), antioxidant and free radical scavenging capacities, and anticancer ability on the HepG2 cell. Except for the n-hexane extract, all of the RU extracts had considerably higher TPCs than RC extracts, ranging from 8.39 to 11.16 mg gallic acid equivalent (GAE) per gram of dry weight, and the TPCs of each extract were also significantly correlated with their antioxidant capacities by ABTS, DPPH, and FRAP assays (p < 0.05). Moreover, there was no remarkable association between the antioxidant capacities and either TACs or TFCs in both the RU and RC extracts. Besides, high-performance liquid chromatography (HPLC) analysis revealed that both the RU and RC extracts contained chrysophanol, emodin, and physcion, and those bioactive compounds were relatively higher in the n-hexane solvent extracts. Additionally, we observed different levels of dose-dependent cytotoxic effects in all the extracts by cell viability assay. Notably, the ethanol extract of RU had a compelling cytotoxic effect with the lowest half-maximum inhibition concentration (IC50-171.94 ± 6.56 µg/mL at 48 h) among the RU extracts than the ethanol extract of RC. Interestingly, the ethanol extract of RU but not RC significantly induced apoptosis in the human liver cancer cell line, HepG2, with a distinct pattern in caspase-3 activation, resulting in increased PARP cleavage and DNA damage. In summary, Mongolian Rhubarb, RU, showed more phytochemical contents, as well as a higher antioxidant capacity and apoptotic effect to HepG2 than RC; thus, it can be exploited for the proper source of natural antioxidants and liver cancer treatment in further investigation.

A meta-analysis of students' readiness assurance test performance with team-based learning.

BACKGROUND: Team-based learning (TBL) is increasingly being utilized across medical fields by engaging students in small group discussions. The readiness assurance test (RAT) is an essential feature that differentiates TBL from problem-based learning (PBL) activity sequences. No publication has discussed differences in the RAT in TBL in medical schools. The purpose of this meta-analysis study was to examine the performance of learners in terms of group RAT (GRAT) and individual RAT (IRAT) scores in TBL for students of healthcare professions. METHODS: Databases, including PubMed and Cochrane were searched using several terms. We assessed the quality of included studies and conducted a meta-analysis. RESULTS: In total, 11 studies with 1575 participants were identified. Quality assessment scores of these studies ranged 4 ~ 7. Mean GRAT scores were significantly higher than mean IRAT scores (standardized mean difference (SMD) = 2.027, 95% confidence interval (CI) = 1.657 ~ 2.486, p heterogeneity < 0.001). Although the test of subgroup differences was insignificant (p = 0.113), the nursing-only subgroup showed much better performance in the GRAT than the IRAT (SMD = 2.3CI: 95% CI = 2.0 ~ 2.6, I2 = 48.77%) compared to the others subgroup which included students from different majors. The subgroup analysis explained the heterogeneity in the overall analysis. Because of inadequate information from these 11 studies, a meta-regression could not explore the source of heterogeneity in terms of the mean age, duration of the intervention, preparation time before the RAT, and previous TBL experienced by students. CONCLUSIONS: Students achieved significantly higher scores for the GRAT than for the IRAT, especially the group which only included nursing students, which implies excellent collaboration in the group of nursing students.

Taiwanese consensus recommendations for acute pancreatitis.

The incidence of acute pancreatitis and related health care utilization are increasing. Acute pancreatitis may result in organ failure and various local complications with risks of morbidity and even mortality. Recent advances in research have provided novel insights into the assessment and management for acute pancreatitis. This consensus is developed by Taiwan Pancreas Society to provide an updated, evidence-based framework for managing acute pancreatitis.

Pro-apoptotic effect of haem oxygenase-1 in human colorectal carcinoma cells via endoplasmic reticular stress.

Several biological effects of haem oxygenase (HO)-1, including anti-inflammatory, antiapoptotic and antioxidative properties were reported; however, the role of HO-1 in apoptosis is still unclear. In the presence of stimulation by cobalt protoporphyrin (CoPP), an HO-1 inducer, apoptotic characteristics were observed, including DNA laddering, hypodiploid cells, and cleavages of caspase (Casp)-3 and poly(ADP) ribose polymerase (PARP) proteins in human colon carcinoma COLO205, HCT-15, LOVO and HT-29 cells in serum-free (SF) conditions with increased HO-1, but not heat shock protein 70 (HSP70) or HSP90. The addition of 10% foetal bovine serum (FBS) or 1% bovine serum albumin accordingly inhibited CoPP-induced apoptosis and HO-1 protein expression in human colon cancer cells. CoPP-induced apoptosis of colon cancer cells was prevented by the addition of the pan-caspase inhibitor, Z-VAD-FMK (VAD), and the Casp-3 inhibitor, Z-DEVD-FMK (DEVD). N-Acetyl cysteine inhibited reactive oxygen species-generated H2 O2 -induced cell death with reduced intracellular peroxide production, but did not affect CoPP-induced apoptosis in human colorectal carcinoma (CRC) cells. Two CoPP analogs, ferric protoporphyrin and tin protoporphyrin, did not affect the viability of human CRC cells or HO-1 expression by those cells, and knockdown of HO-1 protein expression by HO-1 small interfering (si)RNA reversed the cytotoxic effect elicited by CoPP. Furthermore, the carbon monoxide (CO) donor, CORM, but not FeSO4 or biliverdin, induced DNA ladders, and cleavage of Casp-3 and PARP proteins in human CRC cells. Increased phosphorylated levels of the endoplasmic reticular (ER) stress proteins, protein kinase R-like ER kinase (PERK), and eukaryotic initiation factor 2α (eIF2α) by CORM and CoPP were identified, and the addition of the PERK inhibitor, GSK2606414, inhibited CORM- and CoPP-induced apoptosis. Increased GRP78 level and formation of the HO-1/GRP78 complex were detected in CORM- and CoPP-treated human CRC cells. A pro-apoptotic role of HO-1 against the viability of human CRC cells via induction of CO and ER stress was firstly demonstrated herein.

Correlation between early clinical exposure environment, attitudes toward basic medicine, and medical students' basic science learning performance.

BACKGROUND: Early clinical exposure (ECE) is viewed as a way to provide contexts of basic science and highlight its relevance to medical practice. However, very few studies have specifically looked into how the ECE experience contributes to students' academic performance. The purpose of this study was to investigate whether ECE experiences (external cause) or students' learning attitudes (internal cause) more closely correlated with medical students' academic performance. METHODS: Subjects who participated in the study comprised 109 s-year students at Taipei Medical University. Fifty of the 109 study participants were enrolled in an elective ECE program. The dependent variable in this study was the test score of a systems-based basic sciences (SBBS) course. Independent variables of the study included students' attitudes and test anxiety towards the SBBS course, engagement/length of time spent in ECE, and the ECE learning environment. Data of students' engagement in ECE, levels of their motivational beliefs and test anxiety, differences in the ECE learning environment, and the SBBS final test scores of these 109 respondents were collected for hierarchical multiple regression (HMR) analyses. RESULTS: Results of the HMR analyses revealed that students' test anxiety towards basic science and also the learning environment of the ECE had significant positive predictive power on their SBBS test scores. CONCULSION: This study discovers that medical students' academic performance in basic science correlates not only with their anxiety to testing, but even more so with the clinical environment they are exposed to. Hence we suggest including further investigations about different learning environments on ECE experiences in future studies.

Inhibitory Effects of Scutellaria baicalensis Root Extract on Linoleic Acid Hydroperoxide-induced Lung Mitochondrial Lipid Peroxidation and Antioxidant Activities.

In this study, we evaluated the ability of Scutellaria baicalensis Georgi to protect lipid-peroxidation (LPO) in lung tissue after free radical-induced injury. We prepared S. baicalensis root (SBR) extracts using different solvents. The total flavonoid and total phenol contents of each extract were measured, and the ROS damage protection was evaluated by analyzing linoleic acid hydroperoxide (LHP)-induced LPO in rat lung mitochondria. Moreover, evaluating diphenylpicrylhydrazyl (DPPH), hydrogen peroxide, superoxide anion radical, and hydroxyl radical scavenging abilities and using metal chelating assays were used to determine in vitro antioxidant activity. The ethyl acetate (EtOAc) extract showed high ROS scavenging ability, and four compounds were subsequently isolated and purified from this extract: baicalin, baicalein, wogonin, and oroxylin A. Baicalein in rat lung mitochondria the most significant LHP-induced LPO inhibition was shown and extracted with EtOAc that contained the highest amount of baicalein. Thus, baicalein and the EtOAc extract of SBR may be efficient in conferring ROS damage protection and inhibiting LHP-induced LPO in rat lung mitochondria. Additional studies are warranted to investigate their use as antioxidant therapy for respiration infections, nutrition supplements, and lead compounds in pharmaceuticals.

Anti-Inflammatory and Anticancer Properties of Bioactive Compounds from Sesamum indicum L.-A Review.

The use of foodstuff as natural medicines has already been established through studies demonstrating the pharmacological activities that they exhibit. Knowing the nutritional and pharmacological significance of foods enables the understanding of their role against several diseases. Among the foods that can potentially be considered as medicine, is sesame or Sesamum indicum L., which is part of the Pedaliaceae family and is composed of its lignans such as sesamin, sesamol, sesaminol and sesamolin. Its lignans have been widely studied and are known to possess antiaging, anticancer, antidiabetes, anti-inflammatory and antioxidant properties. Modern chronic diseases, which can transform into clinical diseases, are potential targets of these lignans. The prime example of chronic diseases is rheumatic inflammatory diseases, which affect the support structures and the organs of the body and can also develop into malignancies. In line with this, studies emphasizing the anti-inflammatory and anticancer activities of sesame have been discussed in this review.

Feasibility and safety of a novel magnetic-assisted capsule endoscope system in a preliminary examination for upper gastrointestinal tract.

BACKGROUND AND STUDY AIM: Current capsule endoscopy procedures are ineffective for upper gastrointestinal (GI) tract examination because they do not allow for operator-controlled navigation of the capsule. External controllability of a capsule endoscope with an applied magnetic field is a possible solution to this problem. We developed a novel magnetic-assisted capsule endoscope (MACE) system to visualize the entire upper GI tract. The present study evaluated the safety and feasibility of the MACE system for the examination of the upper GI tract, including the esophagus, stomach, and duodenum. METHODS: The present open clinical study enrolled ten healthy volunteers. All participants swallowed a MACE, and an external magnetic field navigator was used for magnetic capsule manipulation in the upper GI tract. We assessed the maneuverability of the magnetic capsule and completeness of the MACE examination as well as the safety and tolerability of the procedure. RESULTS: The present study enrolled ten healthy volunteers with a mean age and body mass index of 47.7 years and 25.6 kg/m2, respectively. One volunteer withdrew because of difficulty in swallowing the capsule. In total, nine volunteers underwent the MACE examination. The average examination time was 27.1 min. The maneuverability of the capsule was assessed as good and fair in 55.6 and 44.4% of the participants, respectively. The overall completeness of the examination in the esophagus, stomach, and duodenum was 100, 85.2, and 86.1%, respectively. No severe adverse events occurred during this study. All participants exhibited satisfactory tolerance of the MACE examination. CONCLUSION: The MACE system has satisfactory maneuverability and visualization completeness with excellent acceptance and tolerance.

Reactive oxygen species-dependent nitric oxide production in reciprocal interactions of glioma and microglial cells.

Conditioned mediums (CMs) from glioma cells U87, GBM-8401, and C6 significantly induced iNOS protein and NO production by microglial cells BV-2 but without altering the cell viability or cell-cycle progression of BV2 microglia. Significant increases in intracellular peroxide by U87-CM and C6-CM were detected by a DCHF-DA assay, and vitamin (Vit) C and N-acetyl cysteine (NAC)-reduced intracellular peroxide levels elicited by CMs lead to inhibition of iNOS/NO production The extracellular signal-regulated kinase (ERK) inhibitor, U0126, and c-Jun N-terminal kinase (JNK) inhibitor, SP600125, suppressed U87-CM- and C6-CM-induced iNOS/NO production by respectively blocking phosphorylated ERK (pERK) and JNK (pJNK) protein expressions stimulated by U87-CM and C6-CM. Increased migration of U87 and C6 glioma cells by a co-culture with BV-2 microglial cells or adding the nitric oxide (NO) donor, sodium nitroprusside (SNP) was observed, and that was blocked by adding an NO synthase (NOS) inhibitor, N-nitro L-arginine methyl ester (NAME). Contributions of ROS, pERK, and pJNK to the migration of glioma cells was further demonstrated in a transwell coculture system of U87 and C6 gliomas with BV-2 microglial cells. Furthermore, expressions of tumor necrosis factor (TNF)-α and monocyte chemoattractant protein (MCP)-1 messenger (m)RNA in U87 and C6 cells were detected by an RT-PCR, and TNF-α and MCP-1 induced iNOS protein expression in time- and concentration-dependent manners. Neutralization of TNF-α or MCP-1 in U87-CM and C6-CM using a TNF-α or MCP-1 antibody inhibited iNOS protein expression, and increased intracellular peroxide by TNF-α or MCP-1 was identified in BV-2 cells. The reciprocal activation of glioma cells and microglia via ROS-dependent iNOS/NO elevation at least partially mediated by TNF-α and MCP-1 is elucidated.

N-acetyl-L-cysteine enhances fisetin-induced cytotoxicity via induction of ROS-independent apoptosis in human colonic cancer cells.

Oxidative stress or excessive antioxidant levels-caused redox imbalance can alter apoptotic responses, and N-acetyl-L-cysteine (NAC) was able to inhibit H2 O2 -mediated cell death, but unable to prevent apoptosis induced by other chemicals such as etoposide. We now demonstrate that 10 and 20 mM NAC, non-toxic concentrations, can enhance fisetin (FIS)-mediated apoptosis in colon cancer cells COLO205. Compared to treatment with FIS alone, combination treatment with NAC increased the expression of cleaved caspase-3 and PAPR protein, and produced greater density of DNA ladders. NAC reduced the mitochondrial membrane potential of FIS-treated COLO205 cells with induction of caspase 9 protein cleavage. DNA ladders induced by FIS + NAC were diminished by adding the caspase 3 inhibitor, DEVD-FMK, and the caspase 9 inhibitor, YVAD-FMK. Combinatorial treatment COLO205 cells with NAC and FIS showed potent inhibition on ERK protein phosphorylation, compared with those from FIS or NAC-treated groups by Western blotting using specific antibodies. Addition of the chemical ERK inhibitors, PD98059 and U0126, significantly inhibited ERK protein phosphorylation, accompanied by induced DNA ladder formation, cleavage of caspase 3 and PARP protein in COLO205 cells. Furthermore, NAC showed an enhancement on a FIS-related chemical chrysin-induced apoptosis of COLO205 cells, and NAC sensitization of colon cancer cells to FIS-induced apoptosis was also identify in colonic cancer cells HCT-116, HT-29, and HCT-15 cells. The evidence to support NAC sensitizing human colon cancer cells to FIS-induced apoptosis was provided, and application of NAC and FIS as a strategy to treat colonic cancer deserved for further in vivo study.

Relationship between hemoglobin levels and risk for suspected non-alcoholic fatty liver in Taiwanese adults.

Body iron levels have recently been shown to be a strong predictor for non-alcoholic fatty liver disease (NAFLD). The aims of this study were to investigate the prevalence of NAFLD in a general adult population, and to investigate the relationship between body iron levels, NAFLD and the metabolic syndrome (MetS). 2186 adults participated in the third National Nutrition and Health Survey in Taiwan (NAHSIT, 2005-2008). The participants underwent anthropometry measurements and phlebotomy after an overnight fast, and those with excessive alcohol intake, iron overload of serum ferritin > 600 ng/ml, hepatitis viral infection and hepatocellular carcinoma were excluded. Suspected NAFLD was diagnosed by three alanine transaminase (ALT) cut-points: cut-point 1: serum ALT > 40 U/l; cut-point 2: ALT ≥ 25 U/l for male and ALT ≥ 17 U/l for female; and cut-point 3: ALT ≥ 35 U/l for male and ALT ≥ 26 U/l for female. The prevalence proportion of suspected NAFLD among Taiwanese adults was 6.6% (cut-point 1), 36% (cut-point 2); and 14.3% (cut-point 3). Body iron levels were significantly higher in individuals with suspected NAFLD compared with those without. Distribution of hemoglobin levels, but not serum ferritin levels, by decade of age showed strong correlation with the prevalence of suspected NAFLD in individuals with MetS. Multivariate adjusted odds ratio (OR) showed that the best predictors for suspected NAFLD with the MetS were hemoglobin [OR 1.43 (1.21-1.68); P < 0.0001] and hyperlipidemia [OR 1.52 (1.19-1.94); P = 0.0007]. In individuals without MetS, the adjusted OR of suspected NAFLD was markedly higher for hemoglobin [OR 1.25 (1.12-1.41); P < 0.0001]. In conclusion, adults with high hemoglobin levels (14.4 µg/dl for male and 13.2 µg/dl for female) are at the greatest risk for developing abnormal liver function. Hemoglobin test should be considered as a part of clinical evaluation for patients with NAFLD.

Bacteriophage-cocktail hydrogel dressing to prevent multiple bacterial infections and heal diabetic ulcers in mice.

Bacteriophage (phage) has been reported to reduce the bacterial infection in delayed-healing wounds and, as a result, aiding in the healing of said wounds. In this study we investigated whether the presence of phage itself could help repair delayed-healing wounds in diabetic mice. Three strains of phage that target Salmonella enterica, Escherichia coli, and Pseudomonas aeruginosa were used. To prevent the phage liquid from running off the wound, the mixture of phage (phage-cocktail) was encapsulated in a porous hydrogel dressing made with three-dimensional printing. The phage-cocktail dressing was tested for its phage preservation and release efficacy, bacterial reduction, cytotoxicity with 3T3 fibroblast, and performance in repairing a sterile full-thickness skin wound in diabetic mice. The phage-cocktail dressing released 1.7%-5.7% of the phages embedded in 24 h, and reduced between 37%-79% of the surface bacteria compared with the blank dressing (p <.05). The phage-cocktail dressing exhibited no sign of cytotoxicity after 3 days (p <.05). In vivo studies showed that 14 days after incision, the full-thickness wound treated with a phage-cocktail dressing had a higher wound healing ratio compared with the blank dressing and control (p <.01). Histological analysis showed that the structure of the skin layers in the group treated with phage-cocktail dressing was restored in an orderly fashion. Compared with the blank dressing and control, the repaired tissue in the phage-cocktail dressing group had new capillary vessels and no sign of inflammation in its dermis, and its epidermis had a higher degree of re-epithelialization (p <.05). The slow-released phage has demonstrated positive effects in repairing diabetic skin wounds.

Fatigue and physical activity levels in patients with liver cirrhosis.

AIMS AND OBJECTIVES: This study aimed to explore the correlation between fatigue and physical activity in patients with liver cirrhosis. BACKGROUND: Many patients with liver cirrhosis perceive lower physical functioning and more fatigue than non-cirrhotic individuals. To date, however, few studies have examined the relationship between fatigue and physical activity in this patient population. DESIGN: This study used a correlation design. Participants were patients with liver cirrhosis recruited from the gastroenterology clinic of a teaching medical centre in Taiwan. METHODS: Data were collected using a structured questionnaire, consisting of a fatigue scale and a seven-day Physical Activity Recall scale. spss version 13.0 software was used to analyse the data through statistical methods, including one-way analysis of variance, independent t-test and Pearson's correlations. RESULTS: Patients participating in this study suffered from moderate-to-severe fatigue, and their engagement in physical activity of moderate or higher intensity was decreased. On average, fatigue had a moderate level of influence on physical activity. A significant negative correlation was found between the fatigue level and average seven-day physical activity level. CONCLUSIONS: Patients with liver cirrhosis can experience severe fatigue, which may reduce their level of physical activity. RELEVANCE TO CLINICAL PRACTICE: Early evaluation of the fatigue level and physical activity constraints in patients with liver cirrhosis should be conducted in the clinic or community. Individualised instructions for patient's physical activity should be provided.

Arthrospira Enhances Seroclearance in Patients with Chronic Hepatitis B Receiving Nucleos(t)ide Analogue through Modulation of TNF-α/IFN-γ Profile.

Chronic hepatitis B (CHB) virus infection, causing immune dysfunction and chronic hepatitis, is one of the leading risk factors for hepatocellular cancer. We investigated how Arthrospira affected hepatitis B surface antigen (HBsAg) reduction in CHB patients under continued nucleos(t)ide analogues (NA). Sixty CHB patients who had been receiving NA for at least one year with undetectable HBV DNA were randomized into three groups: control and oral Arthrospira at 3 or 6 g daily add-on therapy groups. Patients were followed up for 6 months. Oral Arthrospira-diet mice were established to investigate the possible immunological mechanism of Arthrospira against HBV. Within 6 months, mean quantitative HBsAg (qHBsAg) decreased in the oral Arthrospira add-on therapy group. Interestingly, interferon gamma (IFN-γ) increased but TNF-α, interleukin 6 (IL-6), hepatic fibrosis, and steatosis decreased in the add-on groups. In mice, Arthrospira enhanced both innate and adaptive immune system, especially natural killer (NK) cell cytotoxicity, B cell activation, and the interleukin 2 (IL-2), IFN-γ immune response. Arthrospira may modulate IL-2- and TNF-α/IFN-γ-mediated B and T cell activation to reduce HBsAg. Also, Arthrospira has the potential to restore immune tolerance and enhance HBsAg seroclearance in CHB patients through promoting T, B, and NK cell activation.

Exploring Gut Microenvironment in Colorectal Patient with Dual-Omics Platform: A Comparison with Adenomatous Polyp or Occult Blood.

The gut mucosa is actively absorptive and functions as the physical barrier to separate the gut ecosystem from host. Gut microbiota-utilized or food-derived metabolites are closely relevant to the homeostasis of the gut epithelial cells. Recent studies widely suggested the carcinogenic impact of gut dysbiosis or altered metabolites on the development of colorectal cancer (CRC). In this study, liquid chromatography coupled-mass spectrometry and long-read sequencing was applied to identify gut metabolites and microbiomes with statistically discriminative abundance in CRC patients (n = 20) as compared to those of a healthy group (n = 60) ofenrolled participants diagnosed with adenomatous polyp (n = 67) or occult blood (n = 40). In total, alteration in the relative abundance of 90 operational taxonomic units (OTUs) and 45 metabolites were identified between recruited CRC patients and healthy participants. Among the candidates, the gradual increases in nine OTUs or eight metabolites were identified in healthy participants, patients diagnosed with occult blood and adenomatous polyp, and CRC patients. The random forest regression model constructed with five OTUs or four metabolites achieved a distinct classification potential to differentially discriminate the presence of CRC (area under the ROC curve (AUC) = 0.998 or 0.975) from the diagnosis of adenomatous polyp (AUC = 0.831 or 0.777), respectively. These results provide the validity of CRC-associated markers, including microbial communities and metabolomic profiles across healthy and related populations toward the early screening or diagnosis of CRC.

Percutaneous endoscopic gastrostomy prior to esophagectomy for esophageal cancer - a systematic review and meta-analysis.

BACKGROUND: For resectable esophageal cancer (EC), it remains controversial whether to place percutaneous endoscopic gastrostomy (PEG) before the curative surgery to provide nutritional support during the neoadjuvant therapy. OBJECTIVE: To compare surgical outcomes for patients who received preoperative PEG and those without PEG placement (No-PEG) insertion prior to surgery in a potentially operable EC. METHODS: A comprehensive literature search was conducted to identify randomized and non-randomized studies comparing PEG and No-PEG groups. RESULTS: Four retrospective studies with a total number of 1,027 patients were identified and included in this meta-analysis. The differences in anastomotic leakage, anastomotic stricture, morbidity, pulmonary complications, wound infection, and hospital stay were not statistically significant between the two groups. Operation time was significantly shorter in the PEG group. There was no PEG-related gastric conduit failure and no leak from the PEG site in the PEG group. CONCLUSION: We conclude preoperative PEG for resectable EC is a safe procedure with no adverse effect on the gastric tube construction and anastomosis, it can be selectively inserted for EC patients with marked weight loss and malnutrition or those at risk of developing malnutrition during neoadjuvant therapy.

Roles of reactive oxygen species, mitochondrial membrane potential, and p53 in evodiamine-induced apoptosis and G2/M arrest of human anaplastic thyroid carcinoma cells.

BACKGROUND: Our previous studies have shown that evodiamine (EVO) as paclitaxel and nocodazole could trigger apoptosis in various human cancer cells including human renal cell carcinoma cells, colorectal carcinoma cells, and glioblastoma cells. This study aims to investigate the anti-cancer effects of EVO on human anaplastic thyroid carcinoma (ATC) cells, and underlining mechanism. METHODS: Two different endogenous p53 status human anaplastic thyroid carcinoma (ATC) cells including SW1736 (wtp53) and KAT4B (mutp53) were applied in the present study. The cytotoxicity of EVO on ATC cells was measured by MTT assay, and apoptosis and G2/M arrest were detected by propidium iodide (PI) staining followed by flow cytometry. Expression of indicated proteins was evaluated by Western blotting analysis, and pharmacological studies using chemical inhibitors and siRNA were performed for elucidating underlying mechanism. The roles of mitochondrial membrane potential and reactive oxygen species were investigated by flow cytometry using DiOC6 and DCFH-DA dye, respectively. RESULTS: SW1736 (wtp53) cells showed a higher apoptotic percentage than KAT4B (mutp53) cells in response to EVO stimulation via a flow cytometric analysis. Mechanistic studies showed that increased p53 and its downstream proteins, and disrupted MMP with increased intracellular peroxide production participated in EVO-induced apoptosis and G2/M arrest of SW1736 cells. In EVO-treated KAT4B cells, significant increases in G2/M percentage but little apoptotic events by EVO was observed. Structure-activity analysis showed that an alkyl group at position 14 was critical for induction of apoptosis related to ROS production and MMP disruption in SW1736 cells. CONCLUSION: Evidence indicated that the endogenous p53 status affected the sensitivity of ATC cells to EVO-induced apoptosis and G2/M arrest, revealing the potential role of p53 related to increased ROS production and disrupted MMP in the anticancer actions of EVO, and alkylation at position 14 of EVO is a critical substitution for apoptosis of ATC cells.