Defining the biogeographical map and potential bacterial translocation of microbiome in human 'surface organs'.

The microbiome in a specific human organ has been well-studied, but few reports have investigated the multi-organ microbiome as a whole. Here, we aim to analyse the intra-individual inter-organ and intra-organ microbiome in deceased humans. We collected 1608 samples from 53 sites of 7 surface organs (oral cavity, esophagus, stomach, small intestine, appendix, large intestine and skin; n = 33 subjects) and performed microbiome profiling, including 16S full-length sequencing. Microbial diversity varied dramatically among organs, and core microbial species co-existed in different intra-individual organs. We deciphered microbial changes across distinct intra-organ sites, and identified signature microbes, their functional traits, and interactions specific to each site. We revealed significant microbial heterogeneity between paired mucosa-lumen samples of stomach, small intestine, and large intestine. Finally, we established the landscape of inter-organ relationships of microbes along the digestive tract. Therefore, we generate a catalogue of bacterial composition, diversity, interaction, functional traits, and bacterial translocation in human at inter-organ and intra-organ levels.

Isolation, antibacterial characterization, and alternating tangential flow-based preparation of viable cells of Lacticaseibacillus paracasei XLK 401: Potential application in milk preservation.

It is desirable to obtain high levels of viable Lacticaseibacillus paracasei, a widely used food probiotic whose antibacterial activity and potential application in milk remain largely uninvestigated. Here, we isolated and purified the L. paracasei strain XLK 401 from food-grade blueberry ferments and found that it exhibited strong antibacterial activity against both gram-positive and gram-negative foodborne pathogens, including Staphylococcus aureus, Salmonella paratyphi B, Escherichia coli O157, and Shigella flexneri. Then, we applied alternating tangential flow (ATF) technology to produce viable L. paracasei XLK 401 cells and its cell-free supernatant (CFS). Compared with the conventional fed-batch method, 22 h of ATF-based processing markedly increased the number of viable cells of L. paracasei XLK 401 to 12.14 ± 0.13 log cfu/mL. Additionally, the CFS exhibited good thermal stability and pH tolerance, inhibiting biofilm formation in the abovementioned foodborne pathogens. According to liquid chromatography-mass spectrometry analysis, organic acids were the main antibacterial components of XLK 401 CFS, accounting for its inhibition activity. Moreover, the CFS of L. paracasei XLK 401 effectively inhibited the growth of multidrug-resistant gram-positive Staph. aureus and gram-negative E. coli O157 pathogens in milk, and caused a reduction in the pathogenic cell counts by 6 to 7 log cfu/mL compared with untreated control, thus considerably maintaining the safety of milk samples. For the first time to our knowledge, ATF-based technology was employed to obtain viable L. paracasei on a large scale, and its CFS could serve as a broad-spectrum biopreservative for potential application against foodborne pathogens in milk products.

Clinical features, prognostic stratification, and treatment of advanced-stage non-nasal type extranodal natural killer/T-cell lymphoma: a multi-institutional real-world study.

The present study aimed to investigate the clinical features, prognosis, and treatment of advanced-stage non-nasal type extranodal natural killer/T-cell lymphoma (ENKTCL). This real-world study retrospectively reviewed 56 newly diagnosed advanced-stage non-nasal type ENKTCL patients from two large-scale Chinese cancer centers in the last 10-15 years and screened 139 newly diagnosed advanced-stage nasal type ENKTCLs admitted during the same period for comparison. The non-nasal type ENKTCLs exhibited significantly higher Ki-67 expression levels compared to nasal type disease (P = 0.011). With a median follow-up duration of 75.03 months, the non-nasal group showed slightly inferior survival outcomes without statistically significant differences compared to the nasal group (median overall survival (OS): 14.57 vs. 21.53 months, 5-year OS: 28.0% vs. 38.5%, P = 0.120). Eastern Cooperative Oncology Group (ECOG) score ≥ 2 (hazard ratio (HR) = 2.18, P = 0.039) and lactic dehydrogenase (LDH) elevation (HR = 2.44, P = 0.012) were significantly correlated with worse OS in the non-nasal group. First-line gemcitabine-based chemotherapy regimens showed a trend toward slightly improved efficacy and survival outcomes compared to non-gemcitabine-based ones in the present cohort of non-nasal ENKTCLs (objective response rate: 91.7% vs. 63.6%, P = 0.144; complete response rate: 50.0% vs. 33.3%, P = 0.502; median progression-free survival: 10.43 vs. 3.40 months, P = 0.106; median OS: 25.13 vs. 9.30 months, P = 0.125), which requires further validation in larger sample size studies. Advanced-stage non-nasal type patients could achieve comparable prognosis with nasal cases after rational therapy. The modified nomogram-revised index (including age, ECOG score, and LDH) and modified international prognostic index (including age, ECOG score, LDH, and number of extranodal involvement) functioned effectively for prognostic stratification in non-nasal type ENKTCLs.

[Establishment of comprehensive evaluation models of physical fitness of the elderly based on machine learning].

The present study aims to establish comprehensive evaluation models of physical fitness of the elderly based on machine learning, and provide an important basis to monitor the elderly's physique. Through stratified sampling, the elderly aged 60 years and above were selected from 10 communities in Nanchang City. The physical fitness of the elderly was measured by the comprehensive physical assessment scale based on our previous study. Fuzzy neural network (FNN), support vector machine (SVM) and random forest (RF) models for comprehensive physical evaluation of the elderly people in communities were constructed respectively. The accuracy, sensitivity and specificity of the comprehensive physical fitness evaluation models constructed by FNN, SVM and RF were above 0.85, 0.75 and 0.89, respectively, with the FNN model possessing the best prediction performance. FNN, RF and SVM models are valuable in the comprehensive evaluation and prediction of physical fitness, which can be used as tools to carry out physical evaluation of the elderly.

Efficacy of high-fidelity simulation in advanced life support training: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Simulation is an increasingly used novel method for the education of medical professionals. This study aimed to systematically review the efficacy of high-fidelity (HF) simulation compared with low-fidelity (LF) simulation or no simulation in advanced life support (ALS) training. METHODS: A comprehensive search of the PubMed, Chinese Biomedicine Database, Embase, CENTRAL, ISI, and China Knowledge Resource Integrated Database was performed to identify randomized controlled trials (RCTs) that evaluated the use of HF simulation in ALS training. Quality assessment was based on the Cochrane Handbook for Systematic Reviews of Interventions version 5.0.1. The primary outcome was the improvement of knowledge and skill performance. The secondary outcomes included the participants' confidence and satisfaction at the course conclusion, skill performance at one year, skill performance in actual resuscitation, and patient outcomes. Data were synthesized using the RevMan 5.4 software. RESULTS: Altogether, 25 RCTs with a total of 1,987 trainees were included in the meta-analysis. In the intervention group, 998 participants used HF manikins, whereas 989 participants received LF simulation-based or traditional training (classical training without simulation). Pooled data from the RCTs demonstrated a benefit in improvement of knowledge [standardized mean difference (SMD) = 0.38; 95% confidence interval (CI): 0.18-0.59, P = 0.0003, I2 = 70%] and skill performance (SMD = 0.63; 95% CI: 0.21-1.04, P = 0.003, I2 = 92%) for HF simulation when compared with LF simulation and traditional training. The subgroup analysis revealed a greater benefit in knowledge with HF simulation compared with traditional training at the course conclusion (SMD = 0.51; 95% CI: 0.20-0.83, P = 0.003, I2 = 61%). Studies measuring knowledge at three months, skill performance at one year, teamwork behaviors, participants' satisfaction and confidence demonstrated no significant benefit for HF simulation. CONCLUSIONS: Learners using HF simulation more significantly benefited from the ALS training in terms of knowledge and skill performance at the course conclusion. However, further research is necessary to enhance long-term retention of knowledge and skill in actual resuscitation and patient's outcomes.

Intensive therapy can improve long-term survival in newly diagnosed, advanced-stage extranodal NK/T-cell lymphoma: A multi-institutional, real-world study.

The study investigated the treatment and prognosis of advanced-stage extranodal natural killer/T-cell lymphoma (ENKTL). With a median follow-up of 75.03 months, the median overall survival (mOS) for the 195 newly diagnosed stage III/IV ENKTL patients was 19.43 months, and estimated 1-, 2-, 3- and 5-year OS were 59.5%, 46.3%, 41.8% and 35.1%, respectively. Chemotherapy (CT) + radiotherapy (RT) compared to CT alone (P = .007), and hematopoietic stem cell transplantation (HSCT) compared to non-HSCT (P < .001), both improved OS. For patients ≤60 years and ineligible for HSCT, other therapies with complete remission led to comparable OS (P = .141). Nine patients ever treated with chidamide achieved a median progression-free survival (mPFS) and mOS of 53.63 (range, 3.47-92.33) and 54.80 (range, 5.50-95.70) months, and four with chidamide maintenance therapy (MT) achieved a mPFS and mOS of 55.83 (range, 53.27-92.33) and 60.65 (range, 53.70-95.70) months, possibly providing an alternative option for non-HSCT patients. Non-anthracycline (ANT)- compared to ANT-, asparaginase (Aspa)- compared to non-Aspa- and gemcitabine (Gem)- compared to non-Gem-based regimens, prolonged PFS (P = .031; P = .005; P = .009) and OS (P = .010; P = .086; P = .003), respectively. Multivariate analysis demonstrated that Gem-based regimens improved PFS (HR = 0.691, P = .061) and OS (HR = 0.624, P = .037). Gem + Aspa combinations slightly improved PFS and OS compared to regimens containing Gem or Aspa alone (P > 0.05). First-line "intensive therapy," including CT (particularly Gem + Aspa regimens), RT, HSCT and alternative chidamide MT, was proposed and could improve long-term survival for advanced-stage ENKTLs. Ongoing prospective clinical studies may shed further light on the value of chidamide MT.

Carnobacterium maltaromaticum boosts intestinal vitamin D production to suppress colorectal cancer in female mice.

Carnobacterium maltaromaticum was found to be specifically depleted in female patients with colorectal cancer (CRC). Administration of C. maltaromaticum reduces intestinal tumor formation in two murine CRC models in a female-specific manner. Estrogen increases the attachment and colonization of C. maltaromaticum via increasing the colonic expression of SLC3A2 that binds to DD-CPase of this bacterium. Metabolomic and transcriptomic profiling unveils the increased gut abundance of vitamin D-related metabolites and the mucosal activation of vitamin D receptor (VDR) signaling in C. maltaromaticum-gavaged mice in a gut microbiome- and VDR-dependent manner. In vitro fermentation system confirms the metabolic cross-feeding of C. maltaromaticum with Faecalibacterium prausnitzii to convert C. maltaromaticum-produced 7-dehydrocholesterol into vitamin D for activating the host VDR signaling. Overall, C. maltaromaticum colonizes the gut in an estrogen-dependent manner and acts along with other microbes to augment the intestinal vitamin D production to activate the host VDR for suppressing CRC.

Potential role of quorum quenching activity of silver nanoparticles in controlling non-filamentous bulking within activated sludge process.

The effective prevention and control of non-filamentous bulking is a significant challenge. In this study, the underlying effect of quorum sensing (QS) on inducing non-filamentous bulking and the maintenance effect of silver nanoparticles (AgNPs) on sludge floc stability, aggregation and settleability based on the quorum quenching (QQ) activity during non-filamentous bulking were investigated. The results showed that the concentration of N-acyl homoserine lactone (AHL) increased significantly in the activated sludge system at a high organic load rate (OLR), triggering the AHL-mediated QS. Additionally, the triggered QS promoted exopolysaccharide secretion, reducing the surface charge and hydrophobicity of the sludge aggregates, and further deteriorating the settleability of the sludge aggregates. AgNPs, a quorum sensing inhibitor (QSI), inhibited the AHL-QS based on QQ activity under high OLR, which maintained the physicochemical properties of extracellular polymeric substances (EPS). AgNPs-QQ maintained the surface energy barrier and electrostatic barrier of sludge aggregates and the gel properties of exopolysaccharides, which is favorable for microbial aggregation. The appropriate concentrations of AgNPs (≤10 mg/L) had no negative effect on biological nutrient removal in the sequencing batch reactors (SBRs) at the high organic loading. Therefore, AgNPs effectively prevent and control non-filamentous bulking by their QQ activity in the activated sludge process. Thus, the present study provided new insights into controlling non-filamentous bulking during the activated sludge process.

High Sensitivity of Shotgun Metagenomic Sequencing in Colon Tissue Biopsy by Host DNA Depletion.

The high host genetic background of tissue biopsies hinders the application of shotgun metagenomic sequencing in characterizing the tissue microbiota. We proposed an optimized method that removed host DNA from colon biopsies and examined the effect on metagenomic analysis. Human or mouse colon biopsies were divided into two groups, with one group undergoing host DNA depletion and the other serving as the control. Host DNAs were removed through differential lysis of mammalian and bacterial cells before sequencing. The impact of host DNA depletion on microbiota was compared based on phylogenetic diversity analyses and regression analyses. Removing host DNA enhanced bacterial sequencing depth and improved species discovery, increasing bacterial reads by 2.46 ± 0.20 fold while reducing host reads by 6.80% ± 1.06%. Moreover, 3.40 times more of bacterial species were detected after host DNA depletion. This was confirmed from mouse colon tissues, increasing bacterial reads by 5.46 ± 0.42 fold while decreasing host reads by 10.2% ± 0.83%. Similarly, significantly more species were detected in the mouse colon tissue upon host DNA depletion (P < 0.001). Furthermore, an increased microbial richness was evident in the host DNA-depleted samples compared with non-depleted controls in human colon biopsies and mouse colon tissues (P < 0.001). Our optimized method of host DNA depletion improved the sensitivity of shotgun metagenomic sequencing in bacterial detection in the biopsy, which may yield a more accurate taxonomic profile of the tissue microbiota and identify bacteria that are important for disease initiation or progression.

A contribution to the genus Didrepanephorus Wood-Mason, 1878 (Coleoptera, Scarabaeidae, Rutelinae).

The diagnostic characters of the genera Didrepanephorus Wood-Mason, 1878 and Fruhstorferia Kolbe, 1894 are clarified. The following nomenclatorial acts are proposed: Didrepanephorusbirmanicus (Arrow, 1907), comb. nov., Didrepanephorusfukinukii (Muramoto & Araya, 2000), comb. nov., Fruhstorferiabaron (Prokofiev, 2013), comb. nov., and Fruhstorferiaanthracina Ohaus, 1903, comb. rev. Didrepanephorustangzhaoyangi Zhao & Liu, sp. nov. is described from Yunnan Province, China. A lectotype is designated for Fruhstorferiabirmanica Arrow, 1907. Didrepanephorusmizunumai Nagai & Hirasawa, 1991 is reported from Myanmar for the first time.

Cryoprotective effect of antifreeze protein III on the rabbit ovary.

CONTEXT: Ovarian tissue cryopreservation is effective in preserving fertility in cancer patients who have concerns about fertility loss due to cancer treatment. However, ischemia reduces the lifespan of grafts. Microvascular transplantation of cryopreserved whole ovary may allow immediate revascularisation, but the damage incurred during the cryopreservation procedure may cause follicular depletion; hence, preventing chilling injury would help maintain ovarian function. AIM: This study was designed to investigate the beneficial effects of antifreeze protein III (AFP III) on rabbit ovary cryopreservation. METHODS: Ovaries (n =25) obtained from 5-month-old female rabbits (n =13) were frozen by slow freezing and vitrification. Cryoprotectant media were supplemented with and without 1mg/mL of AFP III. The experiment was divided into five groups: fresh control group (F), slow freezing group (S), slow freezing group with AFP III (AFP III-S), vitrification group (V) and vitrification group with AFP III (AFP III-V). All groups of ovaries were examined by histological characteristics analysis, ultrastructural analysis, apoptosis detection and follicle viability test. KEY RESULTS: With slow freezing, the normal rate of change in follicle morphology, density of stromal cells and the survival rate of follicles in the AFP III supplemented group were significantly higher than those in the non-supplemented group, and a lower oocyte apoptotic rate was shown in the AFP III supplemented group. In the vitrification groups, the normal rate of change in follicle morphology and density of stromal cells in the AFP III supplemented group were significantly higher than those in the non-supplemented group, and a lower oocyte apoptotic rate was found in the AFP III supplemented group. But there was no obvious difference in the survival rate of follicles between the two groups. There was also no significant difference in the normal rate of change in follicle morphology, the survival rate of follicles and the apoptotic rate of oocytes between the vitrification and slow freezing groups (P >0.05), but the density of stromal cells in the vitrification groups was statistically higher than that of the slow freezing group (P <0.05). CONCLUSIONS: The addition of AFP III in slow freezing and vitrification could improve the cryoprotective effect of ovaries, which was more evident in slow freezing. IMPLICATIONS: The findings of this study provide a foundation for further research on the effects of AFP III in human ovarian tissue.

Revision of the javanicus species group of the millipede genus Glyphiulus Gervais, 1847, with descriptions of five new species from China (Diplopoda, Spirostreptida, Cambalopsidae).

The javanicus-group of Glyphiulus is re-assessed and its Chinese component species are presently divided between the following two newly-circumscribed species groups, i.e. the formosus- and the sinensis-group. The two can be differentiated, based on the diagnostic characters of the first pair of legs in the male. In addition, metatergal crests being complete and the carinotaxy formula on the collum being I-III+P+M are only characteristic of the formosus-group. A molecular phylogeny of the genus, based on DNA sequencing of four gene fragments of four genes, allows for Glyphiulus to be recovered as a monophyletic group, the phylogenetic relationship being ((Clade A, Clade B), Clade C). Molecular evidence is fully congruent with the morphological one. In addition, based on barcoding data, interspecific p-distances between Glyphiulus species amount to 11.2-24.9%, vs. 0-8.2% for intraspecific p-distances. Five new species of Glyphiulus, all cavernicolous, are described from China: G.sinuatoprocessus Zhao & Liu, sp. nov., G.conuliformis Zhao & Liu, sp. nov. (both from Guangdong Province), G.xiniudong Zhao & Liu, sp. nov., G.scutatus Zhao & Liu, sp. nov. and G.portaliformis Zhao & Liu, sp. nov. (all three from Guangxi Zhuang Autonomous Region). The known Chinese species of the formosus-group appear to mainly be confined to the South China region.

Streptococcus thermophilus Inhibits Colorectal Tumorigenesis Through Secreting ß-Galactosidase.

BACKGROUND & AIMS: Streptococcus thermophilus was identified to be depleted in patients with colorectal cancer (CRC) by shotgun metagenomic sequencing of 526 multicohort fecal samples. Here, we aim to investigate whether this bacterium could act as a prophylactic for CRC prevention. METHODS: The antitumor effects of S thermophilus were assessed in cultured colonic epithelial cells and in 2 murine models of intestinal tumorigenesis. The tumor-suppressive protein produced by S thermophilus was identified by mass spectrometry and followed by ß-galactosidase activity assay. The mutant strain of S thermophilus was constructed by homologous recombination. The effect of S thermophilus on the gut microbiota composition was assessed by shotgun metagenomic sequencing. RESULTS: Oral gavage of S thermophilus significantly reduced tumor formation in both Apcmin/+ and azoxymethane-injected mice. Coincubation with S thermophilus or its conditioned medium decreased the proliferation of cultured CRC cells. ß-Galactosidase was identified as the critical protein produced by S thermophilus by mass spectrometry screening and ß-galactosidase activity assay. ß-Galactosidase secreted by S thermophilus inhibited cell proliferation, lowered colony formation, induced cell cycle arrest, and promoted apoptosis of cultured CRC cells and retarded the growth of CRC xenograft. The mutant S thermophilus without functional ß-galactosidase lost its tumor-suppressive effect. Also, S thermophilus increased the gut abundance of known probiotics, including Bifidobacterium and Lactobacillus via ß-galactosidase. ß-Galactosidase-dependent production of galactose interfered with energy homeostasis to activate oxidative phosphorylation and downregulate the Hippo pathway kinases, which partially mediated the anticancer effects of S thermophilus. CONCLUSION: S thermophilus is a novel prophylactic for CRC prevention in mice. The tumor-suppressive effect of S thermophilus is mediated at least by the secretion of ß-galactosidase.

Characterization of coal-based fulvic acid and the construction of a fulvic acid molecular model.

Fulvic acid (FA) is important in modern agriculture, ecological restoration, life science, and medicine. The precise characterization of the composition and molecular structure of FA has become a key scientific issue in both basic and applied research. In this study, coal-based FA was separated by microwave-assisted oxygenation from lignite originating from Inner Mongolia in China. Through elemental analysis, infrared spectroscopy, nuclear magnetic resonance spectroscopy, classical quantitative titration experiments, and quantum chemistry combined with software analysis, the representative microscopic molecular structure of FA was determined. The results show that coal-based FA mainly contains three kinds of benzene ring substituents, ether bonds, hydrogen bonds, carbonyl groups, hydroxyl groups, carboxyl groups, phenolic hydroxyl groups, and semiquinonyl groups. The oxygen content is high, the carbon-to-oxygen ratio is less than 1, and the hydrogen-to-carbon ratio is 1.09. The ratio of aromatic carbon to total carbon is approximately 0.6, and benzene rings are connected to each other by an ether-oxygen bridge. The fat chain length of FA is approximately 0.47. FA has a small molecular structure with many acidic groups, primarily carboxyl groups and phenolic hydroxyl groups. The two-dimensional planar molecular structure of FA was established; the chemical formula is C38H32NO24, and the relative molecular mass is 886. The lowest-energy, structurally optimized three-dimensional characteristic ball-and-stick and stick models were also constructed. The calculated infrared spectrum of the molecular structure matches well with the experimental spectrum of FA, and the types and distributions of functional groups agree with the findings of previous studies. The quantum chemical data confirm that the proposed molecular structure is reasonable. The findings provide a scientific reference for applied research on FA in the future.

Effect of age as a continuous variable on survival outcomes and treatment selection in patients with extranodal nasal-type NK/T-cell lymphoma from the China Lymphoma Collaborative Group (CLCG).

PURPOSE: The aim of this study was to determine the impact of analyzing age as a continuous variable on survival outcomes and treatment selection for extranodal nasal-type NK/T-cell lymphoma. RESULTS: The risk of mortality increased with increasing age, without an apparent cutoff point. Patients' age, as a continuous variable, was independently associated with overall survival after adjustment for covariates. Older early-stage patients were more likely to receive radiotherapy only whereas young-adult advanced-stage patients tended to receive non-anthracycline-based chemotherapy. A decreased risk of mortality with radiotherapy versus chemotherapy only in early-stage patients (HR, 0.347, P < 0.001) or non-anthracycline-based versus anthracycline-based chemotherapy in early-stage (HR, 0.690, P = 0.001) and advanced-stage patients (HR, 0.678, P = 0.045) was maintained in patients of all ages. CONCLUSIONS: These findings support making treatment decisions based on disease-related risk factors rather than dichotomized chronological age. PATIENTS AND METHODS: Data on 2640 patients with extranodal nasal-type NK/T-cell lymphoma from the China Lymphoma Collaborative Group database were analyzed retrospectively. Age as a continuous variable was entered into the Cox regression model using penalized spline analysis to determine the association of age with overall survival (OS) and treatment benefits.

Dysfunction of PLA2G6 and CYP2C44-associated network signals imminent carcinogenesis from chronic inflammation to hepatocellular carcinoma.

Little is known about how chronic inflammation contributes to the progression of hepatocellular carcinoma (HCC), especially the initiation of cancer. To uncover the critical transition from chronic inflammation to HCC and the molecular mechanisms at a network level, we analyzed the time-series proteomic data of woodchuck hepatitis virus/c-myc mice and age-matched wt-C57BL/6 mice using our dynamical network biomarker (DNB) model. DNB analysis indicated that the 5th month after birth of transgenic mice was the critical period of cancer initiation, just before the critical transition, which is consistent with clinical symptoms. Meanwhile, the DNB-associated network showed a drastic inversion of protein expression and coexpression levels before and after the critical transition. Two members of DNB, PLA2G6 and CYP2C44, along with their associated differentially expressed proteins, were found to induce dysfunction of arachidonic acid metabolism, further activate inflammatory responses through inflammatory mediator regulation of transient receptor potential channels, and finally lead to impairments of liver detoxification and malignant transition to cancer. As a c-Myc target, PLA2G6 positively correlated with c-Myc in expression, showing a trend from decreasing to increasing during carcinogenesis, with the minimal point at the critical transition or tipping point. Such trend of homologous PLA2G6 and c-Myc was also observed during human hepatocarcinogenesis, with the minimal point at high-grade dysplastic nodules (a stage just before the carcinogenesis). Our study implies that PLA2G6 might function as an oncogene like famous c-Myc during hepatocarcinogenesis, while downregulation of PLA2G6 and c-Myc could be a warning signal indicating imminent carcinogenesis.

Chymase inhibitor TY-51469 in therapy of inflammatory bowel disease.

AIM: To investigate the effect of chymase inhibitor TY-51469 in the therapy of inflammatory bowel disease and the underlying mechanism. METHODS: Seventy-five healthy Sprague-Dawley rats were randomly assigned to one of the three groups (control group, model group and TY-51469 experiment group) and each group had twenty-five rats. The rats of the model group and experiment group were subjected to treatment with 3.5% dextran sulfate sodium (DSS) 10 mg/kg to induce colitis. The control group and model group were subjected to intraperitoneal injection of saline, while the experiment group was subjected to intraperitoneal injection of 10 mg/kg TY-51469 each day. Five rats of each group were sacrificed on 0, 7, 14, 21 and 28 d, respectively. The degree of inflammation was assessed by histopathological scoring; flow cytometry was performed to detect the proportion of CD4(+)CD25(+) Tregs in peripheral blood; colon tissues of rats were collected to measure mRNA and protein expression by PCR, Western blot and immunohistochemistry; serum levels of interleukin (IL)-10, transforming growth factor (TGF)-ß1 and IL-17A were detected by ELISA. RESULTS: The rats in the experiment group and model group had significantly more severe colitis than the ones in the control group (P < 0.05) before treatment on day 0; no significant difference was observed between the experiment group and model group (P > 0.05). After treatment with TY-51469, the rats in the experiment group had significantly less severe colitis compared with the model group on 7, 14, 21 and 28 d (P < 0.05). The proportion of CD4(+)CD25(+) Tregs was lower in the model group and experiment group than in the control group; the experiment group had a significantly higher proportion of CD4(+)CD25(+) Tregs than that in the model group (P < 0.05). The model group and experiment group demonstrated lower expression of Foxp3 than the control group; the experiment group had higher Foxp3 expression than the model group (P < 0.05). Cytokines IL-10, TGF-ß1 and IL-17A were lower in the model group and experiment group than in the control group; the experiment group had higher expression than the model group (P < 0.05). CONCLUSION: After treatment with chymase inhibitor TY-51469, the experiment group demonstrated more significantly reduced intestinal inflammation and higher expression of immune tolerance related cytokines (IL-10, TGF-ß1, IL-17A) and Foxp3 which is specifically expressed in Tregs compared with the model group. Therefore, chymase inhibitor TY-51469 might ameliorate the progression of DSS-induced colitis possibly by increasing the expression of Tregs and cytokines.

Predicting cancerlectins by the optimal g-gap dipeptides.

The cancerlectin plays a key role in the process of tumor cell differentiation. Thus, to fully understand the function of cancerlectin is significant because it sheds light on the future direction for the cancer therapy. However, the traditional wet-experimental methods were money- and time-consuming. It is highly desirable to develop an effective and efficient computational tool to identify cancerlectins. In this study, we developed a sequence-based method to discriminate between cancerlectins and non-cancerlectins. The analysis of variance (ANOVA) was used to choose the optimal feature set derived from the g-gap dipeptide composition. The jackknife cross-validated results showed that the proposed method achieved the accuracy of 75.19%, which is superior to other published methods. For the convenience of other researchers, an online web-server CaLecPred was established and can be freely accessed from the website http://lin.uestc.edu.cn/server/CalecPred. We believe that the CaLecPred is a powerful tool to study cancerlectins and to guide the related experimental validations.

Anti-TNF-A therapy about infliximab and adalimamab for the effectiveness in ulcerative colitis compared with conventional therapy: a meta-analysis.

BACKGROUND/AIMS: TNF-α has an important role in the pathogenesis of ulcerative colitis (UC). It seems that anti-TNF-α therapy is beneficial in the treatment of UC. The aim was to assess the effectiveness of Infliximab and Adalimamab with UC compared with conventional therapy. METHODOLOGY: The Pubmed and Embase databases were searched for studies investigating the efficacy of infliximab and adalimumab on UC. RESULTS: Infliximab had a statistically significant effects in induction of clinical response (RR = 1.67; 95% CI 1.12 to 2.50) of UC compared with conventional therapy, but those had not a statistically significant effects in clinical remission (RR = 1.63; 95% CI 0.84 to 3.18) and reduction of colectomy rate (RR = 0.54; 95% CI 0.26 to 1.12) of UC. And adalimumab had a statistically significant effects in induction of clinical remission (RR = 1.82; 95% CI 1.24 to 2.67) and clinical response (RR = 1.36; 95% CI 1.13 to 1.64) of UC compared with conventional therapy. CONCLUSION: Our meta-analyses suggested that Infliximab had a statistically significant effects in induction of clinical response of UC compared with conventional therapy and adalimumab had a statistically significant effects in induction of clinical remission and clinical response of UC compared with conventional therapy.