Dietary fibre supplementation enhances radiotherapy tumour control and alleviates intestinal radiation toxicity.

Background: Non-toxic approaches to enhance radiotherapy outcomes are beneficial, particularly in ageing populations. Based on preclinical findings showing that high-fibre diets sensitised bladder tumours to irradiation by modifying the gut microbiota, along with clinical evidence of prebiotics enhancing anti-cancer immunity, we hypothesised that dietary fibre and its gut microbiota modification can radiosensitise tumours via secretion of metabolites and/or immunomodulation. We investigated the efficacy of high-fibre diets combined with irradiation in immunoproficient C57BL/6 mice bearing bladder cancer flank allografts.

Venomous gland transcriptome and venom proteomic analysis of the scorpion Androctonus amoreuxi reveal new peptides with anti-SARS-CoV-2 activity.

The recent COVID-19 pandemic shows the critical need for novel broad spectrum antiviral agents. Scorpion venoms are known to contain highly bioactive peptides, several of which have demonstrated strong antiviral activity against a range of viruses. We have generated the first annotated reference transcriptome for the Androctonus amoreuxi venom gland and used high performance liquid chromatography, transcriptome mining, circular dichroism and mass spectrometric analysis to purify and characterize twelve previously undescribed venom peptides.

Homemade Nucleic Acid Preservation Buffer Proves Effective in Preserving the Equine Faecal Microbiota over Time at Ambient Temperatures.

The equine faecal microbiota is often assessed as a proxy of the microbial community in the distal colon, where the microbiome has been linked to states of health and disease in the horse. However, the microbial community structure may change over time if samples are not adequately preserved. This study stored equine faecal samples from = 10 horses in four preservation treatments at room temperature for up to 150 h and assessed the resulting impact on microbial diversity and the differential abundance of taxa.

Taxonomy of fibroblasts and progenitors in the synovial joint at single-cell resolution.

Objectives: Fibroblasts in synovium include fibroblast-like synoviocytes (FLS) in the lining and + connective-tissue fibroblasts in the sublining. We aimed to investigate their developmental origin and relationship with adult progenitors.

Methods: To discriminate between -lineage cells deriving from the embryonic joint interzone and other -expressing fibroblasts and progenitors, adult mice were used and cartilage injury was induced to activate progenitors.

β-Glucan is a major growth substrate for human gut bacteria related to Coprococcus eutactus.

A clone encoding carboxymethyl cellulase activity was isolated during functional screening of a human gut metagenomic library using Lactococcus lactis MG1363 as heterologous host. The insert carried a glycoside hydrolase family 9 (GH9) catalytic domain with sequence similarity to a gene from Coprococcus eutactus ART55/1. Genome surveys indicated a limited distribution of GH9 domains among dominant human colonic anaerobes.

VGLL3 operates via TEAD1, TEAD3 and TEAD4 to influence myogenesis in skeletal muscle.

VGLL proteins are transcriptional co-factors that bind TEAD family transcription factors to regulate events ranging from wing development in fly, to muscle fibre composition and immune function in mice. Here, we characterise in skeletal muscle. We found that mouse was expressed at low levels in healthy muscle but that its levels increased during hypertrophy or regeneration; in humans, was highly expressed in tissues from patients with various muscle diseases, such as in dystrophic muscle and alveolar rhabdomyosarcoma.

Formate cross-feeding and cooperative metabolic interactions revealed by transcriptomics in co-cultures of acetogenic and amylolytic human colonic bacteria.

Interspecies cross-feeding is a fundamental factor in anaerobic microbial communities. In the human colon, formate is produced by many bacterial species but is normally detected only at low concentrations. Ruminococcus bromii produces formate, ethanol and acetate in approximately equal molar proportions in pure culture on RUM-RS medium with 0.

Adaptive response of neonatal sepsis-derived Group B Streptococcus to bilirubin.

Hyperbilirubinemia is so common in newborns as to be termed physiological. The most common bacteria involved in early-onset neonatal sepsis are Streptococcus agalactiae, commonly called Group B Streptococcus (GBS). Whilst previous studies show bilirubin has antioxidant properties and is beneficial in endotoxic shock, little thought has been given to whether bilirubin might have antibacterial properties.

Common and Distinctive Functions of the Hippo Effectors Taz and Yap in Skeletal Muscle Stem Cell Function.

Hippo pathway downstream effectors Yap and Taz play key roles in cell proliferation and regeneration, regulating gene expression especially via Tead transcription factors. To investigate their role in skeletal muscle stem cells, we analyzed Taz in vivo and ex vivo in comparison with Yap. Small interfering RNA knockdown or retroviral-mediated expression of wild-type human or constitutively active TAZ mutants in satellite cells showed that TAZ promoted proliferation, a function shared with YAP.

Fine-mapping of genes determining extrafusal fiber properties in murine soleus muscle.

Muscle fiber cross-sectional area (CSA) and proportion of different fiber types are important determinants of muscle function and overall metabolism. Genetic variation plays a substantial role in phenotypic variation of these traits; however, the underlying genes remain poorly understood. This study aimed to map quantitative trait loci (QTL) affecting differences in soleus muscle fiber traits between the LG/J and SM/J mouse strains.

Regulation of cellular sphingosine-1-phosphate by sphingosine kinase 1 and sphingosine-1-phopshate lyase determines chemotherapy resistance in gastroesophageal cancer.

Background: Resistance to chemotherapy is common in gastroesophageal cancer. Mechanisms of resistance are incompletely characterised and there are no predictive biomarkers in clinical practice for cytotoxic drugs. We used new cell line models to characterise novel chemotherapy resistance mechanisms and validated them in tumour specimens to identify new targets and biomarkers for gastroesophageal cancer.

Tumour expression of leptin is associated with chemotherapy resistance and therapy-independent prognosis in gastro-oesophageal adenocarcinomas.

Background: Cytotoxic chemotherapy remains the main systemic therapy for gastro-oesophageal adenocarcinoma, but resistance to chemotherapy is common, resulting in ineffective and often toxic treatment for patients. Predictive biomarkers for chemotherapy response would increase the probability of successful therapy, but none are currently recommended for clinical use. We used global gene expression profiling of tumour biopsies to identify novel predictive biomarkers for cytotoxic chemotherapy.

Influence of resistance to 5-fluorouracil and tomudex on [18F]‑FDG incorporation, glucose transport and hexokinase activity.

Drug resistance is a major obstacle to cancer cure and may influence [18F]-fluorodeoxyglucose (FDG) incorporation. In this study, glucose transport, hexokinase activity and [18F]-FDG incorporation were measured in drug-resistant tumour cells generated by exposing H630 colon and MCF7 breast cancer cells to increasing concentrations of tomudex (raltitrexed) or 5-fluorouracil (5FU). Drug sensitivity was determined using the XTT assay: Tomudex-resistant (H630TDX and MCF7TDX) cells were more than 40,000-fold less sensitive to tomudex than were the parental wild-type, H630WT and MCF7WT cells, respectively.

SerpinB3, a new prognostic tool in breast cancer patients treated with neoadjuvant chemotherapy.

It is unclear which patients with breast cancer benefit from anthracycline-based neoadjuvant chemotherapy and whether taxanes increase survival. Hsp70 and serpinB3 inhibit a lysosomal cell death pathway induced in anthracycline and taxane treated cells, which may be critical for breast cancer cell survival. Thus we evaluated serpinB3 and Hsp70 as putative prognostic biomarkers in breast cancer patients treated with neoadjuvant chemotherapy.

APRIL is a novel clinical chemo-resistance biomarker in colorectal adenocarcinoma identified by gene expression profiling.

Background: 5-Fluorouracil(5FU) and oral analogues, such as capecitabine, remain one of the most useful agents for the treatment of colorectal adenocarcinoma. Low toxicity and convenience of administration facilitate use, however clinical resistance is a major limitation. Investigation has failed to fully explain the molecular mechanisms of resistance and no clinically useful predictive biomarkers for 5FU resistance have been identified.

Balancing inflammatory, lipid, and xenobiotic signaling pathways by VSL#3, a biotherapeutic agent, in the treatment of inflammatory bowel disease.

Background: The interleukin 10 knockout mouse (IL10-KO) is a model of human inflammatory bowel disease (IBD) used to study host microbial interactions and the action of potential therapeutics. Using Affymetrix data analysis, important signaling pathways and transcription factors relevant to gut inflammation and antiinflammatory probiotics were identified.

Methods: Affymetrix microarray analysis on both wildtype (WT) and IL10-KO mice orally administered with and without the probiotic VSL#3 was performed and the results validated by real-time polymerase chain reaction (PCR), immunocytochemistry, proteomics, and histopathology.

Gene expression analysis of human fetal ovarian primordial follicle formation.

Context: Primordial follicle formation dictates the maximal potential female reproductive capacity and establishes the ovarian reserve. Currently, little is known about this process in the human.

Objective: The aim of the study was to identify genes associated with the onset of human fetal primordial follicle formation in morphologically normal human fetuses.

Cell cycle perturbation and acquired 5-fluorouracil chemoresistance.

Acquired chemoresistance is one of the obstacles for success of 5-fluorouracil (5-FU)-based cancer chemotherapy. Some molecular mechanisms of acquired 5-FU resistance are still unknown. We have recently demonstrated down-regulation of a group of cell cycle related genes in acquired 5-FU resistant human cancer cell lines.

Decreased [18F]fluoro-2-deoxy-d-glucose incorporation and increased glucose transport are associated with resistance to 5FU in MCF7 cells in vitro.

Introduction: Tumor refractoriness to chemotherapy is frequently due to the acquisition of resistance. Resistant cells selected by exposure to chemotherapy agents may exhibit differences in [18F]fluoro-2-deoxy-d-glucose (FDG) incorporation, as compared with sensitive cells.

Methods: FDG incorporation, hexokinase (HK) activity, glucose transport and ATP content were determined in clones of 5-fluorouracil (5FU)-resistant MCF7 cells, established by long-term exposure to increasing 5FU concentrations, and in parental MCF7 cells.

Mechanisms of acquired chemoresistance to 5-fluorouracil and tomudex: thymidylate synthase dependent and independent networks.

Purpose: Thymidylate synthase (TS) over-expression is widely accepted as a major molecular mechanism responsible for 5-fluorouracil (5-FU) and tomudex (TDX) resistance. In this study, the importance of TS in 5-FU and TDX resistance was evaluated.

Methods: The sensitivity of TS-over-expressing 5-FU (3) and TDX (3) resistant cell lines to 5-FU and TDX was analysed.

Pregnane X receptor activators inhibit human hepatic stellate cell transdifferentiation in vitro.

Background & Aims: The activated pregnane X receptor is antifibrogenic in rodent chronic liver injury in vivo models. The aim of this study was to determine the effects of human pregnane X receptor activators on human hepatic stellate cell transdifferentiation to a profibrogenic phenotype in vitro.

Methods: Hepatic stellate cells were isolated from resected human liver and cultured under conditions in which they trans-differentiate into profibrogenic myofibroblasts.

Tumor transcriptome reveals the predictive and prognostic impact of lysosomal protease inhibitors in non-small-cell lung cancer.

Purpose: Insight into clinical response to platinum-based chemotherapy (PBC) in non-small-cell lung cancer (NSCLC).

Methods: Matched tumor and nontumor lung tissues from PBC-treated NSCLC patients (four nonresponders and four responders) and tumor tissue from an independent test set (four nonresponders and four responders), were profiled using microarrays. Lysosomal protease inhibitors SerpinB3 and cystatin C were highly correlated with clinical response and were further evaluated by immunohistochemistry in PBC-treated patients (36 prechemotherapy and 13 postchemotherapy).

Mechanistic and predictive profiling of 5-Fluorouracil resistance in human cancer cells.

Gene expression was analyzed in five pairs of 5-fluorouracil (5-FU) resistant and parental cancer cell lines on DNA microarrays. In unsupervised analysis, a prediction rule was built from the expression profiles of 29 genes, and 5-FU sensitivity class was predicted with 100% accuracy and high predictive strength. In supervised analysis of key 5-FU pathways, expression of 91 genes was associated with 5-FU sensitivity phenotype and segregated samples accordingly in hierarchical analysis.