CHI3L1 in the pathophysiology and diagnosis of liver diseases.

Chitinase 3-like protein 1(CHI3L1) participates in physiological and pathophysiological process, such as cell survival, cell proliferation, tissue remodeling, angiogenesis, etc. Some studies demonstrated that CHI3L1 is liver-enriched and has better application value in staging liver fibrosis than platelet ratio index(APRI) and fibrosis-4 index(FIB-4) and that CHI3L1 can be used in monitoring the prognosis of hepatocellular carcinoma (HCC). In this review, we summarized the pathophysiological role and the diagnostic value of CHI3L1 in liver fibrosis in different background and HCC.

Hippocampal neural stem cells facilitate access from circulation via apical cytoplasmic processes.

Blood vessels (BVs) are considered an integral component of neural stem cells (NSCs) niches. NSCs in the dentate gyrus (DG(have enigmatic elaborated apical cellular processes that are associated with BVs. Whether this contact serves as a mechanism for delivering circulating molecules is not known. Here we uncovered a previously unrecognized communication route allowing exclusive direct access of blood-borne substances to hippocampal NSCs. BBB-impermeable fluorescent tracer injected transcardially to mice is selectively uptaken by DG NSCs within a minute, via the vessel-associated apical processes. These processes, measured >30 nm in diameter, establish direct membrane-to-membrane contact with endothelial cells in specialized areas of irregular endothelial basement membrane and enriched with vesicular activity. Doxorubicin, a brain-impermeable chemotherapeutic agent, is also readily and selectively uptaken by NSCs and reduces their proliferation, which might explain its problematic anti-neurogenic or cognitive side-effect. The newly-discovered NSC-BV communication route explains how circulatory neurogenic mediators are 'sensed' by NSCs.

Terbium chloride influences Clostridium difficile spore germination.

The germination of Clostridium difficile spores is an important stage of the C. difficile life cycle. In other endospore-forming bacteria, the composition of the medium in which the spores are generated influences the abundance of germination-specific proteins, thereby influencing the sensitivity of the spores towards germinants. In C. difficile media composition on the spores has only been reported to influence the number of spores produced. One of the measures of spore germination is the analysis of the release of DPA from the spore core. To detect DPA release in real time, terbium chloride is often added to the germination conditions because Tb3+ complexes with the released DPA and this can be detected using fluorescence measurements. Although C. difficile spores germinate in response to TA and glycine, recently calcium was identified as an enhancer for spore germination. Here, we find that germination by spores prepared in peptone rich media, such as 70:30, is positively influenced by terbium. We hypothesize that, in these assays, Tb3+ functions similarly to calcium. Although the mechanism(s) causing increased sensitivity of the C. difficile spores that are prepared in peptone rich media to terbium is still unknown, we suggest that the TbCl3 concentration used in the analysis of C. difficile DPA release be carefully titrated so as not to misinterpret future findings.

Calcium mimics the chemotactic effect of conditioned media and is an effective inducer of bone regeneration.

BACKGROUND: After bone resorption, ions and degraded organic components are co-released into the extracellular space. Ions and growth factors, although different in their biological nature, induce a common and coordinated chemotactic effect. Conditioned media has been used successfully in bone regeneration by promoting endogenous cell recruitment. Likewise, calcium alone act as a paracrine chemotactic signal, inducing the host's undifferentiated progenitor cell infiltration into the implanted biomaterials. The aim of the present study was to compare the chemotactic effect of calcium and conditioned media in primary calvarial cells. METHODS: The chemotactic cell response was evaluated in vitro using an agarose spot and a wound healing assay. In addition, we used a calvarial bone explant model ex-vivo. The healing potential was also tested through an in vivo model, a critical-size calvarial bone defect in mice. For the in vivo experiment, cell-free calcium-containing or conditioned media-containing scaffolds were implanted, and MSC's seeded scaffolds were used as positive control. After seven weeks post-implantation, samples were retrieved, and bone regeneration was evaluated by µCT and histological analysis. Osteogenic gene expression was evaluated by qPCR. RESULTS: We found that chemotactic cell migration in response to either calcium or conditioned media was equivalent in vitro and ex vivo. Accordingly, µCT analysis showed that bone regeneration induced by the MSC's seeded scaffolds was similar to that obtained with cell-free calcium or conditioned media-containing scaffolds. Pre-treatment with SB202190, a highly selective p38 inhibitor, abrogated the chemotactic effect induced by conditioned media. In contrast, p38 activity was not essential for the calcium-induced chemotaxis. Moreover, BAPTA-AM treatment, a cytosolic calcium chelator, decreased the chemotactic effect and the expression of key osteogenic genes induced by calcium or conditioned media. CONCLUSION: We show that calcium ions alone not only mimic the conditioned media chemotactic effect, but also induce an osteogenic effect similar to that produced by transplanted MSC's in vivo. Furthermore, the chemotactic effect induced by conditioned media is calcium and p38 dependent. The rise in cytosolic calcium might integrate the different signaling pathways triggered by conditioned media and extracellular Ca2+. This calcium-driven in situ bone regeneration is a promising and convenient alternative to promote endogenous cell recruitment into the injured bone site. This pre-clinical cell-free and growth factor-free approach might avoid the disadvantages of the ex vivo cell manipulation.

Evaluation of the overall impact of antibiotics growth promoters on broiler health and productivity during the medication and withdrawal period.

The effectiveness of some common combination of antibiotic growth promoters (AGP) on growth performance, gut health, and meat quality was evaluated during the medication and withdrawal period in broilers. A total of 540 male Arbor Acre broilers at 0 D of age were randomly assigned to 5 treatments, with 6 replicates of 18 chicks. Broilers received diets during the medication period (0 to 42 D) as follows: NC (control diet without AGP), EN (NC + enduracidin 8 ppm + colistin sulfate 8 ppm), BZ (NC + bacitracin zinc 40 ppm + colistin sulfate 8 ppm), CT (NC + chlortetracycline 50 ppm + colistin sulfate 8 ppm), and VG (NC + virginiamycin 20 ppm + colistin sulfate 8 ppm). Broilers were switched to the same finisher diet without AGP during the withdrawal period (43 to 49 D). The feed:gain ratio in EN, BZ, CT, and VG groups were significantly decreased by 0.07, 0.10, 0.06, and 0.05 during 0 to 42 D (P < 0.05), but increased by 0.19 (P > 0.05), 0.33 (P > 0.05), 0.49 (P < 0.05), and 0.69 (P < 0.05) during the withdrawal period, respectively. The jejunum villus height (VH) increased in EN group (P < 0.05) and crypt depth (CD) reduced in BZ, CT, and VG groups (P < 0.05) at 42 D, while jejunum VH increased in EN and BZ groups (P < 0.05) at 49 D compared to NC group (P < 0.05). Meat quality detection at 49 D found all AGP groups with the higher cook loss of the breast muscle, while CT group with the higher cook loss of thigh muscle. Consequently, the overall effects of 4 AGP combinations in the whole period were not significant on growth performance. Their poor growth performance during the withdrawal period should be partly attributed to the falling off a cliff of most digestive enzyme activities from 42 to 49 D. Attention should be paid to the adverse effects of AGP supplementation on meat quality, especially cook loss.

Comparison of performance and feed digestibility of the non-antibiotic feed supplement (Novacid) and an antibiotic growth promoter in broiler chickens.

Antibiotic growth promoters have been widely used in poultry to improve overall performance. The emergence of antibiotic resistance has resulted in sanctions imposed on the use of antibiotics in poultry diets, and alternatives such as herbal extracts are being considered to improve growth performance. The aim of this study was to compare the performance and feed digestibility of the feed supplement Novacid, which contains organic acids, glucomannan, and phytochemicals, with that of the antibiotic growth promoter bacitracin methylene disalicylate (BMD) in commercial broiler chickens. Six hundred 1-d-old Ross × Ross 308 male broiler chicks were randomly and equally assigned to six treatment groups with five replicates each (20 chicks per replicate). The chicks were fed a corn-soybean meal basal diet, and divided into two groups: unchallenged and challenged with E. coli (400 mg/kg Escherichia coli inoculation). Each of these groups was divided into three study groups: untreated, treated with 0.05% Novacid, and treated with 400 mg/kg BMD. At day 42, inclusion of Novacid or BMD significantly (P < 0.05) improved the performance in the unchallenged groups relative to the control group. However, in E. coli-challenged groups, Novacid and BMD did not improve performance. Ileal digestibility of crude fat, crude protein, and gross energy were reduced in the Novacid group (P < 0.05). BMD and Novacid were equally effective in controlling ileal nutrient digestibility and feed coliform count (P < 0.05). Novacid reduced cecal E. coli and Salmonella count compared to BMD and control. Thus, a phytochemical feed supplement with organic acids and glucomannan could be an effective substitute for antibiotic growth promoters in broiler diets, but cannot replace antibiotics to counter potent infectious agents such as E. coli.

Hepatic gene body hypermethylation is a shared epigenetic signature of murine longevity.

Dietary, pharmacological and genetic interventions can extend health- and lifespan in diverse mammalian species. DNA methylation has been implicated in mediating the beneficial effects of these interventions; methylation patterns deteriorate during ageing, and this is prevented by lifespan-extending interventions. However, whether these interventions also actively shape the epigenome, and whether such epigenetic reprogramming contributes to improved health at old age, remains underexplored. We analysed published, whole-genome, BS-seq data sets from mouse liver to explore DNA methylation patterns in aged mice in response to three lifespan-extending interventions: dietary restriction (DR), reduced TOR signaling (rapamycin), and reduced growth (Ames dwarf mice). Dwarf mice show enhanced DNA hypermethylation in the body of key genes in lipid biosynthesis, cell proliferation and somatotropic signaling, which strongly correlates with the pattern of transcriptional repression. Remarkably, DR causes a similar hypermethylation in lipid biosynthesis genes, while rapamycin treatment increases methylation signatures in genes coding for growth factor and growth hormone receptors. Shared changes of DNA methylation were restricted to hypermethylated regions, and they were not merely a consequence of slowed ageing, thus suggesting an active mechanism driving their formation. By comparing the overlap in ageing-independent hypermethylated patterns between all three interventions, we identified four regions, which, independent of genetic background or gender, may serve as novel biomarkers for longevity-extending interventions. In summary, we identified gene body hypermethylation as a novel and partly conserved signature of lifespan-extending interventions in mouse, highlighting epigenetic reprogramming as a possible intervention to improve health at old age.

Microparticles Produced by Activated Platelets Carry a Potent and Functionally Active Angiogenic Signal in Subjects with Crohn's Disease.

Microparticles (MPs) are submicron vesicles shed from various cell types upon activation, stimulation, and death. Activated platelets are an important source of circulating MPs in subjects with inflammatory diseases, including Crohn's disease (CD). Angiogenesis is a hallmark of inflammation in CD and plays an active role in sustaining disease progression, while targeting angiogenesis may be an effective approach to block colitis. In this study, we analyzed the angiogenic content of the MPs produced by activated platelets in subjects with CD. We also evaluated whether the angiogenic signal carried by these MPs was functionally active, or able to induce angiogenesis. We found that, in subjects with CD, MPs produced by activated platelets contain significantly higher levels of angiogenic mRNAs, such as epidermal growth factor (EGF), platelet-derived growth factor-α (PDGFα), fibroblast growth factor (FGF-2), and angiopoietin-1 (ANGPT1), compared to MPs isolated from control subjects. They also contain significantly higher levels of prototypical angiogenic proteins, including vascular endothelial growth factor (VEGF), angiopoietin-1, endoglin, endothelin-1, pentraxin 3, platelet factor-4, plasminogen activator inhibitor-1 (PAI-1), tissue inhibitor of metalloproteinases-1 (TIMP-1), and thrombospondin 1. The protein content of these MPs is functionally active, since it has the ability to induce a robust angiogenic process in an endothelial cell/interstitial cell co-culture in vitro assay. Our results reveal a potential novel mechanism through which the angiogenic signal is delivered in subjects with CD, with potentially important clinical and therapeutic implications.

First report of Nitzschia navis-varingica in the Mediterranean Sea and growth stimulatory effects of Nitzschia navis-varingica, Chrysochromulina alifera and Heterocapsa pygmaea on different mammalian cell types.

A benthic diatom, Nitzschia navis-varingica was found for the first time in the Mediterranean Sea. Effects of this diatom species together with the haptophyte Chrysochromulina alifera and the dinoflagellate Heterocapsa pygmaea isolated from the northeastern Mediterranean Sea coast on prostate, breast cancer and fibroblast cell lines were investigated. Algal extracts did not exert any toxic effect on these cell lines and it had growth stimulatory impact on the cells without discrimination of cell type. Our results suggest potential use of these algal extracts in tissue repair and cell growth boosting additive in the diet of humans as well as animals. Moreover, these algal extracts have potential to be used as natural resource in the skin vitalizing creams of cosmetics industry and as wound healing agents in the atopic drugs.

Interactions mediated by a public good transiently increase cooperativity in growing Pseudomonas putida metapopulations.

Bacterial communities have rich social lives. A well-established interaction involves the exchange of a public good in Pseudomonas populations, where the iron-scavenging compound pyoverdine, synthesized by some cells, is shared with the rest. Pyoverdine thus mediates interactions between producers and non-producers and can constitute a public good. This interaction is often used to test game theoretical predictions on the "social dilemma" of producers. Such an approach, however, underestimates the impact of specific properties of the public good, for example consequences of its accumulation in the environment. Here, we experimentally quantify costs and benefits of pyoverdine production in a specific environment, and build a model of population dynamics that explicitly accounts for the changing significance of accumulating pyoverdine as chemical mediator of social interactions. The model predicts that, in an ensemble of growing populations (metapopulation) with different initial producer fractions (and consequently pyoverdine contents), the global producer fraction initially increases. Because the benefit of pyoverdine declines at saturating concentrations, the increase need only be transient. Confirmed by experiments on metapopulations, our results show how a changing benefit of a public good can shape social interactions in a bacterial population.

Epidermal growth factor promotes proliferation and maintains multipotency of continuous cultured adipose stem cells via activating STAT signal pathway in vitro.

This study aimed to investigate the effects of epidermal growth factor (EGF) on the proliferation and differentiation of adipose stem cells (ASC) during the repeated passaging and probe the underlying signal pathway. Results showed that the Ki67 positive rate remained at a high level, the number of ASCs in G0/G1 phase reduced significantly, but ASCs in G2/M phase and S phase increased markedly in ASCs treated with EGF when compared with ASCs without EGF treatment, indicating that EGF made more ASCs in proliferation phase. The adipogenic capability of ASCs without EGF was compromised when compared with that of ASCs after EGF treatment, although significant difference was not observed. The osteogenic and chondrogenic potencies increased significantly in ASC with EGF treatment indicating EGF could maintain differentiative capacity of ASCs. Gene Set Enrichment Analysis showed EGF upregulated the expression of molecules in the epithelial mesenchymal transition and G2/M checkpoint signal pathways. GeneMANIA database analysis indicated the network interaction between EGF and STAT. EGF receptor (EGFR) inhibitor and STAT3 inhibitor were independently used to validate the role of both pathways in these effects. After inhibition of EGFR or STAT3, the proliferation of ASCs was significantly inhibited, and Western blotting showed EGF was able to markedly increase the expression of EGFR and STAT3. These findings suggest EGF not only promotes the proliferation of ASCs and delays their senescence, but also maintains the differentiation potency of ASCs, which are related to the EGF-induced activation of STAT signal pathway.

Discrimination between Synthetically Administered and Endogenous Thiouracil Based on Monitoring of Urine, Muscle, and Thyroid Tissue: An in Vivo Study in Young and Adult Bovines.

Thiouracil (TU), synthesized for its thyroid-regulating capacities and alternatively misused in livestock for its weight-gaining effects, is acknowledged to have an endogenous origin. Discrimination between low-level abuse and endogenous occurrence is challenging and unexplored in an experimental setting. Therefore, cows (n = 16) and calves (n = 18) were subjected to a rapeseed-supplemented diet or treated with synthetic TU. Significant higher urinary TU levels were recorded after TU administration (

Chromium tolerance, oxidative stress response, morphological characteristics, and FTIR studies of phytopathogenic fungus Sclerotium rolfsii.

Sclerotium rolfsii is one of the most destructive fungal plant pathogens that can infect over 500 plants and can adapt to diverse environmental conditions. The present research work was carried out to evaluate the impact of both hexa- and trivalent chromium (Cr) on growth, morphology, enzymatic characteristics, and metal accumulation in S. rolfsii under laboratory conditions. Experiments were performed in both malt extract broth and agar growth medium amended with six different concentrations (10, 20, 40, 60, 80, and 100 ppm) of each Cr(III) and Cr(VI) ions inoculated with fungus and incubated for 6-7 days at 25 ± 3 °C. In broth medium, the total protein content was declined and activities of antioxidant enzymes were increased with an increase in metal concentrations. Lower concentrations (10 ppm) of the metal ions stimulated the growth of fungus and higher concentrations (60-100) inhibited it. The Fourier transform infrared spectroscopy (FTIR) assessment showed hydroxyl, carboxyl, and amine groups as major metal binding sites. In agar medium, tolerance index was decreased up to 0.56 at 10-80 ppm of Cr(III) and up to 0.62 at 10-60 ppm of Cr(VI). Considerable modifications were observed in hyphal and sclerotial morphology with an increase in concentration of metal ions. The current study concluded that interference of Cr with growth and physiological process of S. rolfsii could affect its infection level on its host plant. This study provides important information regarding cultivation of susceptible plant varieties in Cr-polluted soil as evidenced by pathogen growth up to 50 ppm of Cr(III) and Cr(VI) ions.

Volatile Compounds Emitted by Pseudomonas aeruginosa Stimulate Growth of the Fungal Pathogen Aspergillus fumigatus.

UNLABELLED: Chronic lung infections with opportunistic bacterial and fungal pathogens are a major cause of morbidity and mortality especially in patients with cystic fibrosis. Pseudomonas aeruginosa is the most frequently colonizing bacterium in these patients, and it is often found in association with the filamentous fungus Aspergillus fumigatus. P. aeruginosa is known to inhibit the growth of A. fumigatus in situations of direct contact, suggesting the existence of interspecies communication that may influence disease outcome. Our study shows that the lung pathogens P. aeruginosa and A. fumigatus can interact at a distance via volatile-mediated communication and expands our understanding of interspecific signaling in microbial communities. IMPORTANCE: Microbiota studies have shown that pathogens cannot be studied individually anymore and that the establishment and progression of a specific disease are due not to a single microbial species but are the result of the activity of many species living together. To date, the interaction between members of the human microbiota has been analyzed in situations of direct contact or liquid-mediated contact between organisms. This study showed unexpectedly that human opportunistic pathogens can interact at a distance after sensing volatiles emitted by another microbial species. This finding will open a new research avenue for the understanding of microbial communities.

New Analytical Tool for the Detection of Ractopamine Abuse in Goat Skeletal Muscle by Potential Gene Expression Biomarkers.

In this study, quantification of mRNA gene expression was examined as biomarkers to detect ractopamaine abuse and ractopamaine residues in cashmere goats. It was focused on the identification of potential gene expression biomarkers and describing the coreletionship between gene expression and residue level by 58 animals for 49 days. The results showed that administration periods and residue levels significantly influenced mRNA expressions of the ß2-adrenergic receptor (ß2AR), the enzymes PRKACB, ADCY3, ATP1A3, ATP2A3, PTH, and MYLK, and the immune factors IL-1ß and TNF-α. Statistical analysis like principal components analysis (PCA), hierarchical cluster analysis (HCA), and discriminant analysis (DA) showed that these genes can serve as potential biomarkers for ractopamine in skeletal muscle and that they are also suitable for describing different residue levels separately.

Enhancement of drought stress tolerance in crops by plant growth promoting rhizobacteria.

Drought is one of the major constraints on agricultural productivity worldwide and is likely to further increase. Several adaptations and mitigation strategies are required to cope with drought stress. Plant growth promoting rhizobacteria (PGPR) could play a significant role in alleviation of drought stress in plants. These beneficial microorganisms colonize the rhizosphere/endo-rhizosphere of plants and impart drought tolerance by producing exopolysaccharides (EPS), phytohormones, 1-aminocyclopropane- 1-carboxylate (ACC) deaminase, volatile compounds, inducing accumulation of osmolytes, antioxidants, upregulation or down regulation of stress responsive genes and alteration in root morphology in acquisition of drought tolerance. The term Induced Systemic Tolerance (IST) was coined for physical and chemical changes induced by microorganisms in plants which results in enhanced tolerance to drought stresses. In the present review we elaborate on the role of PGPR in helping plants to cope with drought stress.

Basic science behind the cardiovascular benefits of exercise.

Cardiorespiratory fitness is a strong predictor of cardiovascular (CV) disease and all-cause mortality, with increases in cardiorespiratory fitness associated with corresponding decreases in CV disease risk. The effects of exercise upon the myocardium and vascular system are dependent upon the frequency, intensity and duration of the exercise itself. Following a prolonged period (≥6 months) of regular intensive exercise in previously untrained individuals, resting and submaximal exercising heart rates are typically 5-20 beats lower, with an increase in stroke volume of ∼20% and enhanced myocardial contractility. Structurally, all four heart chambers increase in volume with mild increases in wall thickness, resulting in greater cardiac mass due to increased myocardial cell size. With this in mind, the present paper aims to review the basic science behind the CV benefits of exercise. Attention will be paid to understanding (1) the relationship between exercise and cardiac remodelling; (2) the cardiac cellular and molecular adaptations in response to exercise, including the examination of molecular mechanisms of physiological cardiac growth and applying these mechanisms to identify new therapeutic targets to prevent or reverse pathological remodelling and heart failure; and (3) vascular adaptations in response to exercise. Finally, this review will briefly examine how to optimise the CV benefits of exercise by considering how much and how intense exercise should be.

Growth and the Growth Hormone-Insulin Like Growth Factor 1 Axis in Children With Chronic Inflammation: Current Evidence, Gaps in Knowledge, and Future Directions.

Growth failure is frequently encountered in children with chronic inflammatory conditions like juvenile idiopathic arthritis, inflammatory bowel disease, and cystic fibrosis. Delayed puberty and attenuated pubertal growth spurt are often seen during adolescence. The underlying inflammatory state mediated by proinflammatory cytokines, prolonged use of glucocorticoid, and suboptimal nutrition contribute to growth failure and pubertal abnormalities. These factors can impair growth by their effects on the GH-IGF axis and also directly at the level of the growth plate via alterations in chondrogenesis and local growth factor signaling. Recent studies on the impact of cytokines and glucocorticoid on the growth plate further advanced our understanding of growth failure in chronic disease and provided a biological rationale of growth promotion. Targeting cytokines using biological therapy may lead to improvement of growth in some of these children, but approximately one-third continue to grow slowly. There is increasing evidence that the use of relatively high-dose recombinant human GH may lead to partial catch-up growth in chronic inflammatory conditions, although long-term follow-up data are currently limited. In this review, we comprehensively review the growth abnormalities in children with juvenile idiopathic arthritis, inflammatory bowel disease, and cystic fibrosis, systemic abnormalities of the GH-IGF axis, and growth plate perturbations. We also systematically reviewed all the current published studies of recombinant human GH in these conditions and discussed the role of recombinant human IGF-1.

Ractopamine Residues in Beef Cattle Hair During and After Treatment.

The objective of the present study was to assess the accumulation of ractopamine (RAC) residues in hair of Chinese Simmental beef cattle following exposure to two doses of RAC for 28 days. Six male cattle were orally administered with RAC hydrochloride at a dose of 0.67 mg/kg body weight/day (low-dose group, n = 3) and 2.01 mg/kg body weight/day (high-dose group, n = 3). The results suggested that RAC was obviously accumulated in hair, with a concentration of 5.57 ± 0.66 ng/g (white hair) and 13.67 ± 2.73 ng/g (red hair) in the low-dose group on Day 1 of treatment, respectively. In red hair, the peak concentrations of RAC were 5619.38 ± 2156.84 ng/g (low-dose group) and 6908.3 ± 1177.62 ng/g (high-dose group) on Day 14 of treatment, and then decreased slowly. In white hair, the highest concentrations of RAC were 3387.38 ± 1620.87 ng/g (low-dose group) on Day 14 of withdraw and 9621.72 ± 1497.65 ng/g (high-dose group) on Day 28 of treatment. The concentration of RAC in old hair was higher than that in new hair. No significant differences in RAC concentrations were obtained among dosage, hair color and old versus new hair (P > 0.05). The results indicated that ractopamine is significantly accumulated in red and white hair of Chinese Simmental beef cattle, which can be used as a matrix to assess the presence of RAC residues.