The Effect of Probiotics Supplementation on Helicobacter pylori Eradication Rates and Side Effects during Eradication Therapy: A Meta-Analysis

Background

Previous meta-analyses reported that probiotics improve the effectiveness of Helicobacter pylori (H. pylori) eradication during antibiotic therapy, while results regarding a possible reduction of side effects remained inconclusive. Moreover, the effectiveness of different strains of probiotics has not been studied so far. It is further conceivable that probiotics will produce additional effects only if antibiotics are relatively ineffective.

Methods

This meta-analysis includes eligible randomized controlled trials examining effects of probiotics supplementation on eradication rates (ER) and side effects, published up to May 2014. Sub-group analysis was performed to compare different probiotic strains and antibiotic therapies with different effectiveness in controls (ER <80% vs.>80%). Publication bias was assessed with funnel plots and Harbord''s test. The quality of the trials was assessed with the Cochrane risk of bias tool.

Results

Thirty-three RCTs involving a total of 4459 patients met the inclusion criteria in case of eradication rates of which 20 assessed total side effects in addition. Overall, the pooled eradication rate in probiotics supplementation groups was significantly higher than in controls (ITT analysis: RR 1.122, 95% CI 1.086–1.159, PP analysis: RR 1.114, 95% CI 1.070–1.159). Sub group-analysis could, however, confirm this finding only for four individual strains (Lactobacillus acidophilus, Lactobacillus casei DN-114001, Lactobacillus gasseri, and Bifidobacterium infantis 2036) and for relatively ineffective antibiotic therapies. There was a significant difference between groups in the overall incidence of side effects (RR 0.735, 95% CI 0.598–0.902). This result was, however, only confirmed for non-blinded trials.

Conclusions

The pooled data suggest that supplementation with specific strains of probiotics compared with eradication therapy may be considered an option for increasing eradication rates, particularly when antibiotic therapies are relatively ineffective. The impact on side effects remains unclear and more high quality trials on specific probiotic strains and side effects are thus needed.     

Bone Response to Fluoride Exposure Is Influenced by Genetics

Genetic factors influence the effects of fluoride (F) on amelogenesis and bone homeostasis but the underlying molecular mechanisms remain undefined. A label-free proteomics approach was employed to identify and evaluate changes in bone protein expression in two mouse strains having different susceptibilities to develop dental fluorosis and to alter bone quality. In vivo bone formation and histomorphometry after F intake were also evaluated and related to the proteome. Resistant 129P3/J and susceptible A/J mice were assigned to three groups given low-F food and water containing 0, 10 or 50 ppmF for 8 weeks. Plasma was evaluated for alkaline phosphatase activity. Femurs, tibiae and lumbar vertebrae were evaluated using micro-CT analysis and mineral apposition rate (MAR) was measured in cortical bone. For quantitative proteomic analysis, bone proteins were extracted and analyzed using liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS), followed by label-free semi-quantitative differential expression analysis. Alterations in several bone proteins were found among the F treatment groups within each mouse strain and between the strains for each F treatment group (ratio ≥1.5 or ≤0.5; p<0.05). Although F treatment had no significant effects on BMD or bone histomorphometry in either strain, MAR was higher in the 50 ppmF 129P3/J mice than in the 50 ppmF A/J mice treated with 50 ppmF showing that F increased bone formation in a strain-specific manner. Also, F exposure was associated with dose-specific and strain-specific alterations in expression of proteins involved in osteogenesis and osteoclastogenesis. In conclusion, our findings confirm a genetic influence in bone response to F exposure and point to several proteins that may act as targets for the differential F responses in this tissue.     

Comparative In Vitro Study on Magnetic Iron Oxide Nanoparticles for MRI Tracking of Adipose Tissue-Derived Progenitor Cells

Magnetic resonance imaging (MRI) using measurement of the transverse relaxation time (R2*) is to be considered as a promising approach for cell tracking experiments to evaluate the fate of transplanted progenitor cells and develop successful cell therapies for tissue engineering. While the relationship between core composition of nanoparticles and their MRI properties is well studied, little is known about possible effects on progenitor cells. This in vitro study aims at comparing two magnetic iron oxide nanoparticle types, single vs. multi-core nanoparticles, regarding their physico-chemical characteristics, effects on cellular behavior of adipose tissue-derived stem cells (ASC) like differentiation and proliferation as well as their detection and quantification by means of MRI. Quantification of both nanoparticle types revealed a linear correlation between labeling concentration and R2* values. However, according to core composition, different levels of labeling concentrations were needed to achieve comparable R2* values. Cell viability was not altered for all labeling concentrations, whereas the proliferation rate increased with increasing labeling concentrations. Likewise, deposition of lipid droplets as well as matrix calcification revealed to be highly dose-dependent particularly regarding multi-core nanoparticle-labeled cells. Synthesis of cartilage matrix proteins and mRNA expression of collagen type II was also highly dependent on nanoparticle labeling. In general, the differentiation potential was decreased with increasing labeling concentrations. This in vitro study provides the proof of principle for further in vivo tracking experiments of progenitor cells using nanoparticles with different core compositions but also provides striking evidence that combined testing of biological and MRI properties is advisable as improved MRI properties of multi-core nanoparticles may result in altered cell functions.     

Fibrillin-1 and alpha8 integrin are co-expressed in the glomerulus and interact to convey adhesion of mesangial cells

Fibrillin-1 is a microfibrillar extracellular matrix protein that was described to be a ligand for α8 integrin. α8 integrin is a matrix receptor specifically expressed in mesangial and smooth muscle cells of the kidney. In previous studies we detected glomerular expression of fibrillin-1. Moreover, fibrillin-1 promoted adhesion, migration, and proliferation of mesangial cells. We hypothesized that fibrillin-1 and α8 integrin might interact in the glomerulus, and thus, regulate mesangial cell properties. Our studies showed that fibrillin-1 and α8 integrin colocalize in the glomerular mesangium. Induction of experimental glomerulonephritis led to an increase of both fibrillin-1 and α8 integrin expression. In vitro studies revealed that mesangial cells deficient for α8 integrin adhere weaker to fibrillin-1 and migrate more easily on fibrillin-1 than wild-type mesangial cells. Baseline proliferation on fibrillin-1 is higher in α8 integrin-deficient mesangial cells, but the induction of proliferation is not different in α8 integrin-deficient and wild-type mesangial cells. We conclude that fibrillin-1 and α8 integrin interact, and thus, regulate mesangial cell adhesion and migration. The concomitant induction of both fibrillin-1 and α8 integrin in a self-limited model of glomerular injury points to a protective role of the interaction of fibrillin-1 with α8 integrin in the glomerulus resulting in reduced damage of the glomerular tuft as a consequence of firm adhesion of mesangial cells.     

In vivo impact of Dlx3 conditional inactivation in neural crest‐derived craniofacial bones

Mutations in DLX3 in humans lead to defects in craniofacial and appendicular bones, yet the in vivo activities related to Dlx3 function during normal skeletal development have not been fully elucidated. Here we used a conditional knockout approach to analyze the effects of neural crest deletion of Dlx3 on craniofacial bones development. At birth, mutant mice exhibit a normal overall positioning of the skull bones, but a change in the shape of the calvaria was observed. Molecular analysis of the genes affected in the frontal bones and mandibles from these mice identified several bone markers known to affect bone development, with a strong prediction for increased bone formation and mineralization in vivo. Interestingly, while a subset of these genes were similarly affected in frontal bones and mandibles (Sost, Mepe, Bglap, Alp, Ibsp, Agt), several genes, including Lect1 and Calca, were specifically affected in frontal bones. Consistent with these molecular alterations, cells isolated from the frontal bone of mutant mice exhibited increased differentiation and mineralization capacities ex vivo, supporting cell autonomous defects in neural crest cells. However, adult mutant animals exhibited decreased bone mineral density in both mandibles and calvaria, as well as a significant increase in bone porosity. Together, these observations suggest that mature osteoblasts in the adult respond to signals that regulate adult bone mass and remodeling. This study provides new downstream targets for Dlx3 in craniofacial bone, and gives additional evidence of the complex regulation of bone formation and homeostasis in the adult skeleton. J. Cell. Physiol. 228: 654–664, 2013. © 2012 Wiley Periodicals, Inc.     

New karyotype for Mesomys stimulax (Rodentia,Echimyidae) from the Brazilian Amazon: A case for species complex?

Mesomys Wagner, 1845 (Rodentia, Echimyidae, Eumysopinae) currently has four recognized species, three of which occur in Brazil: Mesomys hispidus (probably a species complex), M. occultus, and M. stimulax. Mesomys leniceps is found in montane forests of northern Peru. Mesomys stimulax, the focus of the present study, has a distribution that is restricted to the central and eastern Amazonia south of the Amazon River, extending from the left bank of the Tapajós River to the right bank of the Tocantins River, and south to the southeast portion of Pará State. The genus presents karyotypes with diploid number 2n = 60 and Fundamental Number (FN) = 116 for M. hispidus and M. stimulax, and 2n = 42, FN = 54 for M. occultus. We studied the karyotype of a female specimen of M. stimulax collected from the Tapirapé‐Aquiri National Forest, Marabá, Pará, Brazil, in the Xingu/Tocantins interfluvium. The obtained karyotype (2n = 60 and FN = 110) differs from that described in the literature for both M. stimulax and M. hispidus by exhibiting more biarmed chromosomes, probably due to pericentric inversions and/or centromeric repositioning, and exhibiting differences in the amount and distribution of constitutive heterochromatin (CH). These results suggest that, similar to what has already been proposed for M. hispidus, M. stimulax may represent a species complex and/or cryptic species. The mechanisms of chromosomal diversification in Mesomys and the biogeographic implications are discussed reinforcing the need for broad systematic review for Mesomys.     

NeutrobodyPlex—monitoring SARS‐CoV‐2 neutralizing immune responses using nanobodies

In light of the COVID‐19 pandemic, there is an ongoing need for diagnostic tools to monitor the immune status of large patient cohorts and the effectiveness of vaccination campaigns. Here, we present 11 unique nanobodies (Nbs) specific for the SARS‐CoV‐2 spike receptor‐binding domain (RBD), of which 8 Nbs potently inhibit the interaction of RBD with angiotensin‐converting enzyme 2 (ACE2) as the major viral docking site. Following detailed epitope mapping and structural analysis, we select two inhibitory Nbs, one of which binds an epitope inside and one of which binds an epitope outside the RBD:ACE2 interface. Based on these, we generate a biparatopic nanobody (bipNb) with viral neutralization efficacy in the picomolar range. Using bipNb as a surrogate, we establish a competitive multiplex binding assay (“NeutrobodyPlex”) for detailed analysis of the presence and performance of neutralizing RBD‐binding antibodies in serum of convalescent or vaccinated patients. We demonstrate that NeutrobodyPlex enables high‐throughput screening and detailed analysis of neutralizing immune responses in infected or vaccinated individuals, to monitor immune status or to guide vaccine design.     

Potential sexual transmission of environmental microbes in a traumatically inseminating insect

Abstract.  1. Very little attention has been paid to the importance of environmental microbes and how they gain access to potential hosts during host wounding or sexual interactions. Male members of the family Cimicidae (including the haematophagous human pest, the bed bug, Cimex lectularius ) show traumatic insemination: in order to transfer sperm the male punctures the female's cuticle using a needle-like intromittent organ. The microbes from the local environment that gain entry into females during mating have previously been shown to be an important source of mortality. This study aimed to identify these microbes and their natural environmental substrates.
2. Nine different microbe taxa from the surface of the cuticle were identified, five of them (two Penicillium spp., Stenotrophomonas , Enterobacter , Bacillus ) were found in the local environment as well as on the intromittent organ of male bed bugs: these are strong candidates for the causal agents of mating-induced female mortality. Local differences in the microbial communities and their hosts' response to them are discussed as a source of reproductive isolation.
3. Four microbe genera ( Scopulariopsis , Staphylococcus , Arthrobacter , Micrococcus ) were found exclusively on blood agar. One of them, and four grown on regular agar, are classified as human pathogens. However, because no microbes were isolated from the piercing and sucking mouthparts the epidemiological significance of bed bugs carrying externally attached microbes is probably low.     

Using the dual isotope method to assess cecal amino acid absorption of goat whey protein in rats,a pilot study

Measurement of ileal amino acids (AA) bioavailability is recommended to evaluate protein quality. A dual isotope tracer method, based on plasma isotopic enrichment ratios, has been proposed to determine true digestibility in humans. In a pilot study, we aimed to evaluate whether this method could be implemented in rats to determine AA bioavailability based on isotopic enrichment ratios measured in cecal digesta or plasma samples. Goat milk proteins were intrinsically labeled with ¹⁵N and ²H. Wistar rats were fed a meal containing the doubly labeled goat whey proteins and a tracer dose of ¹³C-spirulina. Blood samples were collected 0, 1 h and 3 h after meal ingestion from the tail vein. The rats were euthanized 4 h (n?=?6) or 6 h (n?=?6) after meal to collect plasma and intestinal contents. True orocecal protein digestibility and AA bioavailability were assessed by means of ¹⁵N and ²H enrichment in cecum content and compared with absorption indexes determined at the plasma or cecum level using isotopic ratios. Plasma kinetics of isotopic enrichment could not be completed due to the limited quantity of plasma obtained with sequential blood collection. However, the absorption indexes determined from cecal ¹⁵N or ²H/¹³C ratios gave coherent values with true orocecal AA bioavailability. This dual isotope approach with measurements of isotopic ratios in digestive content could be an interesting strategy to determine true AA bioavailability in ileal digesta of rats.