Irritable Bowel Syndrome and Neurological Deficiencies: Is There A Relationship? The Possible Relevance of the Oxidative Stress Status.

Background: Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders, exhibiting complex and controversial pathological features. Both oxidative stress and inflammation-related reactive oxygen species production may be involved in IBS pathological development. Thus, we focused on several aspects regarding the causes of oxidative stress occurrence in IBS. Additionally, in the molecular context of oxidative changes, we tried to discuss these possible neurological implications in IBS. Methods: The literature search included the main available databases (e.g., ScienceDirect, Pubmed/Medline, Embase, and Google Scholar). Articles in the English language were taken into consideration. Our screening was conducted based on several words such as "irritable bowel syndrome", "gut brain axis", "oxidative stress", "neuroendocrine", and combinations. Results: While no consistent evidence suggests clear pathway mechanisms, it seems that the inflammatory response may also be relevant in IBS. The mild implication of oxidative stress in IBS has been described through clinical studies and some animal models, revealing changes in the main markers such as antioxidant status and peroxidation markers. Moreover, it seems that the neurological structures involved in the brain-gut axis may be affected in IBS rather than the local gut tissue and functionality. Due to a gut-brain axis bidirectional communication error, a correlation between neurological impairment, emotional over-responsiveness, mild inflammatory patterns, and oxidative stress can be suggested. Conclusions: Therefore, there is a possible correlation between neurological impairment, emotional over-responsiveness, mild inflammatory patterns, and oxidative stress that are not followed by tissue destruction in IBS patients. Moreover, it is not yet clear whether oxidative stress, inflammation, or neurological impairments are key determinants or in which way these three interact in IBS pathology. However, the conditions in which oxidative imbalances occur may be an interesting research lead in order to find possible explanations for IBS development.

Irritable Bowel Syndrome between Molecular Approach and Clinical Expertise-Searching for Gap Fillers in the Oxidative Stress Way of Thinking.

Irritable bowel syndrome (IBS) remains to date an intriguing functional gastrointestinal disorder. Recent studies described a multitude of exogenous factors that work together in IBS, gradually impairing intestinal lining cellular metabolism, including oxidative status balance, with or without a genetic background. Although the current biomarkers support the differentiation between IBS subtypes and other functional gastrointestinal disorder, they are mostly non-specific, referring to clinical, biochemical, and inflammatory imbalances. Since IBS could be also the result of deficient signaling pathways involving both gastrointestinal secretion and neuro-vegetative stimulation, IBS makes no exception from the oxidative hypothesis in the pathological mechanisms. Regarding the oxidative stress implication in IBS, the previous research efforts showed controversial results, with some animal models and patient studies reporting clear oxidative imbalance both on systemic and local levels, but still with no concrete evidence to point to a direct correlation between oxidative stress and IBS. Additionally, it seems that a major role could be also attributed to gut microbiota and their ability to shape our bodies and behaviors. Moreover, the genetic features study in IBS patients showed that several genetic similarities point to a possible correlation of IBS with affective spectrum disorders. Thus, we focus here the discussion on the assumption that IBS could in fact be more likely a stress-related disorder rather than a gastrointestinal one.

Molecular diversity and phylogeny of indigenous Rhizobium leguminosarum strains associated with Trifolium repens plants in Romania.

The symbiotic nitrogen fixing legumes play an essential role in sustainable agriculture. White clover (Trifolium repens L.) is one of the most valuable perennial legumes in pastures and meadows of temperate regions. Despite its great agriculture and economic importance, there is no detailed available information on phylogenetic assignation and characterization of rhizobia associated with native white clover plants in South-Eastern Europe. In the present work, the diversity of indigenous white clover rhizobia originating in 11 different natural ecosystems in North-Eastern Romania were assessed by a polyphasic approach. Initial grouping showed that, 73 rhizobial isolates, representing seven distinct phenons were distributed into 12 genotypes, indicating a wide phenotypic and genotypic diversity among the isolates. To clarify their phylogeny, 44 representative strains were used in sequence analysis of 16S rRNA gene and IGS fragments, three housekeeping genes (atpD, glnII and recA) and two symbiosis-related genes (nodA and nifH). Multilocus sequence analysis (MLSA) phylogeny based on concatenated housekeeping genes delineated the clover isolates into five putative genospecies. Despite their diverse chromosomal backgrounds, test strains shared highly similar symbiotic genes closely related to Rhizobium leguminosarum biovar trifolii. Phylogenies inferred from housekeeping genes were incongruent with those of symbiotic genes, probably due to occurrence of lateral transfer events among native strains. This is the first polyphasic taxonomic study to report on the MLSA-based phylogenetic diversity of indigenous rhizobia nodulating white clover plants grown in various soil types in South-Eastern Europe. Our results provide valuable taxonomic data on native clover rhizobia and may increase the pool of genetic material to be used as biofertilizers.

RAPD-inferred genetic variability of some indigenous Rhizobium leguminosarum isolates from red clover (Trifolium pratense L.) nodules.

The application of commercial rhizobial inoculants to legume crops is proving to be an alternative to synthetic fertilizer use. The challenge for sustainable agriculture resides in the compatibility between crop, inoculants and environmental conditions. The evaluation of symbiotic efficiency and genetic diversity of indigenous rhizobial strains could lead to the development of better inoculants and increased crop production. The genetic variability of 32 wild indigenous rhizobial isolates was assessed by RAPD (Random Amplified Polymorphic DNA). The strains were isolated from red clover (Trifolium pratense L.) nodules from two distinct geographical regions of Northern and Eastern Romania. Three decamer primers were used to resolve the phylogenetic relationships between the investigated isolates. Cluster analysis revealed a high diversity; most strains clustered together based on their geographical location.

Parkinson's Disease-Induced Zebrafish Models: Focussing on Oxidative Stress Implications and Sleep Processes.

The complex yet not fully understood pathophysiology of Parkinson's disease includes an important molecular component consisting of oxidative status changes, thus leading to oxidative stress occurrence. While no particular evidence has been reported that describes the relationship between oxidative stress and the molecular mechanisms behind Parkinson's disease development, animal model studies has shown that oxidative stress induction could modulate Parkinson's disease symptomatology. Despite the inability to perfectly replicate human disease in animals and despite that Parkinson's disease has not been reported in any animal species, animal modeling is one of the most important tools in understanding the complex mechanisms of human disorders. In this way, this study is aimed at detailing this particular relationship and describing the molecular mechanisms underlying Parkinson's disease in animal models, focusing on the potential advantages and disadvantages of zebrafish in this context. The information relevant to this topic was gathered using major scientific database research (PubMed, Google Scholar, Web of Science, and Scopus) based on related keywords and inclusion criteria. Thus, it was observed that oxidative stress possesses an important role in Parkinson's disease as shown by numerous animal model studies, many of which are based on rodent experimental models. However, an emerging impact of the zebrafish model was observed in the research of Parkinson's disease pathological mechanisms with regard to disease development factors and the cause-effect relationship between oxidative stress and comorbidities (such as depression, hyposmia, fatigue, sleep disturbances, and cognitive deficits) and also with regard to the pharmacological potential of antioxidant molecules in Parkinson's disease treatment.

Preliminary Study on the Tears Oxidative Stress Status and Sleep Disturbances in Irritable Bowel Syndrome Patients.

According to the latest gastrointestinal disorders diagnostic criteria (ROME IV), the irritable bowel syndrome (IBS) is mainly characterized by the presence of abdominal pain and changes in intestinal transit. However, both sleep impairments and oxidative status changes (in patients' sera, mucosal level, and other body fluids) were reported IBS. Thus, in this study, we aimed to evaluate several aspects regarding the oxidative stress status in patients' tears as well as sleep disturbances by comparison with the intensity of IBS symptoms, as assessed by the visual analogue scale for irritable bowel syndrome (VAS-IBS). Ten IBS patients and fourteen healthy sex- and age-matched volunteers were recruited from the Oftaprof Ophthalmological Clinic (Iași, Romania). Visual analogue scale for irritable bowel syndrome and the Pittsburgh Sleep Quality Index (PSQI) questionnaires were administered to all the patients. Tear samples were collected using the Schirmer test procedure and were subjected to biochemical analysis-superoxide dismutase and glutathione peroxidase activities, malondialdehyde, and total soluble proteins levels were determined. Standard statistical analysis was applied. We found significant differences in oxidative stress marker dynamics in IBS patients as compared to healthy age- and sex-matched controls: increased superoxide dismutase activity (p = 0.02), increased malondialdehyde (p = 0.007), and total soluble proteins levels (p = 0.019). We found no significant differences in tear glutathione peroxidase activity in IBS patients as compared to healthy age- and sex-matched controls (p = 0.55). Furthermore, we observed that the oxidative stress tear markers are correlated with gastrointestinal symptoms severity (as evaluated by VAS-IBS) but not correlated to the sleep quality index and items (as evaluated by PSQI), with significant differences according to patient sex and IBS subtype stratification. In this way, this study brings additional evidence of the oxidative stress role in IBS pathology alongside the evaluation of tear fluid molecular dynamics in IBS for the first time in our best knowledge.

Effects of air transient spark discharge and helium plasma jet on water, bacteria, cells, and biomolecules.

Atmospheric pressure DC-driven self-pulsing transient spark (TS) discharge operated in air and pulse-driven dielectric barrier discharge plasma jet (PJ) operated in helium in contact with water solutions were used for inducing chemical effects in water solutions, and the treatment of bacteria (Escherichia coli), mammalian cells (Vero line normal cells, HeLa line cancerous cells), deoxyribonucleic acid (dsDNA), and protein (bovine serum albumin). Two different methods of water solution supply were used in the TS: water electrode system and water spray system. The effects of both TS systems and the PJ were compared, as well as a direct exposure of the solution to the discharge with an indirect exposure to the discharge activated gas flow. The chemical analysis of water solutions was performed by using colorimetric methods of UV-VIS absorption spectrophotometry. The bactericidal effects of the discharges on bacteria were evaluated by standard microbiological plate count method. Viability, apoptosis and cell cycle were assessed in normal and cancerous cells. Viability of cells was evaluated by trypan blue exclusion test, apoptosis by Annexin V-FITC/propidium iodide assay, and cell cycle progression by propidium iodide/RNase test. The effect of the discharges on deoxyribonucleic acid and protein were evaluated by fluorescence and UV absorption spectroscopy. The results of bacterial and mammalian cell viability, apoptosis, and cell cycle clearly show that cold plasma can inactivate bacteria and selectively target cancerous cells, which is very important for possible future development of new plasma therapeutic strategies in biomedicine. The authors found that all investigated bio-effects were stronger with the air TS discharge than with the He PJ, even in indirect exposure.

Intranigral lipopolysaccharide induced anxiety and depression by altered BDNF mRNA expression in rat hippocampus.

It is known that lipopolysaccharide (LPS) treatment induces neuroinflammation and memory deterioration. One of the mechanisms may be the interference with brain-derived neurotrophic factor (BDNF) gene expression and function. Lipopolysaccharide (3 µg/kg and 10 µg/kg) was unilaterally injected into the substantia nigra of adult male Wistar rats. Pergolide-induced rotational behavior test was employed to validate unilateral damage to the dopamine nigrostriatal neurons. Anxiety-depression-like behaviors were studied by means of elevated plus-maze task and forced swimming test, as animal models of anxiety and depression. Rats given LPS exhibited the following: decrease of the percentage of the time spent and the number of entries in the open arm within elevated plus-maze test and decrease of swimming and increase of immobility times within forced swimming test. In addition, these behaviors are associated with decreased BDNF mRNA expression in rat hippocampus. Taken together, these data indicate that intranigral LPS infusion influences the induction of BDNF mRNA expression within hippocampus which contributes to observed behavioral responses in rats, with relevance for Parkinson's disease conditions.

Evidence of hepatitis E infection in swine and humans in the East Region of Romania.

OBJECTIVE: Swine hepatitis E virus (HEV) is considered to be a new zoonotic agent due to its close genomic resemblance to the human HEV. The aim of this study was to determine human HEV seroprevalence in eastern Romania and to characterize circulating swine HEV sequences. METHODS: Serological investigations of human serum samples were done using a commercial ELISA kit (MP Biomedicals). Swine faecal samples were tested to detect the HEV ORF2 sequence by nested reverse transcription PCR. RESULTS: One hundred and forty-eight human serum samples were tested for anti-HEV IgG of which 22 were found to be positive. Fresh swine faeces (pools) were collected from five farms in eastern Romania. Six out of 19 pooled samples were positive for HEV RNA. Phylogenetic analysis based on alignment of the ORF2 sequence indicated that the Romanian swine HEV isolates belonged to genotype 3. CONCLUSIONS: This is the first study showing HEV to be present in Romanian pig herds and that the human population is exposed.

Tissue- and developmental stage-specific activation of alpha 5 and alpha 6(IV) collagen expression in the upper gastrointestinal tract of transgenic mice.

Little is known about mechanisms regulating gene expression for the alpha chains of basement membrane type IV collagen, arranged head-to-head in transcription units COL4A1-COL4A2, COL4A3-COL4A4, and COL4A5-COL4A6, and implicated broadly in genetic diseases. To investigate these mechanisms, we generated transgenic mouse lines bearing 5'-flanking sequences of COL4A5 and COL4A6, cloned upstream of a lacZ reporter gene. A 3.8-kb fragment upstream of COL4A6 directs reporter gene expression in the esophagus, stomach, and duodenum, whereas a 13.8-kb fragment directs expression in the esophagus only. A 10.6-kb fragment upstream of COL4A5 directs expression in the esophagus. Coupled with evidence of long-range conservation between human and mouse non-coding sequences, described herein, our findings provide the first indication that highly specialized patterns characteristic of COL4A5-COL4A6 expression in vivo arise from effects of distributed cis-acting regulatory elements on a bidirectional proximal promoter, itself transcriptionally competent.

An unusual case of bronchiolitis obliterans organizing pneumonia concomitant with bronchioloalveolar carcinoma.

Although bronchiolitis obliterans organizing pneumonia (BOOP) has been associated with a variety of underlying disorders, the majority of cases of BOOP are idiopathic. We present the case of a 61-year-old patient with fever, dry cough, bilateral patchy consolidation and high erythrocyte sedimentation rate. Open lung biopsy shows coexistence of BOOP and bronchioloalveolar carcinoma. It is interesting that both diseases are predominantly air space diseases and present similar radiologic features making the diagnosis and follow-up of treatment more difficult.