Nanovesicular Mediation of the Gut-Brain Axis by Probiotics: Insights into Irritable Bowel Syndrome.

BACKGROUND: Dysbiosis, influenced by poor diet or stress, is associated with various systemic diseases. Probiotic supplements are recognized for stabilizing gut microbiota and alleviating gastrointestinal issues, like irritable bowel syndrome (IBS). This study focused on the tryptophan pathways, which are important for the regulation of serotonin levels, and on host physiology and behavior regulation. METHODS: Nanovesicles were isolated from the plasma of subjects with chronic diarrhea, both before and after 60 days of consuming a probiotic mix (Acronelle®, Bromatech S.r.l., Milan, Italy). These nanovesicles were assessed for the presence of Tryptophan 2,3-dioxygenase 2 (TDO 2). Furthermore, the probiotics mix, in combination with H2O2, was used to treat HT29 cells to explore its cytoprotective and anti-stress effect. RESULTS: In vivo, levels of TDO 2 in nanovesicles were enhanced in the blood after probiotic treatment, suggesting a role in the gut-brain axis. In the in vitro model, a typical H2O2-induced stress effect occurred, which the probiotics mix was able to recover, showing a cytoprotective effect. The probiotics mix treatment significantly reduced the heat shock protein 60 kDa levels and was able to preserve intestinal integrity and barrier function by restoring the expression and redistribution of tight junction proteins. Moreover, the probiotics mix increased the expression of TDO 2 and serotonin receptors. CONCLUSIONS: This study provides evidence for the gut-brain axis mediation by nanovesicles, influencing central nervous system function.

Inflammatory Bowel Diseases: An Updated Overview on the Heat Shock Protein Involvement.

Inflammatory bowel diseases (IBDs) represent chronic idiopathic disorders, including Crohn's disease (CD) and ulcerative colitis (UC), in which one of the trigger factors is represented by aberrant immune interactions between the intestinal epithelium and the intestinal microbiota. The involvement of heat shock proteins (HSPs) as etiological and pathogenetic factors is becoming of increasing interest. HSPs were found to be differentially expressed in the intestinal tissues and sera of patients with CD and UC. It has been shown that HSPs can play a dual role in the disease, depending on the stage of progression. They can support the inflammatory and fibrosis process, but they can also act as protective factors during disease progression or before the onset of one of the worst complications of IBD, colorectal cancer. Furthermore, HSPs are able to mediate the interaction between the intestinal microbiota and intestinal epithelial cells. In this work, we discuss the involvement of HSPs in IBD considering their genetic, epigenetic, immune and molecular roles, referring to the most recent works present in the literature. With our review, we want to shed light on the importance of further exploring the role of HSPs, or even better, the role of the molecular chaperone system (CS), in IBD: various molecules of the CS including HSPs may have diagnostic, prognostic and therapeutic potential, promoting the creation of new drugs that could overcome the side-effects of the therapies currently used.

From Dysbiosis to Neurodegenerative Diseases through Different Communication Pathways: An Overview.

The microbiome research field has rapidly evolved over the last few decades, becoming a major topic of scientific and public interest. The gut microbiota (GM) is the microbial population living in the gut. The GM has many functions, such as maintaining gut homeostasis and host health, providing defense against enteric pathogens, and involvement in immune system development. Several studies have shown that GM is implicated in dysbiosis and is presumed to contribute to neurodegeneration. This review focuses mainly on describing the connection between the intestinal microbiome alterations (dysbiosis) and the onset of neurodegenerative diseases to explore the mechanisms that link the GM to nervous system health, such as the gut-brain axis, as well as the mitochondrial, the adaptive humoral immunity, and the microvesicular pathways. The gut-brain communication depends on a continuous bidirectional flow of molecular signals exchanged through the neural and the systemic circulation. These pathways represent a possible new therapeutic target against neuroinflammation and neurodegeneration. Progress in this context is desperately needed, considering the severity of most neurodegenerative diseases and the current lack of effective treatments.

Inflammatory bowel disease and infertility: analysis of literature and future perspectives.

BACKGROUND: inflammatory bowel diseases (IBD) are chronic disorders that affect the gastrointestinal tract but which also present extraintestinal manifestations. One of the problems related to IBD is the presence of both female and male infertility. AIM: determine the correlation between IBD and male and female infertility by analyzing the literature. MATERIAL AND METHODS: Studies carried out in the last twenty years have been selected through the pubmed search engine. Only studies were selected that in their conclusions showed a real correlation between IBD and infertility. RESULTS: the first cause of infertility in both sexes is related to the surgical interventions that patients have to face during the course of the disease, but there are also psychological causes or causes related to the use of drugs used for therapy. CONCLUSIONS: further studies are needed to understand what are the real mechanisms underlying infertility in subjects suffering from IBD.

Extracellular vesicles derived from gut microbiota in inflammatory bowel disease and colorectal cancer.

The human gut microbiome encompasses inter alia, the myriad bacterial species that create the optimal host-microorganism balance essential for normal metabolic and immune function. Various lines of evidence suggest that dysregulation of the microbiota-host interaction is linked to pathologies such as inflammatory bowel disease (IBD) and colorectal cancer (CRC). Extracellular vesicles (EVs), found in virtually all body fluids and produced by both eukaryotic cells and bacteria are involved in cell-cell communication and crosstalk mechanisms, such as the immune response, barrier function and intestinal flora. This review highlights advancements in knowledge of the functional role that EVs may have in IBD and CRC, and discusses the possible use of EVs derived from intestinal microbiota in therapeutic strategies for treating these conditions.

CT-guided transthoracic needle biopsy: advantages in histopathological and molecular tests.

Aim: The present study aimed to demonstrate that computed tomography-guided transthoracic needle biopsy (TTNB) is a safe procedure that gives a more accurate pre-operative tissue diagnosis for peripheral lung nodules than transthoracic needle aspiration, obtaining suitable samples for molecular test in lung adenocarcinomas. Patients & methods: Between December 2016 and March 2018 at Thoracic Surgery Department of the University of Palermo - Policlinico Paolo Giaccone hospital, TTNB was performed in 42 patients with computed tomography-detected peripheral lung nodules >10 mm, using 16-18-Gauge Tru-Cut needles. Results: With TTNB, we have estimated an accuracy for tissue diagnosis of 97.6%. At the molecular test, EGFR overexpression and ALK mutation resulted positive for 12/23 patients with lung adenocarcinoma. Conclusion: TTNB has showed a low rate of complications and it is adoptable as standard diagnostic procedure for peripheral lung nodules.

Probiotics Can Cure Oral Aphthous-Like Ulcers in Inflammatory Bowel Disease Patients: A Review of the Literature and a Working Hypothesis.

Dysbiosis has been associated with the onset of several chronic autoimmune or inflammatory pathologies (e.g., inflammatory bowel diseases-IBD), because of its primary role in the establishment of a chronic inflammatory process leading to tissue damage. Inflammatory bowel diseases can even involve areas far away from the gut, such as the extraintestinal manifestations involving the oral cavity with the onset of aphthous-like ulcers (ALU). Studies carried out on animal models have shown that intestinal dysbiosis may be related to the development of autoimmune diseases, even if the mechanisms involved are not yet well known. The aim of this paper is to verify the hypothesis that in inflammatory bowel diseases patients, aphthous-like ulcers are the result of the concomitance of intestinal dysbiosis and other events, e.g., the microtraumas, occurring in the oral mucosa, and that ex adiuvantibus therapy with probiotics can be employed to modify the natural course of the aphthous-like ulcers.

Hsp60 as a Novel Target in IBD Management: A Prospect.

Inflammatory bowel disease (IBD) encompasses various pathological conditions similar but distinct that share a multifactorial etiology, including involvement of the intestinal barrier function, the immune system, and intestinal microorganisms. Hsp60 is a chaperonin component of the chaperoning system, present in all cells and tissues, including the intestine. It plays important roles in cell physiology outside and inside mitochondria, its canonical place of residence. However, Hsp60 can also be pathogenic in many conditions, the Hsp60 chaperonopathies, possibly including IBD. The various clinico-pathological types of IBD have a complicated mix of causative factors, among which Hsp60 can be considered a putatively important driver of events and could play an etiopathogenic role. This possibility is discussed in this review. We also indicate that Hsp60 can be a biomarker useful in disease diagnosing and monitoring and, if found active in pathogenesis, should become a target for developing new therapies. The latter are particularly needed to alleviate patient suffering and to prevent complications, including colon cancer.

Permanence of Modifications in Oral Microcirculation in Ex-Smokers.

BACKGROUND The aim of this study was to assess the long-term effects of smoking and to investigate the permanence of this damage to the oral microcirculation. MATERIAL AND METHODS We recruited 75 patients and divided them into 3 groups: group 1 was composed of 25 healthy non-smokers, group 2 was composed of 25 healthy current smokers, and group 3 was composed of 25 healthy ex-smokers. Video-capillaroscopic examination was performed on all patients. The video-capillaroscopic investigation was performed on patients in sitting position, always with the same light source, at the same room temperature (23°C), in the morning, with the same operator (GAS), and was repeated many times for every area under investigation. An enlargement of 200× allowed us to explore point-by-point all the morpho-structural characteristics of the capillaroscopic field. For non-parametric data, we evaluated the visibility of the loops and their position in relation to the surface of the mucosa. The evaluated parametric data were length of capillary loop, diameter of the loop, capillary tortuosity, and capillary density. RESULTS Our study clearly shows there was no remission of vascular damage, even 13 years after smoking cessation. CONCLUSIONS Our research shows that that the effects of smoking are still visible in ex-smokers, even at 13 years after cessation and also that ex-smokers are still subject to the risk of oral pathologies in the interval of time that we considered.

Intestinal dysbiosis and hormonal neuroendocrine secretion in the fibromyalgic patient: Relationship and correlations.

Fibromyalgia is a rheumatic syndrome and its pathogenesis is controversial. The recent literature has placed considerable attention on the link between alteration of the intestinal microbiota and fibromyalgia, emphasizing the close connection between the neuroenteric system and the CNS. This study aims to evaluate the probable relationship between intestinal dysbiosis and altered secretion of hormones and vitamins such as cortisol, serotonin, Vitamin D and thyroid hormones in a patient with fibromyalgia.

Colorectal Carcinogenesis: Role of Oxidative Stress and Antioxidants.

One of the contributory causes of colon cancer is the negative effect of reactive oxygen species on DNA repair mechanisms. Currently, there is a growing support for the concept that oxidative stress may be an important etiological factor for carcinogenesis. The purpose of this review is to elucidate the role of oxidative stress in promoting colorectal carcinogenesis and to highlight the potential protective role of antioxidants. Several studies have documented the importance of antioxidants in countering oxidative stress and preventing colorectal carcinogenesis. However, there are conflicting data in the literature concerning its proper use in humans, since these studies did not yield definitive results and were performed mostly in vitro on cell populations, or in vivo in experimental animal models.

Posture and posturology, anatomical and physiological profiles: overview and current state of art.

BACKGROUND AND AIM OF WORK: posture is the position of the body in the space, and is controlled by a set of anatomical structures. The maintenance and the control of posture are a set of interactions between muscle-skeletal, visual, vestibular, and skin system. Lately there are numerous studies that correlate the muscle-skeletal and the maintenance of posture. In particular, the correction of defects and obstruction of temporomandibular disorders, seem to have an impact on posture. The aim of this work is to collect information in literature on posture and the influence of the stomatognathic system on postural system. METHODS: Comparison of the literature on posture and posturology by consulting books and scientific sites. RESULTS: the results obtained from the comparison of the literature show a discrepancy between the thesis. Some studies support the correlation between stomatognathic system and posture, while others deny such a correlation. CONCLUSIONS: further studies are necessary to be able to confirm one or the other argument.

Doxorubicin anti-tumor mechanisms include Hsp60 post-translational modifications leading to the Hsp60/p53 complex dissociation and instauration of replicative senescence.

The chaperone Hsp60 is pro-carcinogenic in certain tumor types by interfering with apoptosis and with tumor cell death. In these tumors, it is not yet known whether doxorubicin anti-tumor effects include a blockage of the pro-carcinogenic action of Hsp60. We found a doxorubicin dose-dependent viability reduction in a human lung mucoepidermoid cell line that was paralleled by the appearance of cell senescence markers. Concomitantly, intracellular Hsp60 levels decreased while its acetylation levels increased. The data suggest that Hsp60 acetylation interferes with the formation of the Hsp60/p53 complex and/or promote its dissociation, both causing an increase in the levels of free p53, which can then activate the p53-dependent pathway toward cell senescence. On the other hand, acetylated Hsp60 is ubiquitinated and degraded and, thus, the anti-apoptotic effect of the chaperonin is abolished with subsequent tumor cell death. Our findings could help in the elucidation of the molecular mechanisms by which doxorubicin counteracts carcinogenesis and, consequently, it would open new roads for the development of cancer treatment protocols targeting Hsp60.

Nutrition, oxidative stress and intestinal dysbiosis: Influence of diet on gut microbiota in inflammatory bowel diseases.

BACKGROUND: Microbiota refers to the population of microorganisms (bacteria, viruses and fungi) that inhabit the entire gastrointestinal tract, more particularly the colon whose role is to maintain the integrity of the intestinal mucosa and control the proliferation of pathogenic bacteria. Alteration in the composition of the gut microbiota is called dysbiosis. Dysbiosis redisposes to inflammatory bowel diseases such as ulcerative colitis, Crohn disease and indeterminate colitis. METHODS: The purpose of this literature review is to elucidate the influence of diet on the composition of the gastrointestinal microbiota in the healthy gut and the role of diet in the development of dysbiosis. CONCLUSION: The "Western diet", in particular a low - fiber high fat/high carbohydrate diet is one factor that can lead to severe dysbiosis. In contrast, "mediterranean" and vegetarian diets that includes abundant fruits, vegetables, olive oil and oily fish are known for their anti-inflammatory effects and could prevent dysbiosis and subsequent inflammatory bowel disease.

The long-term effects of probiotics in the therapy of ulcerative colitis: A clinical study.

AIM: Intestinal dysbiosis seems to be the leading cause of inflammatory bowel diseases, and probiotics seems to represent the proper support against their occurrence. Actually, probiotic blends and anti-inflammatory drugs represent a weapon against inflammatory bowel diseases. The present study evaluates the long-term (2 years) effects of combination therapy (mesalazine plus a probiotic blend of Lactobacillus salivarius, Lactobacillus acidophilus and Bifidobacterium bifidus strain BGN4) on ulcerative colitis activity. METHOD: Sixty patients with moderate-to-severe ulcerative colitis were enrolled: 30 of them were treated with a single daily oral administration of mesalazine 1200 mg; 30 patients received a single daily oral administration of mesalazine 1200 mg and a double daily administration of a probiotic blend of Lactobacillus salivarius, Lactobacillus acidophilus and Bifidobacterium bifidus strain BGN4. The treatment was carried out for two years and the clinical response evaluated according to the Modified Mayo Disease Activity Index. RESULTS: All patients treated with combination therapy showed better improvement compared to the controls. In particular, the beneficial effects of probiotics were evident even after two years of treatment. CONCLUSIONS: A long-term treatment modality of anti-inflammatory drugs and probiotics is viable and could be an alternative to corticosteroids in mild-to moderate ulcerative colitis.

Quantitative patterns of Hsps in tubular adenoma compared with normal and tumor tissues reveal the value of Hsp10 and Hsp60 in early diagnosis of large bowel cancer.

Large bowel carcinogenesis involves accumulation of genetic alterations leading to transformation of normal mucosa into dysplasia and, lastly, adenocarcinoma. It is pertinent to elucidate the molecular changes occurring in the pre-neoplastic lesions to facilitate early diagnosis and treatment. Heat shock proteins (Hsps), many of which are molecular chaperones, are implicated in carcinogenesis, and their variations with tumor progression encourage their study as biomarkers. There are many reports on Hsps and cancer but none to our knowledge on their systematic quantification in pre-neoplastic lesions of the large bowel. We performed immunohistochemical determinations of Hsp10, Hsp60, Hsp70, and Hsp90 in biopsies of large bowel tubular adenomas with moderate grade of dysplasia and compared to normal mucosa and adenocarcinoma with a moderate grade of differentiation (G2). A significant elevation of Hsp10 and Hsp60 only, i.e., in the absence of elevation of Hsp70 or Hsp90, in both epithelium and lamina propria was found in tubular adenoma by comparison with normal mucosa. In contrast, adenocarcinoma was characterized by the highest levels of Hsp10 and Hsp60 in epithelium and lamina propria, accompanied by the highest levels of Hsp70 only in epithelium and of Hsp90 only in lamina propria, by comparison with normal and tubular adenoma counterparts. Hsp10 and Hsp60 are promising biomarkers for early diagnosis of tubular adenoma and for its differentiation from more advanced malignant lesions. Hsp10 and Hsp60 may be implicated in carcinogenesis from its very early steps and, thus, are potentially convenient targets for therapy.

Simple and fast orotracheal intubation procedure in rats.

INTRODUCTION: Endotracheal intubation in the rat is difficult because of the extremely small size of anatomical structures (oral cavity, epiglottis and vocal cords), small inlet for an endotracheal tube and the lack of proper technical instruments. MATERIAL AND METHODS: In this study we used seventy rats weighting 400-500 g. The equipment needed for the intubation was an operating table, a longish of cotton, a cotton tip, orotracheal tube, neonatal laryngoscope blades, KTR4 small animal ventilator and isoflurane for inhalation anaesthesia. Premedication was carried out by medetomidine hydrochloride 1 mg/mL; then, thanks to a closed glass chamber, a mixture of oxygen and isoflurane was administered. By means of a neonatal laryngoscope the orotracheal tube was advanced into the oral cavity until the wire guide was visualized trough the vocal cords; then it was passed through them. The tube was introduced directly into the larynx over the wire guide; successively, the guide was removed and the tube placed into the trachea. Breathing was confirmed using a glove, cut at the end of a finger, simulating a small balloon. RESULTS: We achieved a fast and simple orotracheal intubation in all animals employed. CONCLUSIONS: We believe that our procedure is easier and faster than those previously reported in scientific literature.

Comparative analysis of the structure of temporomandibular joint in human and rabbit.

In order to increase knowledge on the morphology and structure of the articular disc of the TMJ for a better understanding of the functional role of the same, it proceeded with an investigation on histological samples in the block of 'TMJ and periarticular tissues of adult rabbits and human fetuses at different stage of development.

Comparative analysis of Hsp10 and Hsp90 expression in healthy mucosa and adenocarcinoma of the large bowel.

BACKGROUND: Heat shock proteins (Hsps) assist other proteins in their folding and drive the degradation of defective proteins. During evolution, these proteins have also acquired other roles. Hsp10 is involved in immunomodulation and tumor progression. Hsp90 stabilizes a range of "client" proteins involved in cell signaling. The present study evaluated the expression levels of Hsp10 and Hsp90 in normal mucosa and adenocarcinoma samples of human large bowel. MATERIALS AND METHODS: Samples of normal mucosa and adenocarcinoma were collected and Reverse transcriptase-polymerase chain reaction RT-PCR, western blotting (WB) analyses, as well as immunohistochemistry were performed to evaluate the expression levels of Hsp10 and Hsp90. RESULTS: RT-PCR showed a higher gene expression of Hsp10 and Hsp90 in adenocarcinoma samples compared to healthy mucosa. WB results confirmed these findings. Immunohistochemistry revealed higher levels of Hsp10 in adenocarcinoma in both the epithelium and the lamina propria, while Hsp90 expression was higher in the adenocarcinoma samples only in the lamina propria. CONCLUSION: Hsp10 and Hsp90 may be involved in large bowel carcinogenesis.