Exploring the Link between Helicobacter pylori, Gastric Microbiota and Gastric Cancer.

Gastric cancer (GC) still represents one of the leading causes of cancer-related mortality and is a major public health issue worldwide. Understanding the etiopathogenetic mechanisms behind GC development holds immense potential to revolutionize patients' treatment and prognosis. Within the complex web of genetic predispositions and environmental factors, the connection between Helicobacter pylori (H. pylori) and gastric microbiota emerges as a focus of intense research investigation. According to the most recent hypotheses, H. pylori triggers inflammatory responses and molecular alterations in gastric mucosa, while non-Helicobacter microbiota modulates disease progression. In this review, we analyze the current state of the literature on the relationship between H. pylori and non-Helicobacter gastric microbiota in gastric carcinogenesis, highlighting the mechanisms by which microecological dysbiosis can contribute to the malignant transformation of the mucosa.

A holistic evaluation of patients with chronic Hepatitis D virus (HDV) infection enrolled in the Italian PITER-B and delta cohort.

BACKGROUND AND AIMS: We aimed to characterize the epidemiologic and comorbidities profiles of patients with chronic Hepatitis D (CHD) followed in clinical practice in Italy and explored their interferon (IFN) eligibility. METHODS: This was a cross-sectional study of the PITER cohort consisting of consecutive HBsAg-positive patients from 59 centers over the period 2019-2023. Multivariable analysis was performed by logistic regression model. RESULTS: Of 5492 HBsAg-positive enrolled patients, 4152 (75.6%) were screened for HDV, 422 (10.2%) were anti-HDV positive. Compared with HBsAg mono-infected, anti-HDV positive patients were more often younger, non-Italians, with a history of drug use, had elevated alanine transaminase (ALT), cirrhosis, or hepatocellular carcinoma (HCC). Compared with Italians, anti-HDV positive non-Italians were younger (42.2% age ≤ 40 years vs. 2.1%; P < 0.001), more often females (males 43.0% vs. 68.6%; P < 0.001) with less frequent cirrhosis and HCC. HDV-RNA was detected in 63.2% of anti-HDV-positive patients, who were more likely to have elevated ALT, cirrhosis, and HCC. Extrahepatic comorbidities were present in 47.4% of anti-HDV positive patients and could affect the eligibility of IFN-containing therapies in at least 53.0% of patients in care. CONCLUSIONS: CHD affects young, foreign-born patients and older Italians, of whom two-thirds had cirrhosis or HCC. Comorbidities were frequent in both Italians and non-Italians and impacted eligibility for IFN.

Bone Marrow of Contention: A Rare Case of Recurrent Acute Hepatitis.

Hepatitis-associated aplastic anemia is a well-recognized clinical syndrome in which marrow failure follows the development of hepatitis. Although aplastic anemia is intimately related to paroxysmal nocturnal hemoglobinuria, until now, no cases of PNH-associated hepatitis have been described. We report a case of recurrent acute hepatitis preceding the clinical onset of PNH. Treatment of PNH with the complement inhibitor eculizumab (Soliris®) prevented both recurrences of episodes of intravascular hemolysis and liver enzyme alteration. This is the first known published case of PNH-associated hepatitis.

Pharmacological treatment of gastrointestinal bleeding due to angiodysplasias: A position paper of the Italian Society of Gastroenterology (SIGE).

Angioectasias (AD) belong to benign vascular malformations of the gastrointestinal tract and are responsible for about 4-7% of upper non variceal bleeding, 30-40% of small bowel occult bleeding and 3-40% of colonic bleeding episodes. Gastrointestinal haemorrhage secondary to AD represents an important diagnostic and therapeutic problem that negatively impacts on the quality of life of patients and heath care costs. Endoscopic interventions are the mainstay in both diagnosis and treatment of vascular malformations. However, in a substantial percentage of the cases, age of the patients, comorbidities, clinical severity of anaemia and blood loss as well as size, site and number of lesions prevent this therapeutic approach. Hormonal therapy, thalidomide and somatostatin analogues have been investigated for their potential role as rescue therapies in controlling AD bleeding although, thus far, no recommendations have been provided on their use in this clinical setting. In order to implement appropriate prescription of pharmacological agents to manage gastrointestinal bleeding due to ADs, the Italian Society of Gastroenterology (SIGE) nominated a panel of experts who reviewed the available clinical literature and produced practical clinical recommendations.

The gut microbiota: A new potential driving force in liver cirrhosis and hepatocellular carcinoma.

The gut microbiota has recently been recognized as a major environmental factor in the pathophysiology of many human diseases. The anatomical and function connection existing between gut and liver provides the theoretical basis to assume the liver is a major target for gut microbes. In the last decades, numerous studies reported an altered composition of gut microbiota in patients with liver cirrhosis and a progressively marked dysbiosis with worsening of the liver disease. The risk of developing hepatocellular carcinoma, the deadliest complication of liver cirrhosis, is widely variable among cirrhotic patients, thus suggesting a complexity of genetic and environmental factors implicated in hepatocarcinogenesis. Gut microbiota is now emerging as a plausible candidate to explain this variability. In this manuscript we review the human and the experimental evidence supporting the potential implication of gut microbiota in the promotion, progression and complication of liver disease.

Lactobacillus casei DG and its postbiotic reduce the inflammatory mucosal response: an ex-vivo organ culture model of post-infectious irritable bowel syndrome.

BACKGROUND: The evidence on the role of gut microbiota in post-infectious irritable bowel syndrome (PI-IBS) is convincing. Lactobacillus spp. positively affect IBS symptoms, although the mechanisms through which probiotics exert their beneficial effects are largely unknown. The aim of the study is to evaluate the role of Lactobacillus casei DG (LC-DG) and its postbiotic (PB) in modulating the inflammatory/immune-response in PI-IBS in an ex-vivo organ culture model. METHODS: Ex vivo cultures of ileal and colonic mucosa from 10 PI-IBS, diarrhea predominant subtype (D) patients, and 10 healthy controls (HC) were treated with LPS, LC-DG and PB. Interleukin (IL)-1α, IL-6, IL-8 and IL-10 mRNA levels were assessed by real-time PCR and Toll like receptor 4 (TLR-4) protein expression by Western blotting. RESULTS: At baseline, IL-1α, IL-6 and IL-8 mRNA levels as well as TLR-4 protein expression were significantly higher while IL-10 mRNA levels were lower in PI-IBS D than in HC in both ileum and colon. LC-DG and PB significantly reduced the mRNA levels of pro-inflammatory cytokines and TLR-4 while increased that of IL-10 after LPS stimulation. The protective effect was more pronounced for PB than LC-DG treatment. CONCLUSION: LC-DG and its PB attenuate the inflammatory mucosal response in an ex-vivo organ culture model of PI-IBS D.

A microbiota-centric view of diseases of the upper gastrointestinal tract.

The distinctive anatomy and physiology of the upper gastrointestinal tract and the difficulty of obtaining samples led to the theory that it was bacteria free. However, multiomics studies are indicating otherwise. Although influenced by both oral and gastric bacteria, the resident microbial ecosystem in the oesophagus is dominated by Streptococcus. A shift from Gram-positive to Gram-negative bacteria occurs in oesophagitis and Barrett's oesophagus, and this shift might be involved in the pathogenesis of oesophageal adenocarcinoma. The gastric microenvironment is populated by microbial communities mainly of the Firmicutes, Actinobacteria, Bacteroidetes, and Proteobacteria phyla and species of the Lactobacillus, Streptococcus, and Propionibacterium genera. The composition of gastric microbiota is highly dynamic, and is influenced by acid suppression, gastric inflammation, and Helicobacter pylori. Duodenal microbes are also implicated in the onset and outcome of coeliac disease. Bacteria of the genera Bacteroides, Clostridium, and Staphylococcus dominate the duodenal flora in active coeliac disease whereas lactobacilli and bifidobacteria decrease. Although knowledge of the composition of the microbiota of the upper gastrointestinal tract has advanced substantially, this information is far from being translated to the clinical setting. In this Review, we assess the data related to the potential contribution of microbes to the susceptibility for and pathogenesis of upper gastrointestinal diseases.

Screening for and surveillance of gastric cancer.

Although the prevalence of gastric cancer (GC) progressively decreased during the last decades, due to improved dietary habit, introduction of food refrigeration and recovered socio-economic level, it still accounts for 10% of the total cancer-related deaths. The best strategy to reduce the mortality for GC is to schedule appropriate screening and surveillance programs, that rises many relevant concerns taking into account its worldwide variability, natural history, diagnostic tools, therapeutic strategies, and cost-effectiveness. Intestinal-type, the most frequent GC histotype, develops through a multistep process triggered by Helicobacter pylori (H. pylori) and progressing from gastritis to atrophy, intestinal metaplasia (IM), and dysplasia. However, the majority of patients infected with H. pylori and carrying premalignant lesions do not develop GC. Therefore, it remains unclear who should be screened, when the screening should be started and how the screening should be performed. It seems reasonable that screening programs should target the general population in eastern countries, at high prevalence of GC and the high-risk subjects in western countries, at low prevalence of GC. As far as concern surveillance, currently, we are lacking of standardized international recommendations and many features have to be defined regarding the optimal diagnostic approach, the patients at higher risk, the best timing and the cost-effectiveness. Anyway, patients with corpus atrophic gastritis, extensive incomplete IM and dysplasia should enter a surveillance program. At present, screening and surveillance programs need further studies to draw worldwide reliable recommendations and evaluate the impact on mortality for GC.

Overexpression of chromatin assembly factor-1 p60, poly(ADP-ribose) polymerase 1 and nestin predicts metastasizing behaviour of oral cancer.

AIMS: The natural history of oral squamous cell carcinomas (OSCCs) is variable and difficult to predict. This study aimed to assess the value of the expression of poly(ADP-ribose) polymerase 1 (PARP-1), chromatin assembly factor-1 (CAF-1)/p60 and the stem cell markers CD133, CD166, CD44, CD44v6 and nestin as markers of outcome and progression-free survival in OSCC patients. METHODS: Clinical data were collected from 66 patients (41 male and 25 female, aged 29-92 years) who underwent surgery for OSCC of the tongue, floor, lips, and palate. During follow-up (range: 12-131 months), 14 patients experienced relapse/metastasis and/or death. The study was performed by immunohistochemistry on paraffin-embedded tumour tissues, western blot analysis of tumour protein lysates and human cell lines, and RNA silencing assays. In addition, the human papillomavirus (HPV) status of primary tumours was evaluated by immunohistochemistry and viral subtyping. Univariate and multivariate analyses were performed to determine the correlation between these parameters and the clinical and pathological variables of the study population. RESULTS AND CONCLUSIONS: We found that a PARP-1(high) /CAF-1 p60(high) /nestin(high) phenotype characterized the OSCCs with the worst prognosis (all HPV-negative). This may be of benefit in clinical management, since radio-enhancing anti-PARP-1 and/or anti-CAF-1/p60 agents may allow radioresistance to be bypassed in the nestin-overexpressing, metastasizing OSCC cells.

MDR1-P-glycoprotein behaves as an oncofetal protein that promotes cell survival in gastric cancer cells.

P-glycoprotein (P-gp), traditionally linked to cancer poor prognosis and multidrug resistance, is undetectable in normal gastric mucosa and overexpressed in gastric cancer (GC). We propose that P-gp may be involved in Helicobacter pylori (Hp)-related gastric carcinogenesis by inhibiting apoptosis. Aim of the study was to evaluate the expression of P-gp in fetal stomach and in Hp-related gastric carcinogenesis, the epigenetic control of the multi-drug resistance-1 (MDR1) gene, the localization and interaction between P-gp and Bcl-x(L) and the effect of the selective silencing of P-gp on cell survival. P-gp and Bcl-xl expression was evaluated by immunohistochemistry on 28 spontaneously abortive human fetuses, 66 Hp-negative subjects, 138 Hp-positive chronic gastritis (CG) of whom 28 with intestinal metaplasia (IM) and 45 intestinal type GCs. P-gp/Bcl-x(L) colocalization was investigated by confocal immunofluorescence microscopy and protein-protein interaction by co-immunoprecipitation, in basal conditions and after stress-induced apoptosis, in GC cell lines AGS and MKN-28 and hepatocellular carcinoma cell line Hep-G2. The role of P-gp in controlling apoptosis was evaluated by knocking down its expression with a specific small interfering RNAs in stressed AGS and MKN-28 cell lines. P-gp is expressed in the gastric mucosa of all human fetuses while, it is undetectable in adult normal mucosa and re-expressed in 30/110 Hp-positive non-IM-CG, 28/28 IM-CG and 40/45 GCs. P-gp expression directly correlates with that of Bcl-x(L) and with the promoter hypomethylation of the MDR1 gene. In GC cell lines, P-gp is localized on the plasma membrane and mitochondria where it colocalizes with Bcl-x(L). Co-immunoprecipitation confirms the physical interaction between P-gp and Bcl-x(L) in AGS, MKN-28 and Hep-G2, at both basal level and after stress-induced apoptosis. The selective silencing of P-gp sensitizes GC cells to stress-induced apoptosis. P-gp behaves as an oncofetal protein that, by cross-talking with Bcl-x(L), acts as an anti-apoptotic agent in Hp-related gastric carcinogenesis.

Cancer stem cell hypothesis and gastric carcinogenesis: Experimental evidence and unsolved questions.

Traditionally, the clonal evolution model has been used to explain gastric cancer (GC) growth dynamics. According to this model, GC cells result from multiple mutations over time resulting in a population of continually diversifying cells. This heterogeneity enables the survival of different clones under particular conditions allowing growth at metastatic locations or resistance to chemotherapeutics. Cancer stem cell (CSC) theory completely overturns this traditional understanding of cancer suggesting that only CSCs can self-renew and promote tumor growth. CSCs are relatively refractory to conventional therapies, thus explaining why anti-cancer therapies are far from curative and why relapses of cancer are frequent. The identification of the CSC component of a tumor might, thus, open new therapeutic perspective based on the selective targeting of this small population of cells. In this review we examine the current scientific evidence supporting the existence of CSC in gastric tumors and analyze the main unsolved questions of this difficult field of cancer research.

CD133 and CD44 cell surface markers do not identify cancer stem cells in primary human gastric tumors.

Emerging evidence suggests that tumors contain and are driven by a cellular component that displays stem cell properties, the so-called cancer stem cells (CSCs). CSCs have been identified in several solid human cancers; however, there are no data about CSCs in primary human gastric cancer (GC). By using CD133 and CD44 cell surface markers we investigated whether primary human GCs contain a cell subset expressing stem-like properties and whether this subpopulation has tumor-initiating properties in xenograft transplantation experiments. We examined tissues from 44 patients who underwent gastrectomy for primary GC. The tumorigenicity of the cells separated by flow cytometry using CD133 and CD44 surface markers was tested by subcutaneous or intraperitoneum injection in NOD/SCID and nude mice. GCs included in the study were intestinal in 34 cases and diffuse in 10 cases. All samples contained surface marker-positive cells: CD133(+) mean percentage 10.6% and CD133(+)/CD44(+) mean percentage 27.7%, irrespective of cancer phenotype or grade of differentiation. Purified CD133(+) and CD133(+)/CD44(+) cells, obtained in sufficient number only in 12 intestinal type GC cases, failed to reproduce cancer in two mice models. However, the unseparated cells produced glandular-like structures in 70% of the mice inoculated. In conclusion, although CD133(+) and CD133(+)/CD44(+) were detectable in human primary GCs, they neither expressed stem-like properties nor exhibited tumor-initiating properties in xenograft transplantation experiments.

13C-aminopyrine breath test accurately predicts long-term outcome of chronic hepatitis C.

BACKGROUND & AIMS: Although numerous non-invasive tests are currently available to explore liver function and disease activity in patients with HCV-related chronic diseases, none of these indicate the likelihood of disease progression in the individual patient. We aimed at assessing the prognostic ability of (13)C(2)-aminopyrine breath test ((13)C-ABT) in the prediction of liver fibrosis progression in patients with HCV chronic hepatitis who prospectively entered a long-term follow-up. METHODS: Fifty patients with HCV-related chronic disease who underwent paired liver biopsy (at baseline and after a mean period of 86 months) were included in the study. (13)C-ABT was carried out at baseline and every 3 years. Histological progression was defined as increase of at least 2 fibrosis units according to Ishak score. RESULTS: Fourteen patients progressed of at least 2 fibrosis units during the follow-up. These patients were more frequently infected with a HCV-1b genotype and had, at baseline, a significantly older age, higher BMI, AST levels, and AST to platelet ratio index (APRI). (13)C-ABT was altered in 57% of cases at baseline and in 100% of the cases at 3-year follow-up. In the univariate analysis, age (p=0.005), BMI (p=0.006), platelet count (p=0.03), AST (p=0.012) and ALT (p=0.04) levels, APRI (p=0.03), and baseline (13)C-ABT results (p<0.0001) were all independently associated with progression of liver fibrosis. By Cox's multiple regression analysis, the (13)C-ABT was the only covariate that significantly predicted liver fibrosis progression (HR 6.7; 95% CI 2.3-20.1; p<0.001). CONCLUSIONS: (13)C-ABT accurately predicts the risk of disease progression in patients with HCV-related chronic hepatitis.

Pseudopneumoperitoneum in chronic intestinal pseudo-obstruction: a case report.

Chronic intestinal pseudo-obstruction (CIPO) is a rare disease due to a severe gastrointestinal motility disorder which may mimic, on both clinical and radiological grounds, mechanical obstruction. We report a case of a 26-year-old woman who presented to our institution for plain abdominal radiography for referred long-lasting constipation with recurrent episodes of abdominal pain and distension. At X-ray, performed both in the upright and supine position, an isolated air-fluid level was depicted in the left flank, together with a number of radiological signs suggestive of pneumoperitoneum. First, subphrenic radiolucency could be observed in the upright film. Second, the intestinal wall of some jejunal loops appeared to be outlined in the right flank. Third, the inferior cardiac border was clearly depicted in the upright film. The patient however had no evidence of peritoneal signs but only hypoactive bowel movements. Unenhanced multi-detector computed tomography (MDCT) of the abdomen and pelvis was therefore performed. MDCT revealed abnormal air-driven distension of the small and large bowel, without evidence of extra-luminal air. All radiological signs of pneumoperitoneum turned out to be false-positive results. The patient was submitted to pan-colonoscopy and to anorectal manometry to rule out Hirshprung's disease, and was finally discharged with a diagnosis of CIPO.

Global DNA hypomethylation is an early event in Helicobacter pylori-related gastric carcinogenesis.

AIM: Cancer, particularly gastric cancer (GC), is prevalently an epigenetic phenomenon that is dependent on an altered DNA methylation pattern. In gastric carcinogenesis, many genes show aberrant methylation; however, none of them may be used as a biomarker of cancer risk and progression. The authors aimed to evaluate the global DNA methylation of gastric mucosa in Helicobacter pylori (Hp)-related chronic gastritis, in GC and in 10 patients with preneoplastic lesions (ie, atrophy and intestinal metaplasia) followed up for 10 years. METHODS: The authors analysed 93 dyspeptic patients who underwent upper endoscopy, 41 surgical GC samples and 10 patients with preneoplastic gastric lesions followed up for 10 years after successful Hp eradication therapy. Global DNA methylation status and surrogate markers of cell proliferation and apoptosis were evaluated by immunohistochemistry using the anti-5-methylcytosine (5-MC), anti-Ki-67 and anti-p53 (anti-apoptotic marker)-specific antibodies, respectively. RESULTS: Global DNA methylation of gastric mucosa gradually decreased from normal mucosa to Hp-positive gastritis, Hp-positive chronic atrophic gastritis, independent of Cag-A status and GC; however, the variation was significant (p<0.05) only between Hp-negative subjects and Hp-positive chronic gastritis. Interestingly, the 5-MC immunostaining was absent in areas of intestinal metaplasia. In the 10 patients with preneoplastic lesions, global DNA methylation decreased over time despite the eradication of Hp infection, but reached significance only at 10 years versus baseline. The 5-MC immunostaining negatively correlated with Ki-67 and p53 expression in all groups. CONCLUSION: Global DNA hypomethylation is an early molecular event in Hp-related gastric carcinogenesis. Further studies with more cases and a longer follow-up are needed to establish the potential GC predictive role of DNA hypomethylation.

Clinicopathologic implications of the epidermal growth factor receptor, cyclooxygenase 2 expression, and human papillomavirus status in squamous cell carcinoma of the uterine cervix in the elderly.

OBJECTIVES: To find information on invasive squamous cervical carcinoma in the elderly, 110 invasive squamous cervical carcinomas obtained from 2 groups of patients (aged <60 and >60 years) were analyzed for human papillomavirus (HPV) status by polymerase chain reaction study, for immunohistochemical epidermal growth factor receptor (EGFR), cyclooxygenase 2 (Cox-2) expression, and clinicopathologic features. METHODS: The HPV status and the expression of Cox-2 and EGFR in the younger and older women were compared and correlated with the grading, staging neoplasm, and lymph nodal status, using Fisher test and Spearman nonparametric correlation test. Overall survival curves were drawn using Kaplan-Meier estimates and were compared using log-rank tests in the whole series of 110 patients. Multinomial logistic regression was also used. RESULTS AND CONCLUSIONS: The number of neoplasms with higher staging was significantly greater than those in the younger women (P = 0.04). The mortality was higher in the older group than in the younger patients (P = 0.006).In the elderly, the presence of HPV DNA in 65% of cases, and in the absence of sexual activity, could be due to reactivation of latent HPV infection, which might be due to an impairment of host immunologic response.The overexpression of Cox-2 in a number of cases was significantly higher in the older group than in the younger group (P = 0.032, Fisher exact test), but this immunoreactivity is not related to the staging, grading, EGFR expression, or to the presence of HPV.The simultaneous expression of Cox-2 and EGFR had a poor prognostic significance, showing lower survival rates than cases without this immunoreactivity (P = 0.002), on univariate analysis.On multivariate analysis, Cox-2 and EGFR immunopositivity did not reveal any correlation between these markers and prognosis probably because the number of cases considered was not particularly high.

The proliferation marker Chromatin Assembly Factor-1 is of clinical value in predicting the biological behaviour of salivary gland tumours.

Salivary gland tumours (SGT) constitute a diagnostically challenging group of neoplasms with frequently unpredictable clinical outcome. The proliferation rate facilitates the identification of aggressive SGT. The Chromatin Assembly Factor-1 (CAF-1) is a major epigenetic regulator of nuclear chromatin organization during DNA replication. It plays a critical function in human tumourigenesis and has been proposed as a new proliferation and prognostic marker for some malignancies. This study focused on the role of CAF-1/p60 protein as a marker of clinical value for SGT. The expression of CAF-1/p60 was evaluated by immunohistochemistry on a retrospective series of 362 surgically excised benign and malignant SGT with different histogenesis and, when available, on fine-needle pre-surgical cytological biopsies. The resulting data were compared with traditional prognostic parameters, including the expression of the routine proliferation marker ki67/MIB1. CAF-1/p60 was detectable in all SGT, with highest degree of expression in metastasizing malignant tumours. Moreover, the cases of benign tumours which progressed to carcinoma during the follow-up, showed significantly higher CAF-1/p60 expression than non-progressing benign SGT, both on histological sections and cytological smears of the primary tumour. Cox's multiple regression analysis selected CAF-1/p60 expression as the best independent predictor of cancer development for benign SGT (p<0.0001), and the best independent predictor of metastasis onset for malignant tumours (p<0.0004). Overexpression of CAF-1/p60, on histological and/or cytological samples, characterizes malignant SGT with aggressive behaviour, irrespective of their specific histotype, and allows the early diagnosis of progression toward malignancy of morphologically benign tumours.

Protective effects of Lactobacillus paracasei F19 in a rat model of oxidative and metabolic hepatic injury.

The liver is susceptible to such oxidative and metabolic stresses as ischemia-reperfusion (I/R) and fatty acid accumulation. Probiotics are viable microorganisms that restore the gut microbiota and exert a beneficial effect on the liver by inhibiting bacterial enzymes, stimulating immunity, and protecting intestinal permeability. We evaluated Lactobacillus paracasei F19 (LP-F19), for its potential protective effect, in an experimental model of I/R (30 min ischemia and 60 min reperfusion) in rats fed a standard diet or a steatogen [methionine/choline-deficient (MCD)] diet. Both groups consisted of 7 sham-operated rats, 10 rats that underwent I/R, and 10 that underwent I/R plus 8 wk of probiotic dietary supplementation. In rats fed a standard diet, I/R induced a decrease in sinusoid perfusion (P < 0.001), severe liver inflammation, and necrosis besides an increase of tissue levels of malondialdehyde (P < 0.001), tumor necrosis factor-alpha (P < 0.001), interleukin (IL)-1beta (P < 0.001), and IL-6 (P < 0.001) and of serum levels of transaminase (P < 0.001) and lipopolysaccharides (P < 0.001) vs. sham-operated rats. I/R also induced a decrease in Bacterioides, Bifidobacterium, and Lactobacillus spps (P < 0.01, P < 0.001, and P < 0.001, respectively) and an increase in Enterococcus and Enterobacteriaceae (P < 0.01 and P < 0.001, respectively) on intestinal mucosa. The severity of liver and gut microbiota alterations induced by I/R was even greater in rats with liver inflammation and steatosis, i.e., MCD-fed animals. LP-F19 supplementation significantly reduced the harmful effects of I/R on the liver and on gut microbiota in both groups of rats, although the effect was slightly less in MCD-fed animals. In conclusion, LP-F19 supplementation, by restoring gut microbiota, attenuated I/R-related liver injury, particularly in the absence of steatosis.

BAG3 protein delocalisation in prostate carcinoma.

Despite the progressive increase of early diagnosis, a subset of prostate cancers show a metastasizing and lethal course, not always predictable upon the traditional prognostic parameters. The object of this study was to investigate the role of the survival co-chaperone protein BAG3 as a new prognostic marker for prostate cancer. BAG3 was detected by immunohistochemistry in 55 specimens of surgically removed prostate carcinomas and in 15 surgical specimens of non-neoplastic prostate tissues. Results were compared with clinic-pathological data and outcome of patients and statistically evaluated. BAG3 resulted expressed in all the cases: Non-neoplastic prostate tissue showed a cytoplasmatic staining with apical reinforcement, a finding which appears consistent with the reported connection of the protein with the membrane focal cell-adhesion complexes. In prostate carcinomas, BAG3 showed a progressive decrease of the expression level from well- to low-differentiated carcinoma, coupled with the loss of polarisation of the signal in metastasizing cases. These results indicate that BAG3 intra-cytoplasmic delocalisation is a specific feature of cancer versus non-neoplastic prostate and a candidate new marker for prediction of prostate cancer invasiveness and behaviour.

Molecular expression of Gastrokine 1 in normal mucosa and in Helicobacter pylori-related preneoplastic and neoplastic gastric lesions.

We have analyzed the expression of Gastrokine 1 (GKN1), one of the most abundant protein of gastric mucosa, in Helicobacter pylori-related preneoplastic and neoplastic gastric lesions. The GKN1 expression was downregulated in 36 H. pylori-positive patients with respect to 29 H. pylori-negative subjects as evaluated by Western blot, reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry, showing a progressive decrease from chronic gastritis to atrophy and intestinal metaplasia. Interestingly, in gastric cancer (GC) patients, GKN1 was undetectable in tissue tumoral areas but was instead expressed in the corresponding tissue non-tumoral areas. In conclusion our data suggests that GKN1 expression is related to the inflammatory damage of gastric mucosa and could be the related to the gastric cellular phenotype.