The role of multipotent cancer associated fibroblasts in hepatocarcinogenesis

The presence of tumor supporting cells in various cancer, including in hepatocellular carcinoma (HCC), has become an important target in the study of carcinogenesis. The cancer-associated fibroblast (CAF), one of the most important cellular components in the cancer stroma, might contribute to the progression of the disease due to its plasticity, a behavior of the stem cells. In this study, we investigate the significance of the CAF and its role in the HCC progression and metastasis. Methods: Primary CAF and non-tumoral fibroblast (NTF) from nine paired HCC and distant non-tumoral liver tissues were isolated and cultured. The cells were characterized by flow cytometry, RT-PCR, anchorage-independent assay and in vitro cells directed trans-differentiation. Co-culture study was performed in Transwell system and xenograft assay was performed in immunodeficient mice. Results: CAF and NTF were positive for CD90, CD44, \u3b1SMA, and vimentin and negative for CD34, CD45, CD117, and CD133. When stimulated, they showed the potential to differentiate into adipocytes, osteoblasts, and pancreatic cells. When co-cultured with human HCC cell lines, CAF up-regulated gene expressions of TGFB1 and FAP of HuH-7 and JHH-6 while NTF did not induced either of the genes. Xenograft assay showed that the CAF had the capacity to enter into circulation as confirmed by RT-PCR and DNA sequencing. Conclusion: Our data provides evidence of the plasticity of the CAF and the NTF as stem cells in the process of hepatocarcinogenesis and metastasis. These cells mutually interacts with HCC cells. Their trans-differentiation flexibility may induce a switch from normal to cancerous microenvironment

A story of liver and gut microbes: How does the intestinal flora affect liver disease? A review of the literature

Each individual is endowed with a unique gut microbiota (GM) footprint that mediates numerous host-related physiological functions, such as nutrient metabolism, maintenance of the structural integrity of the gut mucosal barrier, immunomodulation, and protection against microbial pathogens. Because of increased scientific interest in the GM, its central role in the pathophysiology of many intestinal and extraintestinal conditions has been recognized. Given the close relationship between the gastrointestinal tract and the liver, many pathological processes have been investigated in the light of a microbial-centered hypothesis of hepatic damage. In this review we introduce to neophytes the vast world of gut microbes, including prevalent bacterial distribution in healthy individuals, how the microbiota is commonly analyzed, and the current knowledge of the role of GM in liver disease pathophysiology. Also, we highlight the potentials and downsides of GM-based therapy

Pylephlebitis: A Systematic Review on Etiology, Diagnosis, and Treatment of Infective Portal Vein Thrombosis

Pylephlebitis, defined as infective thrombophlebitis of the portal vein, is a rare condition with an incidence of 0.37–2.7 cases per 100,000 person-years, which can virtually complicate any intra-abdominal or pelvic infections that develop within areas drained by the portal venous circulation. The current systematic review aimed to investigate the etiology behind pylephlebitis in terms of pathogens involved and causative infective processes, and to report the most common symptoms at clinical presentation. We included 220 individuals derived from published cases between 1971 and 2022. Of these, 155 (70.5%) were male with a median age of 50 years. There were 27 (12.3%) patients under 18 years of age, 6 (2.7%) individuals younger than one year, and the youngest reported case was only 20 days old. The most frequently reported symptoms on admission were fever (75.5%) and abdominal pain (66.4%), with diverticulitis (26.5%) and acute appendicitis (22%) being the two most common causes. Pylephlebitis was caused by a single pathogen in 94 (42.8%) cases and polymicrobial in 60 (27.2%) cases. However, the responsible pathogen was not identified or not reported in 30% of the included patients. The most frequently isolated bacteria were Escherichia coli (25%), Bacteroides spp. (17%), and Streptococcus spp. (15%). The treatment of pylephlebitis consists initially of broad-spectrum antibiotics that should be tailored upon bacterial identification and continued for at least four to six weeks after symptom presentation. There is no recommendation for prescribing anticoagulants to all patients with pylephlebitis. However, they should be administered in patients with thrombosis progression on repeat imaging or persistent fever despite proper antibiotic therapy to increase the rates of thrombus resolution or decrease the overall mortality, which is approximately 14%

Diverticular Disease and Rifaximin: An Evidence-Based Review

There have been considerable advances in the treatment of diverticular disease in recent years. Antibiotics are frequently used to treat symptoms and prevent complications. Rifaximin, a non-absorbable antibiotic, is a common therapeutic choice for symptomatic diverticular disease in various countries, including Italy. Because of its low systemic absorption and high concentration in stools, it is an excellent medicine for targeting the gastrointestinal tract, where it has a beneficial effect in addition to its antibacterial properties. Current evidence shows that cyclical rifaximin usage in conjunction with a high-fiber diet is safe and effective for treating symptomatic uncomplicated diverticular disease, while the cost-effectiveness of long-term treatment is unknown. The use of rifaximin to prevent recurrent diverticulitis is promising, but further studies are needed to confirm its therapeutic benefit. Unfortunately, there is no available evidence on the efficacy of rifaximin treatment for acute uncomplicated diverticulitis

MBL2 Genetic Variants in HCV Infection Susceptibility, Spontaneous Viral Clearance and Pegylated Interferon Plus Ribavirin Treatment Response

Hepatitis C is disease that damages the liver, and it is caused by the hepatitis C virus (HCV). The pathology became chronic in about 80% of the cases due to virus persistence in the host organism. The standard of care consists of pegylated interferon plus ribavirin; however, the treatment response is very variable and different host/viral factors may concur in the disease outcome. The mannosebinding protein C (MBL) is a component of the innate immune system, able to recognize HCV and consecutively activating the immune response. MBL is encoded by MBL2 gene, and polymorphisms, two in the promoter region (H/L and X/Y) and three in exon 1 (at codon 52, 54 and 57), have been described as functionally influencing protein expression. In this work, 203 Italian HCV patients and 61 healthy controls were enrolled and genotyped for the five MBL2 polymorphisms mentioned above to investigate their role in HCV infection susceptibility, spontaneous viral clearance and treatment response. MBL2 polymorphisms were not associated with HCV infection susceptibility and with spontaneous viral clearance, while MBL2 O allele, O/O genotype, HYO haplotype and DP combined genotype (all correlated with low or deficient MBL expression) were associated with sustained virological response. Moreover, a meta-analysis to assess the role of MBL2 polymorphisms in HCV infection susceptibility was also performed: YA haplotype could be associated with protection towards HCV infection

MiR-3201 as a Prognostic Blood Biomarker for Curative Treatments in Hepatocellular Carcinoma

Background: Hepatic resection, radiofrequency ablation (RF), and liver transplantation (LT) represent the only available curative treatments for early stage hepatocellular carcinoma (HCC). Various studies showed that the 5-year overall survival (OS) rate reaches ∼70% after resection and ∼60% after RF. Objective: To improve the success rate of curative therapies and consequently the OS, an improvement in patients' selection and management should be pursued. In this regard, microRNAs (miRNAs) can be helpful prognostic biomarkers. Materials and Methods: In this retrospective study, a miRNA array profiling was performed on 34 HCC blood samples which is collected before therapy (T0), 1 month (T1), and 6 months (T2) after curative treatments (resection and RF) to identify noninvasive biomarker candidates for therapy response and OS. MiRNAs were validated in 80 blood HCC samples using quantitative real-time PCR (qRT-PCR). Patients were divided into complete responder (CR) and partial responder and progressive disease (PRPD). Results: Among the selected miRNAs, miR-3201 is significantly associated with treatment response in the validation phase, showing a 23% reduction (P = .026) in CR compared to PRPD. MiR-3201 was able to distinguish CR from PRPD (area under the curve [AUC] = 0.69, 71% sensitivity, 70% specificity, P = .0036). Furthermore, lower levels of miR-3201 were associated with longer OS (hazard ratio [HR] = 2.61, P = .0006). Conclusions: Blood miR-3201 could be used as a prognostic biomarker for curative therapy response and OS in HCC

MicroRNAs as Regulators of Neo-Angiogenesis in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is a highly vascularized neoplasm. In the tumor niche, abundant angiogenesis is fundamental in providing nutrients for tumor growth and represents the first escape route for metastatic cells. Active angiogenesis, together with metastasis, are responsible for the reduction of recurrence-free survival of HCC. MicroRNAs (miRNAs) are small non-coding RNAs that have recently drawn attention in molecular targeted therapy or as diagnostic and prognostic biomarkers. MiRNA expression in HCC has been widely studied in the last decade. Some miRNAs have been found to be up- or down-regulated, besides association with apoptosis, metastasis progression and drug resistance have been found. This review article aims to summarize the angiogenetic process in tumor diseases and to update on what has been found in the vast world of HCC-related-miRNAs and, eventually, to report the latest finding on several miRNAs involved in HCC angiogenesis. We searched the state of the arts for the 12 miRNAs found to be involved with angiogenesis in HCC (miR-29b, miR-126-3p, miR-144-3p, miR-146a, miR-195, miR-199a-3p, miR-210-3p, miR-338- 3p, mir-491, mir-497, mir-638, mir-1301) and reported their main molecular targets and their overall effect in the sprouting of new vessels

The Matter of Future Heritage

In 2018, for the first time, the University of Bologna’s Board of PhD in Architecture and Design Culture assigned second-year PhD students the task of developing and managing an international conference and publishing its works. The organisers of the first edition of this initiative – Giacomo Corda, Pamela Lama, Viviana Lorenzo, Sara Maldina, Lia Marchi, Martina Massari and Giulia Custodi – have chosen to leverage the solid relationship between the Department of Architecture and the Municipality of Bologna to publish a call having to do with the European Year of Cultural Heritage 2018, in which the Municipality was involved. The theme chosen for the call, The Matter of Future Heritage, set itself the ambitious goal of questioning the future of a field of research – Cultural Heritage (CH) – that is constantly being  redefined. A work that was made particularly complex in Europe by the development of the H2020 programme, where the topic entered, surprisingly, not as a protagonist but rather as an articulation of other subjects that in the vision of the programme seemed evidently more urgent and, one might say, dominant. The resulting tensions have been considerable and with both negative and positive implications, all the more evident if we refer to the issues that are closest to us namely the city and the landscape

Epidemiology of hepatitis C virus infection

Although a lot of novel information and data on the epidemiology of hepatitis C virus (HCV) infection are available worldwide, the majority of these information are often fragmentary and sometimes contradictory. This review tries to highlight all the data available on the prevalence (i.e. the number of cases present in a known population), the risk factors, the natural history and the incidence (i.e. the number of new cases that occur every year) of HCV infection in the world, and particularly in Italy