Gastroenterology Insights

18 pages, 6739 KiB

Open AccessArticle

Differential Effects of Somatostatin on TNF Receptors and Apoptosis in Hepatocellular Carcinoma Cell Lines

by Maria Georgiadou, George Notas, Ioannis Tsomidis, Argyro Voumbouraki, Ioannis Drygiannakis, George Emmanouil and Elias Kouroumalis

Gastroenterol. Insights 2024, 15(3), 614-631; https://doi.org/10.3390/gastroent15030045 - 4 Jul 2024

Viewed by 599

Abstract

The anti-tumoral activity of somatostatin has been demonstrated in both animal experiments and human tumors. Clinical trials have reported conflicting results. We therefore hypothesized that somatostatin might have different effects in various hepatocellular carcinoma cells. Their clarification would possibly allow for the better [...] Read more.

The anti-tumoral activity of somatostatin has been demonstrated in both animal experiments and human tumors. Clinical trials have reported conflicting results. We therefore hypothesized that somatostatin might have different effects in various hepatocellular carcinoma cells. Their clarification would possibly allow for the better selection of patients suitable for the optimal treatment results. We studied the mRNA and protein expression of TNF receptors and the TNFa-induced apoptosis using the HepG2 and the Hep3B human hepatocellular carcinoma cells after incubation with the somatostatin analog octreotide. RT-PCR, Western blot, and parameters associated with apoptosis (NF-kB nuclear translocation, P65 Ser536 and P65 Ser468 phosphorylation, DNA fragmentation) were assessed. Only TNFR1 was constitutively present in the two cell lines. Octreotide incubation led to an earlier reduction in TNFR1 mRNA and protein in HepG2 compared to Hep3B cells (1 h and 6–12 h, respectively). NF-kB translocation to the nucleus was induced by TNFa and was more prominent in Hep3B. Translocation was unaffected by octreotide. Serine phosphorylation was significantly induced by TNFa and was more evident in the Hep3B cells. TNFa-induced Ser536 phosphorylation was inhibited by octreotide only in the HepG2 cells. DNA fragmentation was not influenced by either octreotide or TNFa in the HepG2 cells, but TNFa induced fragmentation in the Hep3B cells (1.8-fold increase) verified by the TUNEL index (43 compared to 19 for the HepG2 cells). Octreotide and TNFa co-incubation induced apoptosis in the HepG2 cells (1.7-fold increase compared to controls) but inhibited apoptosis in the Hep3B cells. We conclude that: (1) octreotide reduced TNFR1 receptor expression in both cell lines, (2) parameters of apoptosis were differentially affected by octreotide in the two cell lines, and (3) this might be a partial explanation for the conflicting results of somatostatin analog treatment in human hepatocellular carcinoma trials. Full article

(This article belongs to the Section Liver)

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15 pages, 703 KiB

Open AccessReview

Anabolic Androgenic Steroids and Hepatocellular Adenoma and Carcinoma: Molecular Mechanisms and Clinical Implications

by Luca Ielasi, Enrico Fulco, Nicola Reggidori, Marco Domenicali and Francesco Giuseppe Foschi

Gastroenterol. Insights 2024, 15(3), 599-613; https://doi.org/10.3390/gastroent15030044 - 4 Jul 2024

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Abstract

Anabolic androgenic steroids (AAS) are a class of hormones that are used for hormonal replacement therapy in cases of male hypogonadism and for a few other medical conditions, mainly anemias, as well as for the female-to-male transition process. At the same time, AAS [...] Read more.

Anabolic androgenic steroids (AAS) are a class of hormones that are used for hormonal replacement therapy in cases of male hypogonadism and for a few other medical conditions, mainly anemias, as well as for the female-to-male transition process. At the same time, AAS are widely abused for their muscle-building and strength-increasing properties. Among their side effects, androgens can exert a toxic effect on the liver, causing hepatotoxicity, but they can also induce hepatocyte proliferation and malignant transformation. Hepatocellular adenoma (HCA) and hepatocellular carcinoma (HCC) are two primary liver lesions that have been described as potentially related to AAS. This review provides an up-to-date analysis of how androgens can induce liver carcinogenesis and a comprehensive overview on the available data in the literature about AAS and primary liver tumors. Full article

(This article belongs to the Special Issue Feature Papers in Liver Research)

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11 pages, 2857 KiB

Open AccessArticle

Grading of Fatty Liver Based on Computed Tomography Hounsfield Unit Values versus Ultrasonography Grading

by Sultan Abdulwadoud Alshoabi, Reyan Mohammed Alharbi, Rufaydah Bader Algohani, Shahad Abdullah Alahmadi, Maryam Ahmed, Samah F. Faqeeh, Dalal Alahmadi, Abdulaziz A. Qurashi, Fahad H. Alhazmi, Rakan Mohammed Alrehaili and Abdulrahman Khalil Almughathawi

Gastroenterol. Insights 2024, 15(3), 588-598; https://doi.org/10.3390/gastroent15030043 - 4 Jul 2024

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Abstract

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) ranges from hepatic steatosis to nonalcoholic steatohepatitis and may lead to liver cirrhosis. This study aimed to assess the feasibility of numerical grading MASLD using noncontrast computed tomography (NCCT). Methods: In a retrospective study of 166 [...] Read more.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) ranges from hepatic steatosis to nonalcoholic steatohepatitis and may lead to liver cirrhosis. This study aimed to assess the feasibility of numerical grading MASLD using noncontrast computed tomography (NCCT). Methods: In a retrospective study of 166 patients diagnosed with MASLD between June 2020 and January 2024, MASLD was graded by ultrasonography, and liver density was measured on NCCT. The MASLD grades and NCCT densities were compared. Results: The MASLD grades were distributed as follows: grade 0 (n = 79, 47.6%), grade 2 (n = 48, 28.9%), grade 1 (n = 25, 15.1%), and grade 3 (n = 14, 8.4%). The mean liver density was 57.75 Hounsfield units (HU) ± 6.18 (range: 48.9–78.2), 51.1 HU ± 4.7 (range: 41.4–59.7), 39.3 ± 6.4 (range: 21.4–48.9), and 22.87 ± 7.5 (range: 12–36.4) in the grade 0, grade 1, grade 2, and grade 3 patients, respectively. An analysis of variance test showed significant variance in the distribution of mean liver density in the different MASLD grades (p < 0.001). Conclusions: After ultrasonography diagnosis of MASLD, NCCT offers an objective, numerical, and calculable method for MASLD grading that is available for radiologists, radiologic technologists, and interested physicians away from experience dependence. NCCT determined that grade 2 had a specific density from 36.4 to 41.4 HU that significantly overlapped with grade 1 (41.4–48.9) HU and with grade 3 (21.4–36.4 HU). Grade 1 showed a significant overlap with the normal liver (48.9–59.7 HU). Full article

(This article belongs to the Section Gastrointestinal and Hepato-Biliary Imaging)

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14 pages, 4016 KiB

Open AccessArticle

Mitigative Effect of Graphene Oxide Nanoparticles in Maintaining Gut–Liver Homeostasis against Alcohol Injury

by Hiral Aghara, Prashsti Chadha and Palash Mandal

Gastroenterol. Insights 2024, 15(3), 574-587; https://doi.org/10.3390/gastroent15030042 - 2 Jul 2024

Viewed by 319

Abstract

Alcoholic liver disease (ALD) develops when the immunotolerant environment of the liver is compromised due to excessive alcohol consumption. ALD progression involves variations in the expressions of multiple genes, resulting in liver inflammation and the development of a leaky gut. It is still [...] Read more.

Alcoholic liver disease (ALD) develops when the immunotolerant environment of the liver is compromised due to excessive alcohol consumption. ALD progression involves variations in the expressions of multiple genes, resulting in liver inflammation and the development of a leaky gut. It is still unclear which molecular mechanism is involved in ALD progression, and due to that, there are currently no FDA-approved drugs available for its treatment. In this study, the protective effects of graphene oxide (GO) nanoparticles were investigated against ethanol-induced damage in the gut–liver axis in in vitro. GO was synthesized using a modified Hummer’s method, and characterization was performed. Given the general concerns regarding nanoparticle toxicity, assessments of cell viability, lipid accumulation, DNA damage, cell death, and the generation of reactive oxygen species (ROS) were conducted using various techniques. Furthermore, the gene expressions of pro- and anti-inflammatory cytokines were determined using RT-qPCR. The findings reveal that GO promoted cell viability even against ethanol treatment. Additionally, lipid accumulation significantly decreased when cells were treated with GO alongside ethanol compared to ethanol treatment alone, with similar trends observed for other assays. A gene expression analysis indicated that GO treatment reduced the expression of proinflammatory cytokines while enhancing the expression of antioxidant genes. Moreover, GO treatment led to improvements in gut integrity and a reduction in proinflammatory cytokines in colon cells damaged by ethanol. These findings suggest that GO holds promise as a drug carrier, exhibiting no observed toxic effects. By shedding light on the protective effects of GO against ethanol-induced damage, this study contributes to the burgeoning field of nanoparticle-mediated therapy for ALD. Full article

(This article belongs to the Section Liver)

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19 pages, 2672 KiB

Open AccessReview

Exploring Gut–Brain Interaction Disorders: Mechanisms and Translational Therapies Crossing Neurology to Gastroenterology

by Georgi V. Vasilev, Dimitrina Miteva, Milena Gulinac, Lyubomir Chervenkov, Meglena Kitanova and Tsvetelina Velikova

Gastroenterol. Insights 2024, 15(3), 555-573; https://doi.org/10.3390/gastroent15030041 - 2 Jul 2024

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Abstract

The bidirectional communication network between the gut and the brain, known as the gut–brain axis, plays a crucial role in health and disease. This review explores the mechanisms underlying gut–brain interaction disorders and highlights translational therapies bridging neurology and gastroenterology. Mechanisms encompass anatomical, [...] Read more.

The bidirectional communication network between the gut and the brain, known as the gut–brain axis, plays a crucial role in health and disease. This review explores the mechanisms underlying gut–brain interaction disorders and highlights translational therapies bridging neurology and gastroenterology. Mechanisms encompass anatomical, endocrine, humoral, metabolic, and immune pathways, with the gut microbiota exerting profound influence. Clinical evidence links gut microbiota fluctuations to mood disorders, GI disruptions, and neurodevelopmental conditions, emphasizing the microbiome’s pivotal role in shaping brain–gut interactions. Pharmacological therapies such as amitriptyline and selective serotonin reuptake inhibitors modulate neurotransmitter activity, offering relief in functional gastrointestinal disorders like irritable bowel syndrome (IBS). Non-pharmacological interventions like cognitive–behavioral therapy and hypnotherapy address maladaptive thoughts and induce relaxation, alleviating gastrointestinal symptoms exacerbated by stress. Emerging therapies include gut microbiota modulation, dietary interventions, vagus nerve stimulation, and intestinal barrier modulation, offering novel approaches to manage neurological disorders via the gastrointestinal tract. Understanding and harnessing the gut–brain axis holds promise for personalized therapeutic strategies in neurogastroenterology. Full article

(This article belongs to the Section Gastrointestinal Disease)

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14 pages, 7521 KiB

Open AccessArticle

Evaluation of Immunological Response to TLR2 and α-SMA in Crohn’s Disease and Ulcerative Colitis

by Anthea Miller, Giorgia Pia Lombardo, Giuseppina Rizzo, Magdalena Kotanska, Giuseppinella Melita, Socrate Pallio, Alba Migliorato, Giuseppina Cutroneo and Simona Pergolizzi

Gastroenterol. Insights 2024, 15(3), 541-554; https://doi.org/10.3390/gastroent15030040 - 28 Jun 2024

Viewed by 359

Abstract

Inflammatory bowel diseases (IBDs) represent multifactorial chronic inflammatory conditions of the gastrointestinal tract. The main IBDs are Crohn’s disease (CD) and ulcerative colitis (UC). CD may cause perforation, stricture or transmural inflammation, which can occur discontinuously in the entire gastrointestinal tract (GIT). UC [...] Read more.

Inflammatory bowel diseases (IBDs) represent multifactorial chronic inflammatory conditions of the gastrointestinal tract. The main IBDs are Crohn’s disease (CD) and ulcerative colitis (UC). CD may cause perforation, stricture or transmural inflammation, which can occur discontinuously in the entire gastrointestinal tract (GIT). UC leads to mucosal inflammation as well as mucosal atrophy in the rectum and the colon. Innate immunity is considered the first line of defense against microbial invasion; among Toll-like receptors, TLR2 is the most important for defense against mycobacterial infection. TLR2 has been reported to have a lot of functions in infectious diseases and in other pathologies, such as chronic and acute inflammatory diseases. Alfa-Smooth Muscle Actin (α-SMA) is an important biomarker in IBDs. All myofibroblasts express α-SMA, which has been found to be upregulated in CD and UC. Paraformaldehyde-fixed intestinal tissues, from patients with CD and patients with UC, were analyzed by immunostaining for TLR2 and α-SMA. Our results showed that, in the samples obtained from UC patients with inflamed mucosa, TLR2-positive epithelial cells concentrated on the mucosal surface and scattered immune cells in the connective tissue; furthermore, numerous α-SMA-positive cells (subepithelial myofibroblasts) were detected in the lamina propria and around glands, while some myofibroblasts co-localizing with α-SMA and TLR2 could be inflammatory macrophages. In CD patients, TLR2-positive enterocytes and α-SMA-positive myofibroblasts in the lamina propria of the villus have been observed. In control samples, a low positivity to α-SMA and TLR2 was observed in subepithelial myofibroblasts and scattered immune cells of the lamina propria. These data showed the recall of α-SMA-positive myofibroblasts during the inflammatory state; in addition, TLR2 expression has been observed to change in the intestinal epithelium in IBDs, demonstrating that alterations in the innate system response may contribute to the pathogenesis of these diseases. Full article

(This article belongs to the Section Gastrointestinal Disease)

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11 pages, 1609 KiB

Open AccessArticle

The Severity of Gastrointestinal Disorders and Autistic-Like Behaviors Could Be Associated with a Selective Humoral Response to Bovine Milk Caseins: A Case Series

by Ángel F. Valenzuela-Zamora, Rocío Campos-Vega, José A. López-Diaz and Abraham Wall-Medrano

Gastroenterol. Insights 2024, 15(3), 530-540; https://doi.org/10.3390/gastroent15030039 - 26 Jun 2024

Viewed by 1042

Abstract

Severe gastrointestinal symptoms (GIS) and food hypersensitivity are tightly associated in young individuals with autism spectrum disorders (ASD). Here, we explored the relationship of GIS (gastrointestinal severity index, ROMA IV criteria, Bristol scale), ASD-like behaviors (Childhood Autism Rating Scale), and certain sociodemographic/clinical traits [...] Read more.

Severe gastrointestinal symptoms (GIS) and food hypersensitivity are tightly associated in young individuals with autism spectrum disorders (ASD). Here, we explored the relationship of GIS (gastrointestinal severity index, ROMA IV criteria, Bristol scale), ASD-like behaviors (Childhood Autism Rating Scale), and certain sociodemographic/clinical traits (epidemiological survey) with serum immunoreactivity (IgG, IgA, IgE titers) towards bovine milk caseins (BMC; by ELISA) and subfractions (by immunoblotting) in thirty-one pediatric patients (~3–15 y, 77% male) with mild-to-severe GIS and ASD-like behaviors. In total, 42%, 25%, and 23% of all participants exhibited no (IgG−/IgA−), mono (IgG+/IgA−), or dual (IgG+/IgA+) immunoreactivity to BMC, respectively; the trend was significantly associated with the severity of the GIS and ASD-like behaviors, regurgitations, and self-reported allergies (OR: 1 → (1.9–3.1) → 13.5–16.0)]. No IgE+ response to BMC was found. Dual responders were α > κ > β-casein, though nonspecific reactivity to other protein fractions was also observed. The IgA+ > IgG+ but not IgE+ response to BMC (mainly α-casein) seems to be related to the severity of GIS and ASD-like behaviors, although a larger number of ASD patients are needed to draw a causal association. Full article

(This article belongs to the Special Issue Recent Advances in the Management of Gastrointestinal Disorders)

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11 pages, 874 KiB

Open AccessArticle

Repeated Previous Transarterial Treatments Negatively Affect Survival in Patients with Hepatocellular Carcinoma Receiving Sorafenib

by Bernardo Stefanini, Luca Ielasi, Andrea Casadei-Gardini, Michele Piscopo, Raffaella Tortora, Lorenzo Lani, Tiziana Pressiani, Vito Sansone, Rodolfo Sacco, Giulia Magini, Matteo Renzulli, Francesco Giuseppe Foschi, Fabio Piscaglia, Francesco Tovoli and Alessandro Granito

Gastroenterol. Insights 2024, 15(3), 519-529; https://doi.org/10.3390/gastroent15030038 - 22 Jun 2024

Viewed by 273

Abstract

Background: Transarterial chemoembolisation (TACE) and radioembolisation (TARE) can lead to the deterioration of liver function, especially in cases of a high tumour burden, potentially lessening the benefits of subsequent systemic treatments. We aimed to verify whether a high number of previous transarterial treatments [...] Read more.

Background: Transarterial chemoembolisation (TACE) and radioembolisation (TARE) can lead to the deterioration of liver function, especially in cases of a high tumour burden, potentially lessening the benefits of subsequent systemic treatments. We aimed to verify whether a high number of previous transarterial treatments modified the outcomes of patients who received sorafenib as a frontline systemic treatment. Methods: A retrospective analysis of a large multicenter dataset containing prospectively collected data of sorafenib-treated patients was conducted. Results: Data from 696 patients were analysed, with 139 patients having received >two transarterial procedures before starting sorafenib. A propensity score matched 139 identified pairs of patients. Having received >two locoregional treatments was independently associated with a shorter survival (hazard ratio 1.325, 95% confidence interval 1.018–1.725, p = 0.039). This pattern was confirmed amongst responders to sorafenib, but not in progressors. A trend toward a higher rate of the permanent discontinuation of sorafenib due to liver failure (18.7 vs. 10.8%, p = 0.089) and a lower rate of eligibility for second-line treatments (24.5 vs. 17.3%, p = 0.184) was observed in patients who had received >two transarterial procedures. Conclusions: Repeated endovascular treatments negatively impacted the survival of HCC patients, especially sorafenib-responders. An early switch to systemic therapies should be considered in cases that are unlikely to respond. Full article

(This article belongs to the Section Liver)

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Gastroenterol. Insights, Volume 15, Issue 3 (September 2024) – 8 articles

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