Editorial


Indirect immunofluorescence on HEp-2 cell-line (HEp-2-IIF) remains the “gold standard” method for detection of antinuclear antibodies (ANA) (1). ANA is an operative definition, showing the possibility of autoantibodies (Aab) to bind nucleus and cytoplasmic antigen. One of the major examples is represent by anti-mitochondrial antibodies (AMA), which target proteins of the inner and outer mitochondrial membranes, located in the cytoplasm. In routinely lab-life the AC-21 pattern and the presence of related AMA can be confirm by commercial line-immunoblotting, ELISA, CLIA/FEIA assays and the standard IIF on rodent kidney/stomach/liver tissue sections. Several studies showed the use of other commercial assays and home made tests to detect AMA as immunoprecipitation and immunoblotting. However the use of IP or IP-WB in a routinely laboratory is difficult to apply, because of numerous cases to process and the related troubles.

The routinely lab experience also teach that commercial kits can not always detected and define specific AMA. Where find confirmation of AC-21 pattern if line-immunoblot and other routinely methods (ELISA, CLIA/FEIA assays) fail? We review AC-21 AMA-like sera from our patinets (year 2022) and purpose a revised diagnostic algorithm based on the combined use of IIF on Hep-2 cells, line immunoblot and IIF on rodent tissue as third line method. We showed that the use of IFI on rodent tissues became diriment to confirm AMAs presence, expecially when second level assay failed.

Systematic Review and Meta-Analysis


Posterior tibial nerve electrical stimulation in chronic constipation: a systematic review and meta-analysis

Mahdieh Hamedfar, Fariba Ghaderi, Hanieh Salehi Pourmehr, abbas soltani, Morteza Ghojazadeh, nafiseh vahed

Gastroenterology and Hepatology from Bed to Bench, Vol. 17 No. 1 (2024), 7 January 2024,
https://doi.org/10.22037/ghfbb.v17i1.2831

Introduction: Posterior tibial nerve electrical stimulation is a management procedure for chronic constipation. This systematic review and meta-analysis was performed to investigate the methods of application of the posterior tibial nerve electrical stimulation in patients with chronic constipation.

Methods: A comprehensive search of Ovid, PubMed, Scopus, ProQuest, Web of Science, and The Cochrane Library was conducted based on the PICO formation of the study. Two independent reviewers screened all titles, abstracts, and full texts. The selected studies' quality was assessed critically using the Joanna Briggs Institute checklists. The data synthesis was conducted using Review Manager software.

Results: Of 1016 records, 11 studies were included in this review. The results showed transcutaneous tibial nerve stimulation (TTNS) could be an effective intervention for improving constipation symptoms (SMD: -1.52, CI 95%: -2.81 to -0.22, p< 0.0001) and reducing the defecation time (SMD: -0.86, CI 95%: -1.60 to -0.13, p= 0.17). Also, subgroup analysis revealed posterior tibial nerve stimulation (PTNS) was effective in the improvement of the quality of life of patients with chronic constipation (SMD: -1.32, CI 95%: -2.05 to -0.59, p< 0.00001).

Conclusion: Posterior tibial nerve electrical stimulation as a minimally invasive method could be suggested for chronic constipation. The methods of application were different between the studies, but we could suggest TTNS may be more effective than PTNS with the least adverse effects. However, a definite standard treatment plan could not be suggested due to the various parameters and measured outcomes.

Review Article


Biguanides and Glucagon Like Peptide 1 Receptor Agonists in the Amelioration of Post Liver Transplant Weight Gain; A Scoping Review of the Mechanism of Action, Safety and Efficacy

Benjamin Mac Curtain, Luke O Brien , Omar El Sherif , Aidan Mc Cormick , Emer Carolan, John Ryan, Donal O Shea, Tom Gallagher

Gastroenterology and Hepatology from Bed to Bench, Vol. 17 No. 1 (2024), 7 January 2024,
https://doi.org/10.22037/ghfbb.v17i1.2899

Background – Weight gain post liver transplant can lead to adverse patient outcomes in the post-transplant period. Pharmacotherapy, along with other measures can be utilised in order to reduce the burden and occurrence of weight gain in this population.

Aims - We explored the mechanism of action, safety and efficacy of these medications, more specifically GLP-1 receptor agonists and Metformin, with a focus on liver transplant patients.

Methods – This scoping review was conducted in line with the scoping review structure as outlined by the PRISMA guidelines.  

Results – Metformin and GLP-1 receptor agonists have been observed to be safe and effective in liver transplant patients. Experimental models have found liver centric mechanisms of weight loss in this drug cohort.  

Conclusions – There is a paucity of evidence in relation to the use of antihyperglycemics in a post-transplant population for weight loss purposes, however, some small studies have shown strong safety and efficacy data. The evidence in relation to using these medications in patients with metabolic syndrome for weight loss warrants further study in a transplant population.  

Original Article


The Anti-inflammatory Effects of Antidepressants on Ulcerative Colitis

Hajar Khazraei , Seyedeh Azra Shamsdin

Gastroenterology and Hepatology from Bed to Bench, Vol. 17 No. 1 (2024), 7 January 2024,
https://doi.org/10.22037/ghfbb.v17i1.2850

Abstract

Background & purpose: The incidence of depression with ulcerative colitis in patients has led to the use of antidepressants in their treatment. In addition to the antidepressant effect of these drugs, anti-inflammatory effects have also been reported. Clomipramine (tricyclic antidepressant), Risperidone (a typical antidepressant), and Escitalopram (selective serotonin reuptake inhibitor antidepressant) might be good candidates for investigating the anti-colitis activity.

Methods: In this study, 36 rats were used 2 ml of 3% acetic acid solution rectally to show the colitis. Then, Clomipramine (25 mg/kg), Escitalopram (10mg/kg), Prednisolone (5 mg/kg), Risperidone (2mg/kg), and normal saline as the control were administered orally for six days. The levels of Tumor Necrosis factor-alpha (TNF-α), Interleukin-6 (IL-6), and myeloperoxidase (MPO) were measured by Enzyme-linked immune sorbent assay (ELISA), and changes in tissue pathology were investigated.

Results: IL-6 level was significantly reduced after the administration of clomipramine and Prednisolone (p=0.025). Risperidone has significantly reduced MPO activity in colonic tissue (P=0.006). We did find no statistically decrease in MPO activity and TNF-α and IL-6 levels after consumption of Escitalopram (p>0.05).

Conclusion: Clomipramine showed the best anti-inflammatory effect in comparison with Escitalopram and Risperidone. Therefore, clomipramine showed the best relieving effect on inflammation of ulcerative colitis in patients.

 

Aim: We aim to investigate the relation of these two circular RNAs with clinicopathological data of colorectal cancer patients.

Background: Circular RNAs (circRNAs) are implicated in the progression and development of Colorectal cancer (CRC). CircRNAs have been recognized as diagnostic and prognostic biomarkers and opening up a new window in order to comprehend the molecular basis of CRC. Given the significance of circRNAs and the G protein subunit b1 (GNB1) gene in malignancies, the goal of the current investigation was to determine the expression levels of GNB1 derivative circular RNAs circGNB1 (hsa_circ_0009361 and hsa_circ_0009362) in CRC and nearby control tissues.

Methods: The expression levels of the GNB1 derivative circular RNAs hsa_circ_0009361 and hsa_circ_0009362 in 45 CRC tissues and nearby control tissues were evaluated using the quantitative real-time PCR (qRT-PCR) method. All other data analyzed by GraphPad Prism software (La Jolla, CA).

 Furthermore, we analyzed the diagnostic power of the mentioned circRNAs by plotting the receiver operating characteristic (ROC) curve. The association between the expression levels of hsa_circ_0009361 and hsa_circ_0009362 was evaluated using correlation analysis.

Result: Our results revealed that the expression levels of hsa_circ_0009361 and hsa_circ_0009362 were significantly down-regulated in CRC tissues compared to the adjacent control group. Analysis of patients’clinicopathological features shows that, expressions hsa_circ_0009361 and hsa_circ_0009362 were differently related with lymph vascular invasion (P < 0.001). ROC curve results have shown that these circRNAs are good candidate diagnostic biomarkers in CRCs. Pearson’s correlation test showed a positive correlation between hsa_circ_0009361 and hsa_circ_0009362 expression levels (P < 0.0001).

Conclusion: These results revealed that hsa_circ_0009361 and hsa_circ_0009362 expression levels may be used as possible diagnostic biomarkers for CRC.

Keywords: Circular RNA · hsa_circ_0009361 · hsa_circ_0009362. Colorectal cancer

The investigation of death-inducing potency of a recombinant Adenovector expressing Mda-7-tlyp-1 on different cancer cell lines

Fatemeh Vatanparast, Rozita Ghojoghi, Maryam Kadkhodazadeh, Fatemeh Nekooei, Jamal Sarvari, Mahroo Rastegari, Kazem Baesi, Fatemeh Jamali, Zahra Farmani, Seyed Younes Hosseini

Gastroenterology and Hepatology from Bed to Bench, Vol. 17 No. 1 (2024), 7 January 2024,
https://doi.org/10.22037/ghfbb.v17i1.2779

Abstract

Introduction: Mda-7 could complement cancer gene therapy and tethering tumor-homing peptides (THPs) to the structure might improve the therapeutic efficacy. Herein, an Adenovector expressing Mda7-tLyp1 (Ad-Mda7-tLyp1) was prepared and evaluated on breast, liver and gastric cancer cell lines.

Materials and Methods: After preparation of recombinant Ad-Mda7-tLyp1 and Ad-Mda7, the expression of recombinant proteins was analyzed by ELISA. Adenovectors were transduced (MOI=2-5) into Hep-G2, MCF7, MKN-45, and normal fibroblast, then tumor killing effect was measured by cytopathic effect monitoring, MTT viability test, BAX gene expression analysis, and Caspase3/7 colorimetric assay.

Results: The ELSA revealed a sustained level of recombinant proteins secretion following vector transduction. The CPE and viability test showed that Ad-Mda7 and Ad-Mda7-tLyp1 have a significant killing effect on MCF-7, Hep-G2 and MKN-45 compared to fibroblast cell. The BAX expression analysis and caspase 3/7 activity was also showed a significant increase(P<0.05) in apoptosis level following Adenovector transduction into cancer but not fibroblast cells.

Conclusion: The newly constructed Ad-Mda-tlyp1 showed a suitable tumor cell killing activity and either enough specificity.

Small Fiber Neuropathy in Irritable Bowel Syndrome

Pouria Motaghi, Iman Adibi, Peyman Adibi, Majid Ghasemi

Gastroenterology and Hepatology from Bed to Bench, Vol. 17 No. 1 (2024), 7 January 2024,
https://doi.org/10.22037/ghfbb.v17i1.2827

Aim: In this study, we intend to evaluate the occurrence of small fiber neuropathy in patients with irritable bowel syndrome (IBS).

Background: Small fiber neuropathy (SFN) is a sensory neuropathy that results from the degeneration of small Aδ and unmyelinated C fibers. SFN manifests positive symptoms, such as tingling, burning, prickling, and aching, and negative symptoms, including numbness, tightness, and coldness. The SFN coexistence with other comorbidities (e.g., fibromyalgia, inflammatory bowel disease, celiac disease) has been reported in previous studies.

Patients and Methods: We conducted a cross-sectional study to assess the coexistence of SFN and IBS. Forty-two IBS patients and forty-three healthy individuals were asked to fill out the Michigan Neuropathy Screening Instrument (MNSI) questionnaire. Results greater than three (>3) were considered positive. Participants with positive MNSI questionnaire results were examined for any neuropathy signs according to the Utah Early Neuropathy Scale (UENS) examination. The participants with positive results for the questionnaire and examination were checked for the sural and the superficial peroneal nerve conduction study (NCS). Normal NCS represented intact large fibers and the diagnosis of SFN.

Results: Ten participants, 7 (16.7 %) in the IBS group and 3 (6.9 %) in the healthy group, had positive results for the questionnaire. Four participants were positive for the examination, with normal NCS, and they were classified as SFN positive participants. All four SFN diagnoses were from the IBS group. No one in the healthy group was diagnosed with SFN. We could find a significant statistical difference (p < 0.05) between the IBS group and the healthy group in terms of the prevalence of SFN diagnosis.

Conclusion: The correlation between SFN and IBS suggests the possibility of a generalized neuropathy syndrome characterized by widespread neuronal impairment. Thus, any peripheral neuropathy symptom in IBS patients (and potentially other chronic pain disorders) should be evaluated for SFN since timely diagnosis and proper treatment result in a better quality of life for the patients.

Hypolipidemic and hepatoprotective effects of corn silk extract in nicotine-administered male mice

Anahita Mohammadi, Ali Akbar Oroojan, Mehdi Hashemi, Seyedeh Mahsa Poormoosavi, Mojtaba Dolatshahi, Fatemeh Golshokouh

Gastroenterology and Hepatology from Bed to Bench, Vol. 17 No. 1 (2024), 7 January 2024,
https://doi.org/10.22037/ghfbb.v17i1.2806

Aim: This study aims to investigate the hypolipidemic and hepatoprotective effects of corn silk extract in nicotine-administered male mice.

Background: Nicotine can induce pathophysiological effects in the liver tissue through oxidative stress and damage cells. Corn silk can improve liver function with its antioxidant effects.

Methods: In this experimental study, 30 male NMRI mice (25-30gr) were divided into 5 groups: controls, nicotine 2.5mg/kg, nicotine+aqueous extract of corn silk 400mg/kg, and nicotine+methanolic extract of corn silk 400 mg/kg for 1 month. One day after the last administration of nicotine and extracts, the serum and supernatant samples of halogenated liver were for antioxidant and biochemical variables measurement.

Results: There was no significant difference in the body weight of different groups. Liver weight and GSH decreased in the nicotine group compared to the control group (P<0.05). Triglycerides, total cholesterol, HDL-C, LDL-C, LDL-C/HDL-C, liver enzymes, and MDA increased in the nicotine group compared to the control group (P<0.05). Also, the expansion of sinusoids, the presence of inflammatory cells, and necrosis of liver cells were observed in the nicotine group compared to the control group. The use of aqueous and methanolic extracts of corn silk in mice receiving nicotine led to the improvement of mentioned variables changes (P<0.05).

Conclusions: The results of this study showed that the use of nicotine can lead to the induction of hepatotoxicity and increase the risk of cardiovascular diseases and the use of aqueous and methanolic extracts of corn silk improved them through its antioxidant activity.

The self-care application for patients with liver cirrhosis: An intervention study

Zahra Asadzadeh, Elham Maserat, Leila Alizadeh, Zeinab Mohammadzadeh

Gastroenterology and Hepatology from Bed to Bench, Vol. 17 No. 1 (2024), 7 January 2024,
https://doi.org/10.22037/ghfbb.v17i1.2846

Background: Liver cirrhosis is a progressive and chronic disease which, if left untreated, leads to liver cancer and finally the death of the patient. Mobile phones have high potential in treatment and overcome the limitations of current treatment methods. Therefore, the present study was conducted with the aim of designing and evaluating a mobile-based self-care application for patients with liver cirrhosis.

Methodology: The current research was conducted in six phase including: determining the minimum set of data for self-care application for patients with liver cirrhosis, determining the validity of information elements of self-care application, designing a conceptual and logical model and determining the programming language and necessary infrastructure based on it, designing user-oriented and knowledge-oriented self-care application, evaluation of the prototype usability in a laboratory environment by technical experts, evaluation of the application usability in a real environment by patients with liver cirrhosis. The evaluation of designed application was done in the real environment by 30 patients and through the QUIS questionnaire.

Result: The clinical experts participating in this research recognized the majority of recommended data elements as necessary. This application has capabilities such as calculating the patient's MELD score (Model for End-Stage Liver Disease), medication reminder, location in case of emergency and conversation with physician. The results showed that the patients evaluated the application with a score of 7.94 (out of a total of 9 points) at a good level.  

Conclusion:

The self-care application, according to the results, can help patients with liver cirrhosis and their families to have access to the necessary information related to the special care of the patient at any time and place. And also can help better manage the patient's life and improve the quality of life and patient monitoring. The self-care applications can be effective in managing chronic diseases by reducing the burden of referrals and costs.

Introducing Matrix Metallopeptidase 9 (MMP9) as a Critical Protein in Liver Ischemia/Reperfusion Injury

Babak Arjmand , Mahmood Khodadost, Somayeh Jahani Sherafat, Mostafa Rezaei –Tavirani, Nayebali Ahmadi, Sina Rezaei Tavirani

Gastroenterology and Hepatology from Bed to Bench, Vol. 17 No. 1 (2024), 7 January 2024,
https://doi.org/10.22037/ghfbb.v17i1.2555

Background: Liver transplantation (LT) is a known treatment in the liver diseases which are faced to mortality. LT is a complex and several risks including liver ischemia/reperfusion (I/R) injury effect its success. Improvement LT requires detection of its molecular mechanism. Experiments revealed that high throughput methods such as proteomics in combination with bioinformatics are useful tools to analyze molecular mechanism of diseases.

Aim: Introducing the key proteins which are involve in liver I/R injury via protein-protein interaction (PPI) analysis is aim of this study.

Methods: The differentially expressed proteins (DEPs) involved in liver I/R injury were extracted from literature. The queried DEPs plus 100 first neighbors were included a network via STRING database by cytoscape software. Degree, betweenness centrality, closeness centrality, and stress were considered to determine the central nodes. The queried DEPs were assessed via action map analysis by CluePedia application of cytoscape software. The key proteins were identified via comparison of network analysis and action map evaluation results.

Results: Six proteins including ALB, INS, GAPDH, CAT, IL6, and TNF among the added first neighbors were determined as central first neighbors. MPO, CRP, MMP9, and HMOX1 were selected as central DEPs among the queried proteins. Action map analysis confirmed PPI findings. The final evaluation revealed that MMP9 in combination with CRP and HMOX1 play critical role in liver I/R injury.

Conclusion: Significant role of MMP9 in liver I/R injury was detected in this project. Two central proteins (CRP and HMOX1) showed regulatory effect on MMP9. CRP activates MMP9 while HMXO1 down regulated it.

Case Report


Rare and challenging case of extrahepatic costal metastases from an unknown primary Hepatocellular carcinoma

CYNTHIA MEDLIJ, Christophe-Karl SOUAID, Olivier MARTY

Gastroenterology and Hepatology from Bed to Bench, Vol. 17 No. 1 (2024), 7 January 2024,
https://doi.org/10.22037/ghfbb.v17i1.2812

Hepatocellular carcinoma (HCC) typically presents with primary hepatic mass. Although, on rare occasions, the initial presentation can be exclusively related to extrahepatic metastases. The most common sites of extrahepatic metastatic HCC are the lungs, lymph nodes, bones, and adrenal glands. While, bone metastases are generally accompanied by multiple metastatic spreads elsewhere in the body or previously diagnosed HCC, cases of solitary bone metastases from an unknown primary HCC have been reported.

In fact,  three rare entities of HCC have bee reported in the literature which are ; the ectopic hepatocellular carcinoma also known as metastases from an unknown primary HCC, the infiltrative type of hepatocellular carcinoma with a very challenging radiologic diagnosis and the very rare spontaneous regression of primary HCC liver lesion without medical intervention.

In this article, we present a case of extrahepatic costal metastases of hepatocellular carcinoma, which was diagnosed through a bone biopsy, with no focal lesion on liver imaging including ultrasound, multiphase MRI, and CT Scan except for the presence of a portal vein thrombosis. Unfortunately we weren’t be able to perform a liver biopsy in order to eliminate an infiltrative type of hepatocellular carcinoma with a unique radiologic sign of portal vein thrombosis.

Notably, in this case, the patient presented with a high alpha-fetoprotein (AFP) level, which highlights the role of AFP in HCC diagnosis.

Abdominal pain in a young lady with Inverted Meckel’s diverticulum: a case report

Seyed Mohammad Reza Nejatollahi, Keihan Mostafavi, Fariba Ghorbani

Gastroenterology and Hepatology from Bed to Bench, Vol. 17 No. 1 (2024), 7 January 2024,
https://doi.org/10.22037/ghfbb.v17i1.2815

Meckel diverticulum is the most common congenital anomaly of the gastrointestinal tract which is located in the small bowel within 2 feet of the ileocecal valve. However, an inverted Meckel's diverticulum is a rare disorder that seems to be caused by abnormal peristalsis in that region. This article demonstrates signs, symptoms and possible clinical presentations using CARE guideline in a case of inverted Meckel's diverticulum and review other possible features lastly, definitive treatment, results and case follow-up was shown to refresh and raise surgeons' awareness of this rare disorder.