Torabi S, Mohammadi Y, Hoseini MS
… +3 more, Rezaei A, Mohammadi A, Bahreini E
Arab J Gastroenterol
· 2025 Nov · PMID 41198499
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INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD), the most common chronic liver disease, is characterized by lipid droplet (LD) accumulation in more than 5% of hepatocytes. This study aimed to investigate apoptosi...INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD), the most common chronic liver disease, is characterized by lipid droplet (LD) accumulation in more than 5% of hepatocytes. This study aimed to investigate apoptosis in HepG2 cells exposed to palmitate, oleate, and a combination of palmitate and oleate. METHODS: The effective concentrations of palmitic and oleic acids were determined using the MTT assay. Subsequently, an optimal combined dose of these fatty acids was selected to induce LD formation. Intracellular LD accumulation following treatment with different concentrations of palmitate and oleate was assessed qualitatively and semi-quantitatively using Oil Red O staining and light microscopy. Expression levels of apoptosis-related genes (p53, Bax, FasL, and Bcl-2) were quantified using real-time PCR. RESULTS: Palmitate treatment markedly reduced cell density and enhanced LD accumulation, whereas oleate exhibited milder effects. The palmitate-oleate (P&O) combination induced greater LD accumulation than oleate alone but was less cytotoxic than palmitate. At the molecular level, pro-apoptotic genes (P53, Bax, and FasL) were upregulated in all treated groups, with the highest expression in the P&O group. Conversely, the anti-apoptotic gene Bcl-2 was significantly downregulated in palmitate-treated cells. CONCLUSION: Saturated and unsaturated fatty acids exert distinct yet interconnected effects on lipid homeostasis and hepatocyte viability. Maintaining their proper balance may be critical in preventing liver injury. Further studies are warranted to elucidate the underlying mechanisms.
Arab J Gastroenterol
· 2026 Feb · PMID 41198498
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BACKGROUND: Licoricidin is a prenylated isoflavone isolated from Glycyrrhiza uralensis Fisch, and its biological activities and pharmacological properties have been reported in recent years. This study comprehensively ex...BACKGROUND: Licoricidin is a prenylated isoflavone isolated from Glycyrrhiza uralensis Fisch, and its biological activities and pharmacological properties have been reported in recent years. This study comprehensively explored the licoricidin's effect on hepatocellular carcinoma (HCC) and elucidated its underlying mechanism. METHODS: HCC Hep3B and Huh-7 cells were treated with licoricidin at various concentrations. The experimental methods in vitro, including CCK-8, colony formation, EdU, flow cytometry, wound healing, and transwell were performed to evaluate the licoricidin's effect on HCC cell proliferation, apoptosis, migration, and invasion. The antitumor and anti-metastasis activities of licoricidin were validated using a Hep3B xenograft model and a metastasis model. Western blot or RT-qPCR was used to measure the levels of apoptosis-, epithelial-mesenchymal transition-, and PI3K/AKT-related proteins. RESULTS: The results indicated that the antiproliferation effect of licoricidin in HCC was related to cell cycle arrest (S phase) and apoptosis induction. Licoricidin upregulated Bax and cleaved caspase3/9 expression and downregulated Bcl-2 expression in cancer cells. In a subcutaneous xenograft model, licoricidin treatment suppressed the growth of tumor. Nontoxic concentrations of licoricidin reduced the migration and invasion abilities of HCC cells. Licoricidin downregulated N-cadherin and vimentin expression, while upregulating E-cadherin expression. Licoricidin treatment reduced the number of metastatic lung nodules in a metastasis model. Inhibition of PI3K/AKT signaling might be a potential mechanism behind the licoricidin's anticancer effect. CONCLUSION: Overall, licoricidin suppresses growth and metastasis of HCC by targeting. PI3K/AKT signaling, suggesting that licoricidin might be a promising candidate for HCC treatment.
Arab J Gastroenterol
· 2025 Nov · PMID 41047283
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BACKGROUND AND STUDY AIMS: To explore the association between thyroid function and liver fibrosis using the data from the NHANES database. PATIENTS AND METHODS: The data of 5959 participants and 34 variables were obtaine...BACKGROUND AND STUDY AIMS: To explore the association between thyroid function and liver fibrosis using the data from the NHANES database. PATIENTS AND METHODS: The data of 5959 participants and 34 variables were obtained. Fibrosis-4 (FIB-4) score was used to assess the liver fibrosis level. LASSO regression analysis was conducted to identify the important thyroid function related indicators and other variables. Logistic and linear regression analyses were used to explore the association between key indicators and FIB-4 score, and their association was then verified by RCS and GAM analyses. The stability of their association was evaluated by trend regression and interaction effect analyses. RESULTS: There were 4652 and 1307 participants in low and high FIB-4 score groups, respectively. LASSO analysis initially identified 17 important variables, of which 4 thyroid indicators were contained including total T3, FT4, TSH, and TT4RI (an index for reflecting sensitivity to thyroid hormones). Of them, TSH and TT4RI showed significant association with liver fibrosis level when FIB-4 was set as categorical (fully adjusted OR = 1.048 [95 %CI: 1.026, 1.077], P < 0.001; OR = 1.007 [95 %CI: 1.004, 1.011], P < 0.001) or continuous variable (fully adjusted β = 0.010 [95 %CI: 0.004, 0.015], P = 0.001; β = 0.002 [95 %CI: 0.001, 0.003], P < 0.001). RCS and GAM analyses further supported their association (all fully adjusted P < 0.05). However, fully adjusted trend regression analysis indicated the more stable association of TT4RI with liver fibrosis in a positive relationship (OR = 1.079 [95 %CI: 1.013, 1.150], P = 0.018; β = 0.019 [95 %CI: 0.004, 0.034], P = 0.011). We further found that age, sleep disorder, sodium level, and lymphocyte number had interaction effect with TT4RI (all P for interaction effect < 0.05). CONCLUSIONS: The sensitivity to thyroid hormones was significantly related to the liver fibrosis, which was more valuable than the common thyroid profile.
Abu Sneineh A, Haj Ali S, Alani MA
… +7 more, Al Karmi J, Al Karmi F, Al-Wandawi MF, Al Bdour S, Agraib L, Ali RM, Ahram M
Arab J Gastroenterol
· 2025 Nov · PMID 40993033
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BACKGROUND AND STUDY AIMS: Noninvasive biomarkers are needed to monitor disease activity in inflammatory bowel disease, as current methods-including blood tests, endoscopy, imaging, and fecal calprotectin-are invasive, c...BACKGROUND AND STUDY AIMS: Noninvasive biomarkers are needed to monitor disease activity in inflammatory bowel disease, as current methods-including blood tests, endoscopy, imaging, and fecal calprotectin-are invasive, costly, or burdensome. This study explored salivary calprotectin as a potential biomarker for Crohn's disease activity. PATIENTS AND METHODS: This was a cross-sectional exploratory study. Unstimulated saliva was collected from patients with an established diagnosis of Crohn's disease and matched healthy controls. Disease activity was determined via the Crohn's disease Activity Index. Salivary calprotectin was measured in 20 μl saliva samples using enzyme-linked immunosorbent assay. RESULTS: Samples were collected from 42 patients with Crohn's disease (mean age 36.3 ± 14.2 years, 52.4 % male) and 41 age-matched healthy controls (mean age 38 ± 13.4 years, 58.5 % male). For patients with Crohn's disease, the median salivary calprotectin level was 0.08 (IQR 0.05-0.14) ug/ml compared to 0.06 (IQR 0.03-0.13) ug/ml in healthy controls (p = 0.161). Among patients with Crohn's disease, levels were similar in remission (0.10, IQR 0.05-0.15 μg/mL) and active disease (0.07, IQR 0.03-0.10 μg/mL; p = 0.091). No correlation was observed between salivary calprotectin and Crohn's disease activity index scores (Spearman's r = -0.136, p = 0.392). CONCLUSIONS: Salivary calprotectin did not distinguish patients with Crohn's disease from healthy controls or correlate with disease activity. While noninvasive, it does not appear to be a clinically useful biomarker for monitoring Crohn's disease. Further research may clarify its role in inflammatory bowel disease or identify more promising biomarkers.
Arab J Gastroenterol
· 2025 Nov · PMID 40987697
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BACKGROUND AND STUDY AIMS: Irritable bowel syndrome (IBS) is a common bowel dysfunction disorder. Endoplasmic reticulum (ER) stress plays a key role in the pathogenesis of several gastrointestinal diseases. This study in...BACKGROUND AND STUDY AIMS: Irritable bowel syndrome (IBS) is a common bowel dysfunction disorder. Endoplasmic reticulum (ER) stress plays a key role in the pathogenesis of several gastrointestinal diseases. This study investigated important ER stress-related genes (ERGs) and their mechanisms of action in IBS. MATERIAL AND METHODS: IBS and ERGs data were retrieved from public databases. Differential expression analysis, Venn analysis, and three machine learning algorithms, the most important ERGs in IBS were selected. A nomogram model was then constructed for the clinical predictions based on optimal ERGs. Finally, an LPS-induced Caco-2 cell line was established to simulate intestinal barrier damage and validate the expression of key genes and their underlying mechanisms. RESULTS: Six key ERGs (EGFR, MET, INSR, RETREG1, MCL1, and BSG) were selected to construct the nomogram model, which showed promising clinical predictive performance. These six genes were significantly correlated with immune response and ER stress-related pathways, such as oxidative phosphorylation. In vitro cell experiments have demonstrated damaged barrier function and ER stress activation in IBS, manifesting as lower transepithelial resistance, higher cell permeability, higher levels of inflammatory cytokines, and higher levels of ER proteins in LPS-induced cells. Furthermore, MET expression was significantly increased in the LPS group, whereas EGFR, INSR, RETREG1, MCL1, and BSG levels were significantly decreased in the LPS group. CONCLUSION: Our study demonstrated a six-gene nomogram model for IBS based on ER stress, which showed a strong relationship between ER stress and various diseases.
Xie P, Gong J, Gao X
… +4 more, Xu C, Chen J, Shen Y, Liu K
Arab J Gastroenterol
· 2025 Nov · PMID 40983559
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BACKGROUND AND STUDY AIMS: To investigate the computed tomography (CT) and clinical findings of ceftriaxone (CTRX)‑associated gallbladder pseudolithiasis (CGPL). PATIENTS AND METHODS: The CT images and clinical data of 8...BACKGROUND AND STUDY AIMS: To investigate the computed tomography (CT) and clinical findings of ceftriaxone (CTRX)‑associated gallbladder pseudolithiasis (CGPL). PATIENTS AND METHODS: The CT images and clinical data of 85 patients with a history of CTRX treatment from January 2023 to September 2023 were retrospectively analyzed. RESULTS: CGPL was found in 32 of the 85 patients. CGPLs manifested as a sludge pattern in 4 patients, a nodular pattern in 9 patients, and a mud-like pattern in 19 patients. All 4 patients with existing gallbladder lithiasis were found to have CGPL after CTRX treatment. CGPL appeared on the 6th day follow-up CT at the earliest and disappeared on the 30th day follow-up CT at the earliest, CGPL completely disappeared in 12 patients. The total bilirubin level, direct bilirubin level, and albumin/globulin ratio in the patients with CGPL were significantly lower than those in the patients without CGPL; the triglyceride, β2-microglobulin level in the patients with CGPL were significantly higher than those in the patients without CGPL. The dosage and total dose of CTRX up to the first follow-up CT (TD-FFCT) in patients with CGPL were significantly higher than those in patients without CGPL. CONCLUSION: The most common type of CGPL can be a mud-like pattern, and CGPLs can appear and disappear on the 6th and 30th day follow-up CT. The dosage and TD-FFCT are risk factors for CGPL, as well as existing gallbladder lithiasis. Total bilirubin level, direct bilirubin level, the albumin/globulin ratio, triglyceride level, β2-microglobulin level may have the evaluative value for the formation of CGPL.
Arab J Gastroenterol
· 2025 Nov · PMID 40976736
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BACKGROUND AND STUDY AIMS: Helicobacter pylori (H. pylori) infections are notably difficult to eradicate due to high antibiotic resistance and frequent reinfection. This study evaluates the effectiveness of combining ora...BACKGROUND AND STUDY AIMS: Helicobacter pylori (H. pylori) infections are notably difficult to eradicate due to high antibiotic resistance and frequent reinfection. This study evaluates the effectiveness of combining oral and gastric treatments with synchronized family therapy compared to standard therapy for H. pylori management. PATIENTS AND METHODS: Conducted at Cangshan Hospital of the 900th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army, the study included 180 patients divided into three groups: standard triple therapy (Group A), triple therapy plus oral treatment (Group B), and triple therapy with oral treatment and synchronized family therapy (Group C). Eradication and recurrence were measured at 3 and 6 months using stool antigen tests and 14C-urea breath tests. RESULTS: Initial eradication rates were similar across the three groups. By 3 months, eradication rates reached 76.7 % in Group A, 86.7 % in Group B, and 93.3 % in Group C. At 6 months, these rates were 61.7 %, 66.7 %, and 90 %, respectively. Concurrently, recurrence rates at 6 months climbed to 33.9 % and 29.8 % in Groups A and B, respectively, but remained low at 5.3 % in Group C. CONCLUSION: The addition of synchronized family therapy significantly enhances long-term eradication and reduces recurrence rates, suggesting its potential for incorporation into standard H. pylori treatment protocols.
Arab J Gastroenterol
· 2025 Nov · PMID 40976735
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BACKGROUND AND STUDY AIMS: Glutamine metabolism (GM) plays an instrumental role in the occurrence and progression of tumors. However, the characteristics of glutamine metabolism-related genes (GMRGs) in colon adenocarcin...BACKGROUND AND STUDY AIMS: Glutamine metabolism (GM) plays an instrumental role in the occurrence and progression of tumors. However, the characteristics of glutamine metabolism-related genes (GMRGs) in colon adenocarcinoma (COAD) have not been elucidated. This project aims to dig out the role of GMRGs in COAD molecular subtypes, prognosis, and tumor microenvironment (TME) to proffer a scientific foundation for the evaluation of COAD prognosis and mechanism research. MATERIAL AND METHODS: Disease data of COAD (including clinical information and gene expression data) and GMRG data were collected from The Cancer Genome Atlas (TCGA)-COAD. GMRGs in COAD were obtained through differential analysis, cluster analysis, protein-protein interaction (PPI) network analysis, and regression analysis for setting up a prognostic model. Disease information was collected from GSE29621 to validate the model. Differences in immunotherapy response and drug sensitivity among high-Riskscore (HR) and low-Riskscore (LR) groups were evaluated. RESULTS: 45 GMRGs associated with COAD survival rate were identified through univariate analysis. Cluster and survival analyses revealed that these genes could cluster the COAD population into two clusters with great survival differences. A risk model with 10 feature genes was established through regression analysis. Prediction of immunotherapy sensitivity uncovered that the LR group was more sensitive to immunotherapy. CONCLUSION: In summary, this project set up a reliable prognostic risk model with GMRGs, which can proffer a feasible basis for the study of prognosis and related mechanisms in COAD.
Arab J Gastroenterol
· 2025 Nov · PMID 40976734
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It is known that the presence of associated anomalies has become one of the most critical prognostic factor for infants born with oesophageal atresia (OA). Associated VACTERAL group of abnormalities are common, but other...It is known that the presence of associated anomalies has become one of the most critical prognostic factor for infants born with oesophageal atresia (OA). Associated VACTERAL group of abnormalities are common, but other associations are rare. Anomalies of the hepatobiliary system are even more rare among other groups. There are only a few such cases in the literature including adults and paediatric population. We describe the findings and management of one infant born with OA with tracheoesophageal fistula (TEF) and Ano rectal malformation (ARM), who was later shown to have features of obstructive jaundice. The biliary pathology was due to a preoperative diagnosis of Type 1c choledochal cyst, but in reality it was associated with an aberrant form of biliary drainage in the form of cholecystohepatic duct (CCHD). In the English literature, there are only four reported cases of cholecystohepatic duct (CCHD) in children associated with complex congenital anomalies [1-3]. The association of these multiple complex congenital anomalies with aberrant biliary duct is a rare feature. Here, in this case, this aberrant cholecystohepatic duct is the only drainage pathway of bile from liver into gallbladder.
Arab J Gastroenterol
· 2025 Nov · PMID 40976733
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Primary malignant melanoma of the esophagus (PMME) is an extremely rare malignant tumor. Primary amelanotic malignant melanoma is a subtype of PMME which shows no pigmentation under esophagogastroduodenoscopy (EGD). A la...Primary malignant melanoma of the esophagus (PMME) is an extremely rare malignant tumor. Primary amelanotic malignant melanoma is a subtype of PMME which shows no pigmentation under esophagogastroduodenoscopy (EGD). A lack of understanding of this disease makes it susceptible to misdiagnosis and limits its treatment options. Here, we reported a case which misdiagnosed as esophageal polyps with malignant transformation or esophageal cancer when observed on gastroscopy examination, while proved as primary amelanotic malignant melanoma by immunohistochemistry in our department. The aim of this study is to draw the attention of physicians by describing a case of primary amelanotic malignant melanoma and to aid in the diagnosis of this disease in the future.
Erdem O, Erdem SK, Yıldız A
… +3 more, Çakıt H, Canbey C, Özkan ÖF
Arab J Gastroenterol
· 2025 Nov · PMID 40912938
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BACKGROUND: Postoperative peritoneal adhesions (PPA) develop in up to 90% of intraabdominal surgeries and are a major cause of small bowel obstruction, leading to readmissions and morbidity. However, no effective pharmac...BACKGROUND: Postoperative peritoneal adhesions (PPA) develop in up to 90% of intraabdominal surgeries and are a major cause of small bowel obstruction, leading to readmissions and morbidity. However, no effective pharmacologic strategy currently exists for PPA prevention. Pirfenidone and Nintedanib are oral antifibrotics approved for idiopathic pulmonary fibrosis, with emerging data on their effects in cardiac and hepatic fibrosis. This study aimed to compare their efficacy in preventing PPA via intraperitoneal (IP) administration in an experimental model. METHODS: Twenty-eight rats were randomized into four groups of 7: Pirfenidone (P), Nintedanib (N), combination (P + N), and saline control (C). Adhesions were induced via cecal abrasion. On postoperative day 7, macroscopic fibrosis scores (MFS), affected regions, histopathology, and TGF-β1 expression were evaluated. RESULTS: Group P had significantly lower MFS than Group N (P < 0.001) and showed a reduction trend vs. control. TGF-β1 HScore was significantly lower in Group P vs. Group N (P = 0.002) and P + N (P = 0.014). Group N showed the highest inflammation and elevated TGF-β1 vs. control (P = 0.013). CONCLUSION: Pirfenidone appears effective in reducing PPA formation via IP administration. In contrast, Nintedanib may be unsuitable for IP use in saline, potentially due to poor solubility.
Badary HA, Ahmed R, Darweesh SK
… +7 more, Zakaria Z, Darweesh H, Ramadan H, Amin R, Zayed N, Yosry A, Abdellatif Z
Arab J Gastroenterol
· 2025 Aug · PMID 40634211
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BACKGROUND AND STUDY AIMS: Noninvasive assessment of liver fibrosis is critical for monitoring rheumatoid arthritis (RA) patients undergoing methotrexate (MTX). This study aimed to detect subclinical liver fibrosis induc...BACKGROUND AND STUDY AIMS: Noninvasive assessment of liver fibrosis is critical for monitoring rheumatoid arthritis (RA) patients undergoing methotrexate (MTX). This study aimed to detect subclinical liver fibrosis induced by MTX assessed using FIB-4, APRI, transient elastography (TE), and acoustic radiation force impulse (ARFI) elastography. PATIENTS AND METHODS: This retrospective cohort study enrolled 120 RA patients: 60 patients received MTX, and 60 received a combination of MTX and leflunomide (LEF). Liver fibrosis assessment was conducted using FIB-4, APRI, TE, and ARFI at the time of enrollment. Pretreatment FIB-4 and APRI were calculated retrospectively. RESULTS: Serum transaminase levels remained within normal ranges in both groups regardless of treatment or MTX duration. The DAS 28 score indicated that the patients were in remission at the study time. At baseline (prior to MTX administration), 114 patients (95 %) exhibited low fibrosis risk according to FIB-4, whereas 6 patients (5 %) were classified as intermediate risk. APRI indicated that 117 patients(97.5 %) exhibited non-significant fibrosis, whereas 3 (2.5 %) presented with significant fibrosis. Upon enrollment, there was a significant increase in FIB-4 scores compared to the baseline in both groups (0.56 vs. 0.72; P = 0.0002 and 0.65 vs. 0.76; P < 0.001). However, values remained within non-significant ranges. The LEF and MTX combination significantly increased APRI (0.35 vs. 0.37; P = 0.006) without reaching thresholds for significant fibrosis. TE and ARFI indicated non-significant fibrosis (F0-F1) in 116 patients (96.7) (58 per group) and moderate fibrosis (F2) in 4 patients (3.3 %). The duration of MTX treatment emerged as a significant predictor of liver fibrosis, albeit mild, as demonstrated by logistic regression analysis (OR 1.15, P = 0.008). CONCLUSION: The assessment of MTX-induced liver fibrosis in RA patients, usingTE, ARFI, and serum markers, appears to be overestimated. Transaminases did not serve as predictors of liver disease or fibrosis severity in RApatients undergoing MTXtreatment.
Gao Y, Yang H, Liu Z
… +3 more, Wang Y, Zhang X, Li Y
Arab J Gastroenterol
· 2025 Aug · PMID 40582903
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BACKGROUND AND STUDY AIMS: Diarrheal diseases among children represent a prominent global health challenge, leading to significant morbidity and mortality, especially in emerging economies. This study aims to investigate...BACKGROUND AND STUDY AIMS: Diarrheal diseases among children represent a prominent global health challenge, leading to significant morbidity and mortality, especially in emerging economies. This study aims to investigate the prevalence and trends of bacterial pathogens causing diarrhea in children. PATIENTS AND METHODS: We retrospectively conducted an analysis of outpatient and inpatient records at Children's Hospital of Soochow University, from 2016 to 2023. Only children presenting with diarrhea were included in the study. The clinical microbiology laboratory performed cultivation and identification of faecal samples, along with drug susceptibility testing on isolated Salmonella and Aeromonas species. RESULTS: A total of 2,163 cases of Salmonella, 334 cases of Aeromonas were identified from 13,662 faecal culture samples. There was a noticeable annual increase in the detection of Salmonella and Aeromonas in recent years. Samples from children with the age group of 12 to 35 months were more likely to be positive for Salmonella than those from children with other age groups, whereas those with the age group of 6 to 11 months were more prone to Aeromonas. Samples taken in the summer were most likely to be positive for Salmonella and Aeromonas. Samples from hospitalized children were considerably more likely to be positive for Salmonella than those from outpatient children. Salmonella-infected children were predominantly admitted to departments of digestion and infectious diseases, whereas Aeromonas-infected patients were spread across various clinics, especially gastroenterology. Salmonella Group B and Aeromonas punctata (caviae) were the most prevalent strains among their respective species. Notably, the resistance of Salmonella and Aeromonas to fluoroquinolone antibiotics has been escalating since 2018, with inpatients exhibiting a significantly higher rate of drug resistance compared to outpatients. CONCLUSION: The integration of bacterial identification and drug susceptibility testing is crucial for the effective prevention and management of childhood diarrhea. The use of targeted antibiotics is essential to curb the rise of drug-resistant strains and ensure effective treatment outcomes.
Arab J Gastroenterol
· 2025 Aug · PMID 40582902
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BACKGROUND AND STUDY AIMS: Sorafenib, as a novel multi-targeted oral tumor chemotherapeutic drug, has been found to exert an impact on the inhibition of cancer growth. Phosphatidylinositol-binding reticulin assembly prot...BACKGROUND AND STUDY AIMS: Sorafenib, as a novel multi-targeted oral tumor chemotherapeutic drug, has been found to exert an impact on the inhibition of cancer growth. Phosphatidylinositol-binding reticulin assembly protein interacting with mitotic regulatory factors (PIMREG) is strongly associated with oncology to drug resistance. However, how PIMREG modulates therapy tolerance to sorafenib in HCC and its potential regulatory mechanisms remain unclear. This study is abouta mechanistic approach to examine the action and mechanism of PIMREG in HCC-mediated sorafenib resistance. MATERIAL AND METHODS: The human hepatocellular carcinoma sensitive cell line Huh7 and drug-resistant cell line Huh7/SFB were used for the study, and different rates of PIMREG expansion in both cells were detected. Next, the study transfected PIMREG overexpression and interference vector into hepatoma cell line Huh7/SFB, and acted on the cells with solafenib exhibiting a concentration gradient. The growth inhibition rate and IC50 value of cells were detected by MTT method to determine the concentration and time of drug addition. Then, this study employed MTT, qRT-PCR, flow cytometry, and Western blot to assay the growth of these cells, which were induced through overexpression and disruption of PIMREG, in combination with sorafenib. The study also constructed an in vivo mouse tire sample test in order to investigate the influence of PIMREG upon the in vitro efficacy of sorafenib. In addition, the study used LY294002 inhibitors to explore the molecular mechanisms of PIMREG-mediated resistance to sorafenib in Huh7/SFB cells. RESULTS: The expression level of PIMREG in cells of the Huh7/SFB resistant strain was clearly higher than that in cells of the sensitive strain Huh7. After transfection of sh-PIMREG, the IC50 value decreased significantly, while OE-PIMREG significantly increased the IC50 value of sorafinib. Compared with the control group, inhibition of cell proliferation by sorafenib was enhanced after interference with PIMREG, while the effect of overexpression of PIMREG was on the contrary. The efficacy of sorafenib was enhanced by knockout of PIMREG in living organisms. In addition, the PI3K/AKT signal pathway was necessary for PIMREG-induced sorafenib resistance. Subsequently, PIMREG regulated sorafenib-induced inhibition of the PI3K/AKT signaling pathway, and LY294002 blocked the signal pathway to reduce PIMREG-induced resistance. CONCLUSION: All in all, an increase in HCC resistance to sorafenib via the PIMREG-mediated PI3K/AKT pathway suggests that PIMREG is a key tumor-associated gene with significant implications for sorafenib resistance in tumor cells.
Albasha Hejazi AM, Abd-ElGawad M, Gadelmawla AF
… +6 more, Abd-Elhafeez A, Abdelraheem HM, Hasanin E, Kahaleh M, Alnaser B, Ibrahim N
Arab J Gastroenterol
· 2025 Aug · PMID 40582901
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BACKGROUND: Celiac Disease (CeD) is a chronic immunological illness. So far, the only known treatment for CeD is a lifelong gluten-free diet. However, enzyme therapy was proposed as an alternative. This study aimed to as...BACKGROUND: Celiac Disease (CeD) is a chronic immunological illness. So far, the only known treatment for CeD is a lifelong gluten-free diet. However, enzyme therapy was proposed as an alternative. This study aimed to assess the impact of Latiglutenase, an example of enzyme therapy, on CeD patients compared to a placebo through a comprehensive assessment of existing literature. METHODS: We searched the following databases: Scopus, Web of Science, Cochrane Central Library, and PubMed from their respective inception date to February 18, 2024. We included randomized controlled trials comparing Latiglutenase with a placebo, with accessible full text in English. Outcomes included symptoms and histological findings improvement. We used the Revman 5.4 software to conduct the statistical analysis. For assessing the risk of bias, we utilized the Cochrane Collaboration tool ROB 2. RESULTS: Data from five randomized controlled trials was collected, with 1003 participants meeting the inclusion criteria. We found no significant differences between the Latiglutenase group and placebo group regarding adverse events like bloating (P = 0.55), nausea (P = 0.43), vomiting (P = 0.39), diarrhea (P = 0.83), tiredness (P = 0.83), headache (P = 0.08), and flatulence (P = 0.64); and histological findings like villous height to crypt depth ratio (Vh:Cd ratio), and intraepithelial lymphocytes (IELs) (mean difference (MD) = 0.19, 95 % confidence interval (CI) = [-0.24,0.62]; P = 0.39 and MD = -10.78, 95 % CI = [-26.97, 5.40]; P = 0.19, respectively). CONCLUSION: Latiglutenase did not significantly improve adverse events or histological findings in CeD patients. However, there is still a need for further RCTs to evaluate its effectiveness more precisely.