The Potential Role of Autophagy in Progression of Liver Fibrosis in Chronic Hepatitis B Patients Receiving Antiviral Treatment: A Brief Report.

Despite antiviral treatment, some patients with chronic hepatitis B (CHB) progress to cirrhosis. Enhancement of autophagy was implicated in the proliferation of hepatitis B in hepatocytes. This study aimed to evaluate the potential role of autophagy in the progression of liver fibrosis in patients receiving antiviral treatments and having completely inhibited viral replication. This descriptive-analytical study was designed and conducted in 2020 at Mottahhari Hepatitis Clinic affiliated with Shiraz University of Medical Science (Shiraz, Iran). Patients who were on anti-hepatitis B nucleotide treatments for at least two years, and those who were not cirrhotic at baseline but later progressed to cirrhosis were identified to be included in the case group. Besides, for the control group, patients on the nucleotide regimens who did not have cirrhosis at baseline or during follow-up were randomly selected. Ultimately, 16 cases and 14 controls were included in the study. Data were analyzed using SPSS software, and P<0.05 was considered statistically significant. Serum Beclin-1 and LC3 levels were compared between the two groups using enzyme-linked immunosorbent assays. The t test was used to assess the statistical differences between the case and control groups. Beclin-1 level was significantly higher in cirrhosis patients than the control group (1283±244 vs. 1063±257, P=0.024). However, there was no statistical difference between the level of LC3 in the cirrhotic group (168±31) and the control group (150±16) (P=0.065). Autophagy may have a role in the progression of cirrhosis in patients with CHB. Future larger prospective studies are required to determine the effect of blocking on the progression of liver disease in this population A preprint of this study was published at https://www.researchsquare.com/article/rs-1435490/v1.pdf.

The modulation of autophagy and unfolded protein response by ent-kaurenoid derivative CPUK02 in human colorectal cancer cells.

BACKGROUND: CPUK02 (15-Oxosteviol benzyl ester) is a semi-synthetic derivative of stevioside known for its anticancer effects. It has been reported that the natural compound of stevioside and its associated derivatives enhances the sensitivity of cancer cells to conventional anti-cancer agents by inducing endoplasmic reticulum (ER) stress. In response to ER stress, autophagy and unfolded protein responses (UPR) are activated to restore cellular homeostasis. Consequently, the primary aim of this study is to investigate the impact of CPUK02 treatment on UPR and autophagy markers in two colorectal cancer cell lines. METHODS: HCT116 and SW480 cell lines were treated with various concentrations of CPUK02 for 72 h. The expression levels of several proteins and enzymes were evaluated to investigate the influence of CPUK02 on autophagy and UPR pathways. These include glucose-regulated protein 78 (GRP78), Inositol-requiring enzyme 1-α (IRE1-α), spliced X-box binding protein 1 (XBP-1 s), protein kinase R-like ER kinase (PERK), C/EBP homologous protein (CHOP), Beclin-1, P62 and Microtubule-associated protein 1 light chain 3 alpha (LC3ßII). The evaluation was conducted using western blotting and quantitative real-time PCR techniques. RESULTS: The results obtained indicate that the treatment with CPUK02 reduced the expression of UPR markers, including GRP78 and IRE1-α at protein levels and XBP-1 s, PERK, and CHOP at mRNA levels in both HCT116 and SW480 cell lines. Furthermore, CPUK02 also influenced autophagy by decreasing Beclin-1 and increasing P62 and LC3ßII at mRNA levels in both HCT116 and SW480 treated cells. CONCLUSIONS: The study findings suggest CPUK02 may exert its cytotoxic effects by inhibiting UPR and autophagy flux in colorectal cancer cells.

Correction: Dastghaib et al. Simvastatin Induces Unfolded Protein Response and Enhances Temozolomide-Induced Cell Death in Glioblastoma Cells. Cells 2020, 9, 2339.

In the original publication [...].

Melittin as an Activator of the Autophagy and Unfolded Protein Response Pathways in Colorectal HCT116 Cell Line.

Background: The potential anticancer effect of melittin has motivated scientists to find its exact molecular mechanism of action. There are few data on the effect of melittin on the UPR and autophagy as two critical pathways involved in tumorigenesis of colorectal and drug resistance. This study aimed to investigate the effect of melittin on these pathways in the colorectal cancer (CRC) HCT116 cells. Methods: MTT method was carried out to assess the cytotoxicity of melittin on the HCT116 cell line for 24, 48, and 72 h. After selecting the optimal concentrations and treatment times, the gene expression of autophagy flux markers (LC3-ßII and P62) and UPR markers (CHOP and XBP-1s) were determined using qRT-PCR. The protein level of autophagy initiation marker (Beclin1) was also determined by Western blotting. Results: MTT assay showed a cytotoxic effect of melittin on the HCT116 cells. The increase in LC3-ßII and decrease in P62 mRNA expression levels, along with the elevation in the Beclin1 protein level, indicated the stimulatory role of melittin on the autophagy. Melittin also significantly enhanced the CHOP and XBP-1s expressions at mRNA level, suggesting the positive role of the melittin on the UPR activation. Conclusion: This study shows that UPR and autophagy can potentially be considered as two key signaling pathways in tumorigenesis, which can be targeted by the BV melittin in the HCT116 cells. Further in vivo evaluations are recommended to verify the obtained results.

Examining the expression of low-density lipoprotein receptor (LDLR) and low-density lipoprotein receptor-related protein 6 (LRP6) genes in breast cancer cell lines.

Cholesterol and the Wnt/ß-catenin pathway have an effective role in the proliferation, survival, drug resistance, immune exhaustion, and metastasis of all types of cancer cells. Considering the role of LDLR and LRP6 proteins in cholesterol uptake by cells and activation of Wnt/ß-catenin pathway, this study aims to examine the gene expression of LDLR and LRP6 in cell lines of breast cancer. Human breast cancer cell lines MCF7, MD468 and SKBR3 were cultured in suitable conditions and after extracting total RNA from them, real-Time PCR was used to measure the levels of gene expression for LDLR and LRP6. Our results showed that the expression of LDLR and LRP6 genes is significantly increased in MCF7 and MD468 cells compared to SKBR3 cells. These results suggest that LRP6 and LDLR can be considered as a therapeutic target in tumors that have a genetic profile similar to MCF7 and MD468 cells.

The effects of thymidylate synthase 3'UTR genotype on methylation of tumor-specific genes promoter in 22 colorectal cancer patients from southern Iran.

To investigate the effects of thymidylate synthase (TS) 3'UTR genotype on promotor methylation of tumor-related genes in 22 patients with sporadic colorectal cancer (CRC) from southern Iran. We evaluated the correlations of TS 3'UTR genotype with promoter methylation of hTERT, hMLH1, MSH2, MMP2, CDH1, p14, p16, and p21 genes in CRC patients. The polymorphism of TS 3'UTR was evaluated through mutagenically specific PCR. The genes promoter methylation was determined using methylation-specific PCR. For 10 patients, the gene expression profile of epigenetic regulating enzymes, histone deacetylases (HDACs) and DNA methyltransferases (DNMTs), was also examined in both tumor and normal adjacent tissues by quantitative real time PCR. There was a significant association between the hMLH1 methylation and age of patients (P= 0.039) and also between MSH2 methylation and tumor site (P= 0.036). There was insignificant association between gene-specific methylation and TS 3'UTR genotype. However, all polymorphic genotypes of TS were associated with higher methylation of hMLH1 and CDH1 and lower methylation of MSH2. The -6bp/+6bp (heterozygous mutant) and [-6bp/+6bp, +6bp/+6bp] (homozygous mutant) genotypes resulted in higher methylation of p16, and -6bp/+6bp and [-6bp/+6bp, +6bp/+6bp] genotypes were correlated with lower methylation of MMP2. The overexpression of epigenetic enzymes, HDACs and DNMTs, was also demonstrated. There was no association between DNMTs transcript levels and gene-specific hypermethylation. The polymorphic TS genotypes, especially -6bp/+6bp, could affect methylation frequencies of studied genes. Moreover, promoter methylation status was not dependent on DNMTs gene expression. Large sample size studies may contribute to validate these findings.

Biosynthesis of palladium, platinum, and their bimetallic nanoparticles using rosemary and ginseng herbal plants: evaluation of anticancer activity.

In this research, palladium (II) and platinum (II), as well as their bimetallic nanoparticles were synthesized using medicinal plants in an eco-friendly manner. Rosemary and Ginseng extracts were chosen due to their promising anticancer potential. The synthesized nanoparticles underwent characterization through FT-IR spectroscopy, DLS, XRD, EDX, SEM, and TEM techniques. Once the expected structures were confirmed, the performance of these nanoparticles, which exhibited an optimal size, was evaluated as potential anticancer agents through in vitro method on colon cancer cell lines (Ls180, SW480). MTT assay studies showed that the synthesized nanoparticles induced cell death. Moreover, real-time PCR was employed to investigate autophagy markers and the effect of nanoparticles on the apoptosis process, demonstrating a significant effect of the synthesized compounds in this regard.

Comparison of the teaching clinical biochemistry in face-to-face and the flex-flipped classroom to medical and dental students: a quasi-experimental study from IRAN.

INTRODUCTION: Biochemistry is one of the main courses of basic sciences in the medical curriculum, along with other difficult subjects that are difficult to learn. The emergence of new technologies has made it possible to test new methods such as e-Learning. In this study, we compared two methods of Flex-Flipped Classroom (FFC) and face-to-face. METHOD: A quasi-experimental research was done which involved both medical and dental students studying the clinical biochemistry course in the joint semester in 2019. A total of 100 medical students were trained in biochemistry through face-to-face teaching, and 60 dental students were trained in the same course through the FFC model. Three researcher-made tools were used to compare the two groups to assess the student's satisfaction, scores, and self-evaluation. The content validity of the tools was checked using the opinions of 10 experts through the CVI index. The results were analyzed using one-sample t-tests, independent t-tests, and ANOVA. RESULTS: Both groups scored significantly more than the cut-off-point (Mean > 3.5) in their average scores of the total and sub-components of the self-evaluation questionnaire (P < 0.05). Face-to-face teaching was viewed more favorably than the FFC teaching except for considering the flexibility (4.14 ± 1.55), but the difference was not significant (P > 0.05). The students' knowledge score in the FFC was slightly higher than that in the face-to-face method, but this difference was not significant(P = 0.758). CONCLUSION: Both face-to-face and FFC methods were effective according to the students, but the level of satisfaction with the face-to-face method was higher. It seems that teacher-student interaction is an important factor in students' preferences. However, the students preferred the flexibility of multimedia. It seems necessary to use the advantages of each method in a model appropriate to the students' conditions and available facilities.

Circulating Nucleic Acids in Colorectal Cancer: Diagnostic and Prognostic Value.

Colorectal cancer (CRC) is the third most prevalent cancer in the world and the fourth leading cause of cancer-related mortality. DNA (cfDNA/ctDNA) and RNA (cfRNA/ctRNA) in the blood are promising noninvasive biomarkers for molecular profiling, screening, diagnosis, treatment management, and prognosis of CRC. Technological advancements that enable precise detection of both genetic and epigenetic abnormalities, even in minute quantities in circulation, can overcome some of these challenges. This review focuses on testing for circulating nucleic acids in the circulation as a noninvasive method for CRC detection, monitoring, detection of minimal residual disease, and patient management. In addition, the benefits and drawbacks of various diagnostic techniques and associated bioinformatics tools have been detailed.

Molecular Modelling of Resveratrol Derivatives with SIRT1 for the Stimulation of Deacetylase Activity.

BACKGROUND: Resveratrol is a polyphenol that is found in plants and has been proposed to have a potential therapeutic effect through the activation of SIRT1, which is a crucial member of the mammalian NAD+-dependent deacetylases. However, how its activity is enhanced toward specific substrates by resveratrol derivatives has not been studied. This study aimed to evaluate the types of interaction of resveratrol and its derivatives with SIRT1 as the target protein, as well as to find out the best ligand with the strangest interaction with SIRT1. METHODS: In this study, we employed the extensive molecular docking analysis using AutoDock Vina to comparatively evaluate the interactions of resveratrol derivatives (22 molecules from the ZINC database) as ligands with SIRT1 (PDB ID: 5BTR) as a receptor. The ChemDraw and Chem3D tools were used to prepare 3D structures of all ligands and energetically minimize them by the MM2 force field. RESULTS: The molecular docking and visualizations showed that conformational change in resveratrol derivatives significantly influenced the parameter for docking results. Several types of interactions, including conventional hydrogen bonds, carbon-hydrogen bonds, Pi-donor hydrogen bonds, and Pi-Alkyl, were found via docking analysis of resveratrol derivatives and SIRT1 receptors. The possible activation effect of resveratrol 4'-(6-Galloylglucoside) with ZINC ID: ZINC230079516 with higher binding energy score (-46.8608 kJ/mol) to the catalytic domain (CD) of SIRT1 was achieved at the maximum value for SIRT1, as compared to resveratrol and its other derivatives. CONCLUSION: Finally, resveratrol 4'-(6-Galloylglucoside), as a derivative for resveratrol, has stably interacted with the CD of SIRT1 and might be a potential effective activator for SIRT1.

BAMLET (Bovine α-lactalbumin made lethal to tumor cells) inhibits autophagy flux and induces apoptosis via down-regulation of protein kinase CK1α and attenuation of the AKT/p-ß-catenin (S552) pathway in RAS-mutated human colorectal HCT 116 cells.

Objectives: Oncogenic RAS mutations occur in nearly 50% of colorectal cancer cases and are usually dependent on the autophagy mechanism to maintain tumorigenesis. We have recently demonstrated that CK1α controls autophagy machinery possibly through the AKT/p-ß-catenin (S552) signaling in colorectal cancer cells harboring RAS mutation. It has been found that a lipid-protein complex comprising oleic acid binds to human α-lactalbumin, known as HAMLET (human α -lactalbumin made lethal to tumor cells), targets a broad range of kinases including CK1α. Therefore, this study was designed to investigate the effects of BAMLET (bovine α -lactalbumin made lethal to tumor cells, the bovine counterpart of HAMLET) on CK1α expression, AKT/Phospho-ß-catenin (S552) pathway, and autophagy flux in RAS-mutated human colorectal HCT 116 cells. Materials and Methods: For this purpose, HCT116 cells were treated with BAMLET and casein kinase 1 inhibitor (D4476), and quantitative real-time polymerase chain reaction (RT-qPCR) and western blot analysis were used to measure the proteins and genes of the AKT/Phospho-ß-catenin (S552) pathway and autophagy. Apoptosis was measured by flow-cytometry. Results: We found that BAMLET significantly reduced cell viability and decreased the expression of CK1α. Additionally, BAMLET inhibited autophagy flux and enhanced the ability of CK1α inhibitor D4476 to impair autophagy flux, which was accompanied by an increase in the apoptosis percentage. We also observed that BAMLET empowered D4476 to down-regulate the AKT/Phospho-ß-catenin (S552) axis. Conclusion: BAMLET hampers autophagy flux and leads to apoptosis induction, possibly, by reducing the expression of CK1α and attenuation of the AKT/Phospho-ß-catenin (S552) axis.

Stemness targeting of colorectal cell lines mediated by BAMLET and 5-Flourouracil.

PURPOSE: Stemness is the potential for self-renewal and repopulation causing the relapse, progression, and drug resistance of colorectal cancer. We investigated the effects of bovine alpha-lactalbumin made lethal to tumor cells and 5-Flourouracil consisting of bovine α-lactalbumin protein and oleic acid, on colorectal cancer cells on stemness. METHODS: The quantitative real-time polymerase chain reaction assessed the expression levels of stemness-related genes (c-myc, Lgr5, OCT4). Expression of stemness-related surface markers (CD44 and CD24) was also measured by the flow cytometry technique following the treatments. RESULTS: Our results indicated decreased expression levels of C-Myc, Lgr5, oct4 as the stemness-related genes (P < 0.0001), and reduced population of CD44+ as the stemness-related cell surface marker upon treatment with BAMLET and 5-Flourouracil. BAMLET inhibited the stemness more effectively than 5-Flourouracil (P < 0.0001). CONCLUSION: Based on the result, inhibition of the Stemness related-genes (C-Myc, Lgr5, Oct4) and the surface markers (CD 24+ and CD44+) is a promising therapeutic approach using BAMLET.

The Effects of Statins on Respiratory Symptoms and Pulmonary Fibrosis in COVID-19 Patients with Diabetes Mellitus: A Longitudinal Multicenter Study.

The aim of this prospective cohort study was to explore the effect of statins on long-term respiratory symptoms and pulmonary fibrosis in coronavirus disease 2019 (COVID-19) patients with diabetes mellitus (DM). Patients were recruited from three tertiary hospitals, categorized into Statin or Non-statin groups, and assessed on days 0, 28, and 90 after symptoms onset to record the duration of symptoms. Pulmonary fibrosis was scored at baseline and follow-up time points by high-resolution computed tomography scans. Each group comprised 176 patients after propensity score matching. Data analysis revealed that the odds of having cough and dyspnea were significantly higher in the Non-statin group compared to the Statin group during the follow-up period. Overall, there was no significant difference in the change in pulmonary fibrosis score between groups. However, Non-statin patients with > 5 years of DM were more likely to exhibit a significantly higher fibrosis score during the follow-up period as compared to their peers in the Statin group. Our results suggest that the use of statins is associated with a lower risk of developing chronic cough and dyspnea in diabetic patients with COVID-19, and may reduce pulmonary fibrosis associated with COVID-19 in patients with long-term (> 5 years) DM.

Resveratrol promotes liver cell survival in mice liver-induced ischemia-reperfusion through unfolded protein response: a possible approach in liver transplantation.

BACKGROUND: Ischemia-reperfusion (I/R) of the liver is a multifactorial condition that happens during transplantation and surgery. The deleterious effects of I/R result from the acute production of reactive oxygen species (ROS), which can trigger immediate tissue damage and induce a series of destructive cellular responses, including apoptosis organ failure and inflammation. The production of ROS in the I/R process can damage the antioxidant system and cause liver damage. Resveratrol has been shown to have antioxidant properties in several investigations. Here, we address the therapeutic effect of resveratrol on I/R-induced liver injury by focusing on unfolded protein response (UPR) signaling pathway. METHODS: Five minutes before reperfusion, resveratrol was injected into the tail vein of mice. They were ischemic for 1 h and then re-perfused for 3 h before being slaughtered (I/R). The activity of liver enzymes and the expression levels of genes involved in the unfolded protein response pathway were used to measure the hepatic damage. RESULTS: Our results revealed that the low dose of resveratrol (0.02 and 0.2 mg/kg) post-ischemic treatment significantly reduced the ALT and AST levels. In addition, compared with the control group, the expression of UPR pathway genes GRP78, PERK, IRE1α, CHOP, and XBP1 was significantly reduced in the resveratrol group. In the mice that received lower doses of resveratrol (0.02 and 0.2 mg/kg), the histopathological changes induced by I/R were significantly improved; however, the highest dose (2 mg/kg) of resveratrol could not significantly protect and solve the I/R damage. CONCLUSION: The findings of this study suggest that hepatic ischemia occurs after liver transplantation and that receiving low-dose resveratrol treatment before reperfusion may promote graft survival through inhibition of UPR arms, especially PERK and IRE1α.

Epigenetic regulation of autophagy in gastrointestinal cancers.

The development of novel therapeutic approaches is necessary to manage gastrointestinal cancers (GICs). Considering the effective molecular mechanisms involved in tumor growth, the therapeutic response is pivotal in this process. Autophagy is a highly conserved catabolic process that acts as a double-edged sword in tumorigenesis and tumor inhibition in a context-dependent manner. Depending on the stage of malignancy and cellular origin of the tumor, autophagy might result in cancer cell survival or death during the GICs' progression. Moreover, autophagy can prevent the progression of GIC in the early stages but leads to chemoresistance in advanced stages. Therefore, targeting specific arms of autophagy could be a promising strategy in the prevention of chemoresistance and treatment of GIC. It has been revealed that autophagy is a cytoplasmic event that is subject to transcriptional and epigenetic regulation inside the nucleus. The effect of epigenetic regulation (including DNA methylation, histone modification, and expression of non-coding RNAs (ncRNAs) in cellular fate is still not completely understood. Recent findings have indicated that epigenetic alterations can modify several genes and modulators, eventually leading to inhibition or promotion of autophagy in different cancer stages, and mediating chemoresistance or chemosensitivity. The current review focuses on the links between autophagy and epigenetics in GICs and discusses: 1) How autophagy and epigenetics are linked in GICs, by considering different epigenetic mechanisms; 2) how epigenetics may be involved in the alteration of cancer-related phenotypes, including cell proliferation, invasion, and migration; and 3) how epidrugs modulate autophagy in GICs to overcome chemoresistance.

Evidence of histone modification affecting ARID1A expression in colorectal cancer cell lines.

Aim: The current study aimed to focus on the role of histone deacetylation in reduced ARID1A expression in colorectal cancer cell lines. Background: ARID1A, a subunit of the switch/sucrose nonfermentable chromatin remodeling complex, has emerged as a bona fide tumor suppressor and is frequently downregulated and inactivated in multiple human cancers. Epigenetic modifications play an important role in dysregulation of gene expression in cancer. DNA methylation has been reported as an important regulator of ARID1A expression in colorectal cancer cell lines; however, the histone modification role in ARID1A suppression in colorectal cancer remains unclear. Methods: The expression levels of ARID1A mRNA were determined using real-time quantitative PCR in colorectal cancer cell lines including HCT116, SW48, HT29, SW742, LS180, and SW480. To evaluate the effect of histone deacetylation on ARID1A expression, all cell lines were treated with trichostatin A (TSA), a histone deacetylase inhibitor. SPSS software (Version 23) and GraphPad Prism (Version 6.01) were applied for data analysis using one-way ANOVA, followed by Tukey's multiple comparison tests. Results: Treatment of colorectal cancer cell lines with TSA increased ARID1A expression in a cell line-dependent manner, suggesting that histone deacetylation is at least one factor contributing to ARID1A downregulation in colorectal cancer. Conclusion: Histone deacetylase inhibitors might provide a strategy to restore ARID1A expression and may bring benefits to the colorectal cancer patients with a broader range of genetic backgrounds.

Epigenetic regulation of autophagy in coronavirus disease 2019 (COVID-19).

The coronavirus disease 2019 (COVID-19) pandemic has become the most serious global public health issue in the past two years, requiring effective therapeutic strategies. This viral infection is a contagious disease caused by new coronaviruses (nCoVs), also called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Autophagy, as a highly conserved catabolic recycling process, plays a significant role in the growth and replication of coronaviruses (CoVs). Therefore, there is great interest in understanding the mechanisms that underlie autophagy modulation. The modulation of autophagy is a very complex and multifactorial process, which includes different epigenetic alterations, such as histone modifications and DNA methylation. These mechanisms are also known to be involved in SARS-CoV-2 replication. Thus, molecular understanding of the epigenetic pathways linked with autophagy and COVID-19, could provide novel therapeutic targets for COVID-19 eradication. In this context, the current review highlights the role of epigenetic regulation of autophagy in controlling COVID-19, focusing on the potential therapeutic implications.

Aqueous extract of Stevia rebaudiana (Bertoni) Bertoni abrogates death-related signaling pathways via boosting the expression profile of oxidative defense systems.

Indigenous inhabitants of South America and other areas have been using stevia as a traditional medicine for years, but its impact on cell signaling pathways has not been well studied yet. We evaluated the impacts of aqueous extract of Stevia rebaudiana (Bertoni) Bertoni on the expression of the selected genes involved in significant cell death modalities, including p53-DNA damage and the cellular antioxidative defense in pancreatic tissues in STZ-induced diabetic rats and murine pancreatic cell lines. The in vivo study revealed that aqueous extract of Stevia significantly upregulated the expression of GSTM1 and P1 and GPX (4.67, 12.08, and 2.81 fold, respectively; all p < .05) along with significant downregulation of the genes which were upregulated by STZ, including apoptotic genes caspase-3 and -9 (-9.80 and -4.16 fold, p < .05, respectively) and necroptotic genes, RIP1K, 2 K, and 3 K (-9.48, -2.70, and -12.9 fold, respectively, all p < .05). In vitro studies also revealed comparable results. In conclusion, the observed clinical improvements in diabetic rats are the result of overexpression of major genes of antioxidative defense systems in the course of a significant downregulation of major cell death modalities. PRACTICAL APPLICATIONS: The popularity of noncaloric sweeteners, including stevia, has rocketed in recent years, but the consumption of stevia as traditional medicine has a long history. The findings of the current study provide strong mechanistic lines of evidence supporting the beneficial biological effects of stevia as a noncaloric sweetener in diabetes.

Cotransplant With Pancreatic Islet Homogenate Improved Survival and Long-Term Efficacy of Islet Transplant in Streptozotocin-Diabetic Rats.

OBJECTIVES: Pancreatic islet transplant is suggested as a promising treatment option in diabetes, but the number of viable and functional islets and the long-term efficacy of transplanted islets have not been satisfactory. Islet isolation leads to destruction of the extracellular matrix and loss of trophic support of islets, which reduces their survival and function. Reconstruction of islet microenvironment with biomaterials may preserve islet survival and graft efficacy. Accordingly, we investigated the effects of pancreatic islet homogenate on islet quality and graft outcomes in diabetic rats. MATERIALS AND METHODS: Islets were isolated from the pancreas of Sprague Dawley rats and were cultured with or without pancreatic islet homogenate. Before transplant, viability, insulin content, and insulin released from cultured islets were assessed. Islets were then transplanted into subcapsular space of diabetic rat kidney. Transplant outcomes were evaluated by plasma glucose and insulin levels, glucose tolerance tests, and stress oxidative markers. RESULTS: Viability and insulin release in the pancreatic islet homogenate-treated islets were significantly higher than that in the control islets. After transplant of islets, recipient rats with pancreatic islet homogenate showed significant decreases in blood glucose and malondialdehyde levels and increases in superoxide dismutase activity and plasma insulin levels. CONCLUSIONS: Islet treatment with pancreatic islet homogenate could improve islet survival and transplant function and outcomes. Oxidative stress reduction might be a secondary beneficial effect of improved quality of treated islets.