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Pulmonary fibrosis leads to increased mortality but is poorly understood. Fibrotic progression is associated with abnormal wound repair and an increase in myofibroblast cell populations. Here we investigate how the myofibroblast population is impacted by unique compression-induced apoptosis derived from mechanical strain characteristic of asthma. Using a mechanical device, both static and dynamic mechanical strains were applied to alginate/gelatin/CaCl 2 scaffolds containing fibroblasts and myofibroblasts. As cell groups were stimulated with 30 % static strain for 12 h, fibroblast and myofibroblast cell groups showed increased cell apoptosis by 5.55 % and 19.56 %, respectively, compared to control groups. Additionally, myofibroblasts exhibited higher susceptibility to apoptosis induction than did fibroblasts. Comparing dynamic and static loading modes, dynamic loading resulted in a higher apoptosis rate of fibroblast and myofibroblast cells, indicating its potential to induce apoptosis effectively. These findings suggest that mechanical stimulation can be considered a promising approach to induce apoptosis in myofibroblasts, thus offering the potential for future approaches to treating pulmonary fibrosis. Moreover, mechanical loads can be designed for other diseases, selectively reducing or increasing apoptosis in either hard or soft cell groups, based on specific application needs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Exosomes (Exos), natural nanovesicles released by various cell types, show potential as an effective drug delivery platform due to their intrinsic role as transporters of biomolecules between different cells. However, Exos functionalization with targeting ligands is a critical step to enhance their targeting capability, which could be challenging. In this study, Exos were modified to specifically bind to CD44-positive cells by anchoring chondroitin sulfate (CS) to their surface. Exo modification was facilitated with CS conjugation with alpha-tocopherol succinate (TOS) as an anchorage. The modified Exos were utilized for delivering curcumin (Cur) to pancreatic cancer (PC) cells. In vitro Cur release studies revealed that Exos play a crucial role in maintaining Cur within themselves, demonstrating their potential as effective carriers for drug delivery to targeted locations. Notably, Cur loaded into the modified Exos exhibited enhanced cytotoxicity compared to unmodified Exo-Cur. Meanwhile, Exo-Cur-TOS-CS induced apoptosis more effectively in AsPC-1 cells than unmodified Exos (70.2 % versus 56.9 %). It is worth mentioning that with CD44-mediated cancer-specific targeting, Exo-CS enabled increased intracellular accumulation in AsPC-1 cells, showing promise as a targeted platform for cancer therapy. These results confirm that Exo modification has a positive impact on enhancing the therapeutic efficacy and cytotoxicity of drugs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Liver fibrosis is characterized by the excessive deposition and accumulation of extracellular matrix components, mainly collagens, and occurs in response to a broad spectrum of triggers with different etiologies. Under stress conditions, autophagy serves as a highly conserved homeostatic system for cell survival and is importantly involved in various biological processes. Transforming growth factor-β1 (TGF-β1) has emerged as a central cytokine in hepatic stellate cell (HSC) activation and is the main mediator of liver fibrosis. A growing body of evidence from preclinical and clinical studies suggests that TGF-β1 regulates autophagy, a process that affects various essential (patho)physiological aspects related to liver fibrosis. This review comprehensively highlights recent advances in our understanding of cellular and molecular mechanisms of autophagy, its regulation by TGF-β, and the implication of autophagy in the pathogenesis of progressive liver disorders. Moreover, we evaluated crosstalk between autophagy and TGF-β1 signalling and discussed whether simultaneous inhibition of these pathways could represent a novel approach to improve the efficacy of anti-fibrotic therapy in the treatment of liver fibrosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Aims: As conventional therapeutics failed to provide satisfied outcomes against one of the most prevalent cancers, colorectal cancer (CRC), we purposed to implicate MicroRNA (miR)-34a, as a major tumor suppressor, to be delivered by tumor-derived exosomes (TEXs) and investigated its anti-tumor functions in-vivo., Main Methods: TEXs were isolated from CT-26 cell line and loaded with miR-34a mimic. Then, mice bearing CRC were treated with miR-34a-enriched TEX (TEX-miR-34a) and then examined for the relative tumor-suppressive impacts of the TEX as well as its potential in promoting an anti-tumor immune response., Key Findings: TEX-miR-34a significantly reduced tumor size and prolonged survival of mice bearing CRC. TEX-miR-34a was able to diminish gene expressions related to invasion, angiogenesis and immune evasion. It was also capable of inducing T cell polarization toward CD8+ T subsets among tumor-infiltrating lymphocytes, draining lymph nodes (DLNs) and spleen cells. Moreover, cytotoxic T cells were professionally induced in mice receiving TEX-miR-34a and the secretion of interleukin (IL)-6, IL-17A and tumor necrosis factor (TGF)-β was reduced in DLNs. However, the enhanced levels of interferon-γ were evaluated in DLN and spleen displaying the polarization of anti-tumor immune responses. Interestingly, mice receiving TEX alone showed a noticeable reduction in certain oncogenic gene expressions as well as IL-17A secretion in DLNs., Significance: TEX-miR-34a demonstrated the potential to induce beneficial anti-tumor immune responses and TEXs, aside from the delivery function of miRNA, revealed certain anti-tumor beneficial characteristics which could introduce TEX-miR-34a as a promising approach in CRC combination therapies., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Aims: EMT is the process by which a polarized epithelial cell undergoes several changes leading to highly invasive and fibroblast-like morphology. It has been described that miR-375 is inversely associated with EMT in cancerous patients and can effectively inhibit invasion and migration of tumor cells. Here, we investigate whether miR-375 mimic delivered by tumor-derived exosomes could reverse EMT process., Main Methods: The exosomes were isolated from HT-29 and SW480. Subsequently, exosomes were loaded with miR-375-3p mimic applying modified calcium chloride method. Quantitative real-time PCR was used for evaluation of the loading efficiency of miR-375 mimic in the exosomes. The effects of miR-375 loaded tumor exosomes (TEXomiR) on EMT process investigated using flow cytometry, cell morphology, and invasion and migration assay., Key Findings: The in vitro results showed that the tumor derived exosomes can efficiently deliver miR-375 mimic to reduce the expression of β-catenin, vimentin, ZEB1, and snail. In contrast, TEXomiR significantly increased the expression of E- cadherin in EMT process. Furthermore, the migration and invasion abilities of HT-29 and SW480 cells were inhibited by TEXomiR. The expression of CD44 and CD133 are increased in EMT process. Flow cytometry evaluation demonstrated that treatment with TEXomiR significantly decreased the expression of CD44 and CD133 in SW480 cell line., Significance: Our results imply that colon cancer cells-derived exosomes could be used as an effective nonvehicle to deliver miR-375-3p mimic. Moreover, TEXomiR may be a potent therapeutic agent for the treatment of metastatic colorectal cancer., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Aims: The clinical efficiency of dendritic cell (DC) therapy needs to be improved. Exosomes, as membrane nano-vesicles, carry bio-macromolecules and play essential roles in intercellular crosstalk. Here, it is proposed that tumor cell-derived exosomes could function as vehicles to deliver exogenous miRNA-155 into DCs, for simultaneous miRNA delivery and antigen priming of DCs. Following optimization of the miRNA-155 delivery, the effect of exogenous miRNA-155 overexpression on DCs is evaluated., Main Methods: For this purpose, exogenous miRNA-155 was electroporated with various voltages (0.100, 0.200, and 0.300 kV) into tumor cell-derived exosomes with various concentrations, and then DCs were treated with miRNA-155 loaded exosomes. To assess the effect of miRNA-155 loaded exosomes on DCs, the expression levels of IL12p70, IFN-γ, and IL10 in culture supernatants were measured by ELISA. Then, the expression profiles of DC surface markers, including CD11C, MHCII (I/A-I/E), CD86, CD40, and CD83 were investigated by flow cytometry., Key Findings: Concerning the results, exogenous miRNA-155 can be successfully inserted into tumor cell derived exosomes. Loading conditions for tumor cell-derived exosomes were enhanced for utilization as vehicles to deliver miRNA-155 into DCs. Analysis of the surface molecule revealed that miRNA-155 can increase the expression levels of MHCII (I/A-I/E), CD86, CD40, and CD83. ELISA analysis indicates that miRNA-155 can significantly increase, the levels of IL12p70, IFN-γ, and IL10., Significance: Finally, it can be stated that miRNA-155 could be a candidate for dendritic cell maturation. This method can be applied in the modification of target cells in in vitro studies., (Copyright © 2019. Published by Elsevier Inc.)

Background: The cag pathogenicity island (PAI), which can be divided into two parts, cagI and cagII, is the most well-known virulence factor of Helicobacter pylori., Aims: We investigated the association between genetic variations within the cag PAI (cagA and cagE in the cagI and cagT in the cagII) and clinical outcomes in Iranian patients., Subjects: A total of 231 patients including 182 patients with gastritis, 41 with peptic ulcer and 8 with gastric cancer., Methods: The presence of the cagA, cagE and cagT genes were measured by polymerase chain reaction and the results were compared with clinical outcomes and gastric histology., Results: The cagA, cagE and cagT genes were found in 154 (66.7%), 90 (39.0%) and 70 (30.3%) of clinical isolates. At least 144 (62.3%) strains possessed partially deleted cag PAI (e.g., 69 [29.9%] strains were cagA-positive, but cagE and cagT-negative)., Conclusion: The single genes as well as the combination of genes in the cag PAI appeared not to be useful markers to predict H. pylori-related diseases in Iranian patients. The genomic sequences of the cag PAI in Iranian strains might be considerably different from those in other geographic locations.