Long noncoding RNAs (lncRNAs) are involved in the pathology of colorectal cancer (CRC). Current efforts to eradicate CRC predominantly focused on targeting the proliferation of rapidly growing cancer epithelial cells. This is largely ineffective with resistance arising in most tumors after exposure to chemotherapy. Despite the long‐standing recognition of the crosstalk between carcinoma‐associated fibroblasts (CAFs) and cancer cells in the tumor microenvironment, how CAFs may contribute to drug resistance in neighboring cancer cells is not well characterized. Here, we show that lncRNA CCAL (colorectal cancer‐associated lncRNA) promotes oxaliplatin (Oxa) resistance of CRC cells. RNA‐ISH shows higher CCAL expressed in the tumor stroma compared to cancer nests of CRC tissues. Functional studies reveal that CCAL is transferred from CAFs to the cancer cells via exosomes, where it suppresses CRC cell apoptosis, confers chemoresistance and activates β‐catenin pathway in vitro and in vivo. Mechanistically, CCAL interacts directly with mRNA stabilizing protein HuR (human antigen R) to increase β‐catenin mRNA and protein levels. Our findings indicate that CCAL expressed by CAFs of the colorectal tumor stroma contributes to tumor chemoresistance and CCAL may serve as a potential therapeutic target for Oxa resistance.

Objective: The 2019 coronavirus disease (COVID-19) epidemic has raised international concern. Mental health is becoming an issue that cannot be ignored in our fight against it. This study aimed to explore the prevalence and factors linked to anxiety and depression in hospitalized patients with COVID-19. Methods: A total of 144 patients diagnosed with COVID-19 were included in this study. We assessed depression and anxiety symptoms using the Hospital Anxiety and Depression Scale (HADS), and social support using the Perceived Social Support Scale (PSSS) among patients at admission. Multivariate linear regression analyses were performed to identify factors associated with symptoms of anxiety and depression. Results: Of the 144 participants, 34.72% and 28.47% patients with COVID-19 had symptoms of anxiety or depression, respectively. The bivariate correlations showed that less social support was correlated with more anxious (r=-0.196, p<0.05) and depressive (r=-0.360,p<0.05) symptoms among patients with COVID-19. The multiple linear regression analysis showed that gender (β=1.446, p=0.034), age (β=0.074, p=0.003), oxygen saturation (β =-2.140, p=0.049), and social support (β =-1.545, p=0.017) were associated with anxiety for COVID-19 patients. Moreover, age (β=0.084, p=0.001), family infection with SARS-CoV-2 (β =1.515, p=0.027) and social support (β =-2.236, p<0.001) were the factors associated with depression. Conclusion: Hospitalized patients with COVID-19 presented features of anxiety and depression. Mental concern and appropriate intervention are essential parts of clinical care for those who are at risk.

Outer membrane vesicles (OMVs) are nanoscale lipid bilayer structures released by gram-negative bacteria. They share membrane composition and properties with their originating cells, making them adept at traversing cellular barriers. These OMVs have demonstrated exceptional membrane stability, immunogenicity, safety, penetration, and tumor-targeting properties, which have been leveraged in developing vaccines and drug delivery systems. Recent research efforts have focused on engineering OMVs to increase production yield, reduce cytotoxicity, and improve the safety and efficacy of treatment. Notably, gastrointestinal (GI) tumors have proven resistant to several traditional oncological treatment strategies, including chemotherapy, radiotherapy, and targeted therapy. Although immune checkpoint inhibitors have demonstrated efficacy in some patients, their usage as monotherapy remains limited by tumor heterogeneity and individual variability. The immunogenic and modifiable nature of OMVs makes them an ideal design platform for the individualized treatment of GI tumors. OMV-based therapy enables combination therapy and optimization of anti-tumor effects. This review comprehensively summarizes recent advances in OMV engineering for GI tumor therapy and discusses the challenges in the clinical translation of emerging OMV-based anti-tumor therapies.

In pancreatic ductal adenocarcinomas (PDAC), profound hypoxia plays key roles in regulating cancer cell behavior, including proliferation, migration, and resistance to therapies. The initial part of this research highlights the important role played by long noncoding RNA (lncRNA) MKLN1-AS, which is controlled by hypoxia-inducible factor-1 alpha (HIF-1α), in the progression of PDAC. Human samples of PDAC showed a notable increase in MKLN1-AS expression, which was linked to a worse outcome. Forced expression of MKLN1-AS greatly reduced the inhibitory impact on the growth and spread of PDAC cells caused by HIF-1α depletion. Experiments on mechanisms showed that HIF-1α influences the expression of MKLN1-AS by directly attaching to a hypoxia response element in the promoter region of MKLN1-AS.MKLN1-AS acts as a competitive endogenous RNA (ceRNA) by binding to miR-185-5p, resulting in the regulation of TEAD1 expression and promoting cell proliferation, migration, and tumor growth. TEAD1 subsequently enhances the development of PDAC. Our study results suggest that MKLN1-AS could serve as a promising target for treatment and a valuable indicator for predicting outcomes in PDAC. PDAC is associated with low oxygen levels, and the long non-coding RNA MKLN1-AS interacts with TEAD1 in this context. Graphical abstract

Chronic pancreatitis (CP) is marked by progressive fibrosis and the activation of pancreatic stellate cells (PSC), accompanied by the destruction of pancreatic parenchyma, leading to the loss of acinar cells (ACs). Few researches explored the mechanism by which damaged ACs (DACs) contribute to PSC activation and pancreatic fibrosis. Currently, there are no effective drugs for curing CP or limiting the progression of pancreatic fibrosis. In this research, co-culture with intact acinar cells (IACs) suppressed PSC activation, while co-culture with DACs did the opposite. Krüppel-like factor 4 (KLF4) was significantly upregulated in DACs and was established as the key molecule that switches ACs from PSC-suppressor to PSC-activator. We revealed the exosomes of IACs contributed to the anti-activated function of IACs-CS on PSC. MiRNome profiling showed that let-7 family is significantly enriched in IACs-derived exosomes (>30% miRNome), which partially mediates IACs' suppressive impacts on PSC. Furthermore, it has been observed that the enrichment of let-7 in exosomes was influenced by the expression level of KLF4. Mechanistic studies demonstrated that KLF4 in ACs upregulated Lin28A, thereby decreasing let-7s levels in ACs-derived exosomes, and thus promoting PSC activation. We utilized an adeno-associated virus specifically targeting KLF4 in ACs (shKLF4-pAAV) to suppress PSC activation in CP, resulting in reduced pancreatic fibrosis. IACs-derived exosomes hold potential as potent weapons against PSC activation via let-7s, while activated KLF4/Lin28A signaling in DACs diminished such functions. ShKLF4-pAAV holds promise as a novel therapeutic approach for CP.

Extracellular vesicles are fundamentally significant in the communication between cells. Outer Membrane Vesicles(OMVs) are a special kind of EVs produced by Gram-negative bacteria, which are minute exosome-like particles budding from the outer membrane, which have been found to play essential roles in diverse bacterial life events, including regulation of microbial interactions, pathogenesis promotion, stress responses and biofilm formation. Recently, and more researches have explored the substantial potentials of EVs as natural functional nanoparticles in the bioengineering applications in infectious diseases, cardiovascular diseases, autoimmune diseases and neurological diseases, such as antibacterial therapy, cancer drugs and immunoadjuvants, with several candidates in clinical trials showing promising efficacy. However, due to the poor understanding of sources, membrane structures and biogenesis mechanisms of EVs, progress in clinical applications still remains timid. In this review, we summarize the latest findings of EVs, especially in gastrointestinal tract tumours, to provide a comprehensive introduction of EVs in tumorigenesis and therapeutics.