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Insensitivity and resistance to 5-fluorouracil (5FU) remain as major hurdles for effective and durable 5FU-based chemotherapy in colorectal cancer (CRC) patients. In this study, we identified prostaglandin E synthase (PTGES)/prostaglandin E2 (PGE2) axis as an important regulator for 5FU sensitivity in CRC cells. We found that PTGES expression and PGE2 production are elevated in CRC cells in comparison to normal colorectal epithelial cells. Depletion of PTGES significantly enhanced the inhibitory effect of 5FU on CRC cell viability that was fully reverted by exogenous supplement of PGE2. Inhibition of PTGES enzymatic function, by either inducing loss-of-function mutant or treatment with selective inhibitors, phenocopied the PTGES depletion in terms of 5FU sensitization. Mechanistically, PTGES/PGE2 axis modulates glycolysis in CRC cells, thereby regulating the 5FU sensitivity. Importantly, high PTGES expression is correlated with poor prognosis in 5FU-treated CRC patients. Thus, our study defines PTGES/PGE2 axis as a novel therapeutic target for enhancing the efficacy of 5FU-based chemotherapy in CRC. Key words: colorectal cancer, prostaglandin E synthase, prostaglandin E2, 5-fluorouracil, chemotherapy, Introduction Colorectal cancer (CRC) remains one of the leading causes of cancer-related mortality worldwide (Dekker et al. 2019; Siegel et al. 2022). As a routine clinical therapeutic strategy for CRC [...]

Background: Chemoresistance remains a significant challenge in colorectal cancer (CRC) treatment, necessitating a deeper understanding of its underlying mechanisms. HOXC11 has emerged as a potential regulator in various cancers, but its role in CRC chemoresistance remains unclear. Methods: Sulforhodamine B assay was employed to assess the cell viability of CRC cells following treatment with chemotherapeutic drugs. Immunofluorescence staining was performed to examine the subcellular localization of HOXC11 in normal and chemoresistant CRC cells. The Seahorse mito stress test was conducted to evaluate the mitochondrial respiratory function of CRC cells. Real-time PCR was utilized to measure the expression level and copy number of mitochondrial DNA (mtDNA). Results: Our findings revealed that HOXC11 was overexpressed in CRC cells compared to normal colorectal cells and correlated with poorer prognosis in CRC patients. Knockout of HOXC11 reversed acquired chemoresistance in CRC cells. Furthermore, we observed a functional subset of HOXC11 localized to the mitochondria in chemoresistant CRC cells, which regulated mitochondrial function by modulating mtDNA transcription, thereby affecting chemoresistance. Conclusions: In summary, our study reveals that HOXC11 regulates mitochondrial function through the modulation of mtDNA transcription, impacting chemoresistance in colorectal cancer cells. These findings underscore the significance of understanding the molecular mechanisms underlying chemoresistance and highlight the potential therapeutic implications of targeting mitochondrial function in CRC treatment. [ABSTRACT FROM AUTHOR]

Internal hernia through an iatrogenic defect in the hepatic falciform ligament and acquired jejunal atresia in a 8-day-old neonate was reported. The PubMed, MEDLINE, CNKI, Wanfang and Weipu databases were searched The literature about the hepatic falciform ligament iatrogenic defect causing internal hernia was analysed. Ten other cases were collected from the world literature. Herniated intestinal necrosis was found in four cases. All cases were recovered uneventfully after operation. Internal herniation through an iatrogenic defect in the hepatic falciform ligament is extremely rare. However, the case reports are increasing, especially in the era of laparoscopic surgery. Adequate closure or open the defect is essential to prevent internal hernia occurrence. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is a common malignant tumor in gastrointestinal tract around the world. Emerging evidence has confirmed that long non-coding RNAs (lncRNAs) are closely connected to cell progression in cancers, including CRC. RT-qPCR assays were applied to detect the expression of LINC00882, miR-3619-5p and CTNNB1. Western blot assays were performed to measure the protein level of E-cadherin, N-cadherin and CTNNB1. Transwell assay was conducted to test the cell migration. Immunofluorescence (IF) assay was performed to measure the connected protein of EMT process. LINC00882 was highly expressed in CRC tissues and cell lines. Knockdown of LINC00882 hindered the process of CRC. Studies on gain-of-function and loss-of-function further testified that knockdown of LINC00882 or up-regulation of miR-3619-5p hindered cell migration and EMT process in CRC cells. Moreover, rescue assay proved that the inhibition of migration ability and EMT process resulted from LINC00882 silencing could be rescued when miR-3619-5p inhibitor or pcDNA3.1/CTNNB1 was transfected into CRC cells. Our data suggested that LINC00882 promoted the progression of CRC as a ceRNA to regulate CTNNB1 via sponging miR-3619-5p. This finding would supply a novel insight for CRC therapy. [Display omitted] [ABSTRACT FROM AUTHOR]