Unraveling the Mechanism of Curculiginis Rhizoma in Suppressing Cisplatin Resistance in Non-Small Cell Lung Cancer: An Experimental Study.

Introduction: Non-small cell lung cancer (NSCLC) stands as one of the most prevalent malignancies, and chemotherapy remains the primary treatment for advanced stages. However, the high expression of ABC binding cassette transporters, including MRP, P-gp, and LRP, along with multidrug resistance proteins, has been identified as a significant factor contributing to decreased chemotherapy drug sensitivity. This study aims to explore the impact and underlying mechanisms of Curculiginis Rhizoma [Hypoxidaceae; Curculigo orchioides Gaertn.] (CR) in combination with cisplatin on improving chemoresistance mediated by ABC binding cassette transporters and multidrug resistance proteins in NSCLC. Methods and Results: To unravel the relationship between JNK, MRP, P-gp, and LRP in NSCLC and gain insights into the regulatory mechanism of CR, this study employs an integrated approach encompassing bioinformatics, molecular docking, molecular dynamics, animal and cellular experiments. Bioinformatics analysis revealed a significant increase in the expression levels of JNK, MRP, P-gp, and LRP subtypes in multidrug-resistant non-small cell lung cancer. Subsequent animal experiments have shown that the combination of CR with cisplatin can improve the survival rate of lung cancer mice. Molecular docking and molecular dynamics analyses demonstrated favorable binding interactions between curculigoside and the aforementioned subtypes of JNK, MRP, P-gp, and LRP. In cellular experiments, the combination of cisplatin with both curculigoside and CR extract resulted in a notable decrease in cell viability and downregulation of the expression of JNK1, JNK2, MRP1, MRP2, MRP4, P-gp, and LRP1 in A549/cis cells. Conclusion: Remarkably, curculigoside exerted a significant downregulation effect on the expression levels of JNK1, MRP1, MRP2, MRP4, and LRP1. CR, particularly its main effective metabolite, curculigoside, has the potential to enhance the sensitivity of non-small cell lung cancer to cisplatin by regulating levels of JNK/MRP/LRP/P-gp and mitigating multidrug resistance.

Endoscopic treatment of bleeding gastric ulcer causing gastric wall necrosis: A case report.

BACKGROUND: Gastric wall necrosis is a rare complication of endoscopic treatment for bleeding gastric ulcer, which may exacerbate the patient's condition once it occurs and may even require surgical intervention for treatment. CASE SUMMARY: A 59-year-old man was admitted to our department with melena. Endoscopy revealed a giant ulcer in the gastric antrum with a visible vessel in its center, which was treated with sclerosants and tissue glue injection and resulted in necrosis of the gastric wall. CONCLUSION: Injection of sclerosants and tissue glue may lead to gastric wall necrosis, which is a serious complication. Therefore, before administering this treatment to patients, we should consider other more effective methods of hemostasis to avoid gastric wall necrosis.

The perilous consequences of bowel preparation: a case study with literature review of Boerhaave syndrome.

Colonoscopy is widely acknowledged as a prevalent and efficacious approach for the diagnosis and treatment of gastrointestinal disorders. In order to guarantee an effective colonoscopy, it is imperative for patients to undergo an optimal bowel preparation regimen. This entails the consumption of a substantial volume of a non-absorbable solution to comprehensively purge the colon of any fecal residue. Nevertheless, it is noteworthy to acknowledge that the bowel preparation procedure may occasionally elicit adverse symptoms such as nausea and vomiting. In exceptional instances, the occurrence of excessive vomiting may lead to the rupture of the distal esophagus, a grave medical condition referred to as Boerhaave syndrome (BS). Timely identification and efficient intervention are imperative for the management of this infrequent yet potentially perilous ailment. This investigation presents a case study of a patient who developed BS subsequent to the ingestion of mannitol during bowel preparation. Furthermore, an exhaustive examination of extant case reports and pertinent literature on esophageal perforation linked to colonoscopy has been conducted. This analysis provides valuable insights into the prevention, reduction, and treatment of such serious complications.

Programmed Cell Death in Liver Fibrosis.

Programmed cell death (PCD) is a comprehensive term that encompasses various forms of cell death, such as apoptosis, necroptosis, pyroptosis, ferroptosis, and autophagy, which play a crucial role in the pathogenesis of liver fibrosis. PCD facilitates the elimination of aberrant cells, particularly activated hepatic stellate cells (HSCs), which are the primary producers of extracellular matrix (ECM). The removal of HSCs may impede ECM synthesis, thereby mitigating liver fibrosis. As such, PCD has emerged as a promising therapeutic target for the development of novel drugs to treat liver fibrosis. Numerous studies have been conducted to investigate the underlying mechanisms of PCD in the elimination of activated HSCs and other aberrant liver cells in fibrotic liver tissue, including hepatocytes, hepatic sinusoid endothelial cells (LSECs), and Kupffer cells (KCs). The induction of PCD, the interplay between different forms of PCD, and the potential harm or benefit of PCD in liver fibrosis are topics of ongoing research. Evidences suggest that PCD is a complex process with dual effects on liver fibrosis. The purpose of this review is to summarize the most recent advances in PCD and liver fibrosis research.

Endoscopic mucosal resection with double band ligation versus endoscopic submucosal dissection for small rectal neuroendocrine tumors.

BACKGROUND: Endoscopic resection remains an effective method for the treatment of small rectal neuroendocrine tumors (NETs) (≤ 10 mm). Moreover, endoscopic mucosal resection (EMR) with double band ligation (EMR-dB), a simplified modification of EMR with band ligation, is an alternative strategy to remove small rectal NETs. AIM: To evaluate the feasibility and safety of EMR-dB for the treatment of small rectal NETs (≤ 10 mm). METHODS: A total of 50 patients with small rectal NETs, without regional lymph node enlargement or distant metastasis confirmed by endoscopic ultrasound, computerized tomography scan, or magnetic resonance imaging, were enrolled in the study from March 2021 to June 2022. These patients were randomly assigned into the EMR-dB (n = 25) group or endoscopic submucosal dissection (ESD) group (n = 25). The characteristics of the patients and tumors, procedure time, devices cost, complete resection rate, complications, and recurrence outcomes were analyzed. RESULTS: There were 25 patients (13 males, 12 females; age range 28-68 years old) in the EMR-dB group, and the ESD group contained 25 patients (15 males, 10 females; age range 25-70 years old). Both groups had similar lesion sizes (EMR-dB 4.53 ± 1.02 mm, ESD 5.140 ± 1.74 mm; P = 0.141) and resected lesion sizes(1.32 ± 0.52 cm vs 1.58 ± 0.84 cm; P = 0.269). Furthermore, the histological complete resection and en bloc resection rates were achieved in all patients (100% for each). In addition, there was no significant difference in the complication rate between the two groups. However, the procedure time was significantly shorter and the devices cost was significantly lower in the EMR-dB group. Besides, there was no recurrence in both groups during the follow-up period. CONCLUSION: The procedure time of EMR-dB was shorter compared with ESD, and both approaches showed a similar curative effect. Taken together, EMR-dB was a feasible and safe option for the treatment of small rectal NETs.

Exosomal LINC00460/miR-503-5p/ANLN positive feedback loop aggravates pancreatic cancer progression through regulating T cell-mediated cytotoxicity and PD-1 checkpoint.

BACKGROUND: Long non-coding RNA (lncRNA) LINC00460 is an onco-lncRNA in a variety of cancers, including pancreatic cancer (PC). This study is aimed to investigate the regulatory mechanisms of LINC00460 in PC. METHODS: The tumor and adjacent normal tissues were collected from 73 PC patients. The expression of LINC00460, miR-503-5p, and ANLN was detected using qRT-PCR. We then analyzed the proliferation, migration, invasion, and apoptosis/cell cycle of PC cells by performing the MTT/EdU, transwell, and flow cytometry assays, respectively. The xenograft tumor model were utilized to confirm the effect of LINC00460 knockdown on PC through anti-PD-1 therapy in vivo, and the sensitivity of PANC-1 cells to the cytotoxicity of CD8+ T cells in vitro. Western blotting was used to determine the protein levels. A co-culture model was utilized to explore the effects of exosomes on macrophages. RESULTS: LINC00460 was up-regulated in PC tissues and cells. LINC00460 knockdown suppressed cell proliferation, migration, and invasion, facilitated cell apoptosis and G0/G1 phase arrest, and inhibited the tumor growth through anti-PD-1 therapy. Both miR-503-5p down-regulation and ANLN up-regulation reversed the effects of LINC00460 knockdown on inhibiting the proliferation, migration and invasion, and on promoting the apoptosis, G0/G1 phase arrest, and the sensitivity of PC cells to the cytotoxicity of CD8+ T cells. Exosomes were uptaken by the ambient PC cells. PANC-1 cells-derived exosomal LINC00460-induced M2 macrophage polarization accelerates the cell migration and invasion. CONCLUSIONS: LINC00460 silencing attenuates the development of PC by regulating the miR-503-5p/ANLN axis and exosomal LINC00460-induced M2 macrophage polarization accelerates the migration and invasion of PANC-1 cells, thus LINC00460 may act as a possible therapeutic target for treating PC.

The influence of family support during endoscopic submucosal dissection on patient's anxiety.

Background: Psychological problems may promote peptic ulcers. Ulcer-like wounds can be formed after gastric endoscopic submucosal dissection (ESD). The influence of family support on the healing of gastric ESD-induced ulcers remains largely undetermined. Objective: In the present study, we aimed to assess the Hospital Anxiety and Depression Scale (HADS) scores and the incidence of post-ESD complications in patients with family support in the care process and those in the non-relative group. Materials and methods: A total of 191 patients aged between 30 and 70 years who received gastric ESD were evaluated with the Chinese version of HADS. Differences in depression and anxiety between the two groups were compared using the chi-square test and t-test. Multivariable logistic regression models were used to examine whether anxiety and depression were the risk factors for post-ESD complications. Results: The mean values of HADS-A (4.61 ± 2.89 vs. 5.56 ± 3.07, p = 0.042) and HADS-D (4.14 ± 3.03 vs. 4.97 ± 2.61, p = 0.048) scores were significantly lower in patients with accompanying relatives compared with those in the non-relative group. Besides, through the pre-ESD and post-ESD self-contrast, the scores of anxiety and depression in the relative-group were 0.57 and 0.56, respectively (p < 0.001), while those in the non-relative group were increased by 1.43 and 1.49, respectively (p < 0.001). Multivariable logistic regression analysis revealed that HADS-A, HADS-D scores, and age were significantly correlated with post-ESD abdominal pain (P < 0.05). Conclusions: The occurrence and degree of adverse emotions such as psychological anxiety and depression in patients who received gastric ESD with accompanying relatives during hospitalization may were reduced, and the incidence of gastric post-ESD abdominal pain may was also decreased.

Genetic Dissection of Rice Ratooning Ability Using an Introgression Line Population and Substitution Mapping of a Pleiotropic Quantitative Trait Locus qRA5.

Ratooning ability is a key factor that influences ratoon rice yield, in the area where light and temperature are not enough for second season rice. In the present study, an introgression line population derived from Minghui 63 as the recipient parent and 02428 as the donor parent was developed, and a high-density bin map containing 4568 bins was constructed. Nine ratooning-ability-related traits were measured, including maximum tiller number, panicle number, and grain yield per plant in the first season and ratoon season, as well as three secondary traits, maximum tiller number ratio, panicle number ratio, and grain yield ratio. A total of 22 main-effect QTLs were identified and explained for 3.26-18.63% of the phenotypic variations in the introgression line population. Three genomic regions, including 14.12-14.65 Mb on chromosome 5, 4.64-5.76 Mb on chromosome 8, and 10.64-15.52 Mb on chromosome 11, were identified to simultaneously control different ratooning-ability-related traits. Among them, qRA5 in the region of 14.12-14.65 Mb on chromosome 5 was validated for its pleiotropic effects on maximum tiller number and panicle number in the first season, as well as its maximum tiller number ratio, panicle number ratio, and grain yield ratio. Moreover, qRA5 was independent of genetic background and delimited into a 311.16 kb region by a substitution mapping approach. These results will help us better understand the genetic basis of rice ratooning ability and provide a valuable gene resource for breeding high-yield ratoon rice varieties.

Long noncoding RNA KIF9-AS1 promotes cell apoptosis by targeting the microRNA-148a-3p/suppressor of cytokine signaling axis in inflammatory bowel disease.

OBJECTIVE: Inflammatory bowel disease (IBD) is a chronic intestinal disease. This study was attempted to investigate the effects of long noncoding RNA KIF9-AS1 (KIF9-AS1) on the development of IBD and its underlying mechanism of action. METHODS: Quantitative real time PCR (qRT-PCR) was implemented to examine the expression of KIF9-AS1 and microRNA-148a-3p (miR-148a-3p). The IBD mouse model was induced by dextran sulfate sodium (DSS). The body weight, disease activity index (DAI) score, colon length and histological injury were used to evaluate the colon injury. The levels of proinflammatory cytokines were measured by ELISA. In vitro, IBD was simulated by DSS treatment in colonic cells. Then the apoptosis of colonic cells was detected by flow cytometry assay. Furthermore, a dual-luciferase reporter assay was used to demonstrate the interactions among KIF9-AS1, miR-148a-3p and suppressor of cytokine signaling (SOCS3). RESULTS: KIF9-AS1 expression was upregulated in IBD patients, DSS-induced IBD mice and DSS-induced colonic cells, whereas miR-148a-3p expression was downregulated. KIF9-AS1 silencing attenuated the apoptosis of DSS-induced colonic cells in vitro and alleviated colon injury and inflammation in DSS-induced IBD mice in vivo. Additionally, the mechanical experiment confirmed that KIF9-AS1 and SOCS3 were both targeted by miR-148a-3p with the complementary binding sites at 3'UTR. Moreover, miR-148a-3p inhibition or SOCS3 overexpression reversed the suppressive effect of KIF9-AS1 silencing on the apoptosis of DSS-induced colonic cells. CONCLUSION: KIF9-AS1 silencing hampered the colon injury and inflammation in DSS-induced IBD mice in vivo, and restrained the apoptosis of DSS-induced colonic cells by regulating the miR-148a-3p/SOCS3 axis in vitro, providing a new therapeutic target for IBD.

Overlooked risk for needle tract seeding following endoscopic ultrasound-guided minimally invasive tissue acquisition.

Endoscopic ultrasound-guided minimally invasive tissue acquisition can be performed by two approaches as follows: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) and endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB). These have been evolved into leading approaches and widely used for the histological diagnosis of tumors in the gastrointestinal tract and adjacent organs. However, the role of EUS-FNA and EUS-FNB in disease diagnosis and evaluation remains controversial. Although the incidence of surgery-associated complications remains low, the consequences of needle tract seeding can be serious or even life-threatening. Recently, increasing case reports of needle tract seeding are emerging, especially caused by EUS-FNA. This complication needs serious consideration. In the present work, we integrated these case reports and the related literature, and summarized the relevant cases and technical characteristics of needle tract seeding caused by EUS-FNA and EUS-FNB. Collectively, our findings provided valuable insights into the prevention and reduction of such serious complication.

Possible role of microRNA miRNA-IL-25 interaction in mice with ulcerative colitis.

BACKGROUND: The regulatory network of ulcerative colitis (UC)-associated miRNAs is not fully understood. In this study, we aim to investigate the global profile and regulatory network of UC associated miRNAs in the context of dextran sulfate sodium (DSS). METHODS: UC was induced in C57BL mice using DSS. Differentially expressed miRNAs were screened by RNA sequencing and subjected to the Kyoto Encyclopedia of Genes and Genomes Pathway enrichment analysis. RT-qPCR was used to verify the differential expression of miRNAs and candidate target mRNA. Luciferase reporter vector bearing a miRNA binding site was constructed to verify the binding site of the miRNA on mRNA. RESULTS: A total of 95 miRNAs (31 were up-regulated and 64 were down regulated) differentially expressed in the colonic tissues of the UC mice. Among the differentially expressed miRNAs, IL-25 pathway genes were enriched. Subsequent RT-qPCR confirmed a decreased expression of IL-25 and a significant up regulation of IL-25 target miRNAs including mmu-miR-135b-5p, mmu-miR-7239-5p and mmu-miR-691 in UC mice. CONCLUSION: Using the luciferase assay, we verified the biding sites of mmu-miR-135b-5p and mmu-miR-691 to the IL-25 3'UTR. In conclusion, mmu-miR-135b-5p:IL-25 and mmu-miR-691:IL-25 interactions are important pathways that may exert a protective role in UC.

Close homolog of L1-deficient ameliorates inflammatory bowel disease by regulating the balance of Th17/Treg.

OBJECTIVE: The aim of this study is to investigate the role of close homolog of L1 (CHL1) on inflammatory bowel disease (IBD), and the correlation with the balance of Th17/Treg. METHODS: Dextran sodium sulfate (DSS)-induced IBD mice model was established. CHL1 knockout (KO) mice and CHL1 wild-type (WT) mice were subjected to DSS. CHL1 expression was detected using qRT-PCR. Weight was recorded daily, and disease activity index (DAI) score was assessed. The colon length and histological changes were measured. The number of neutrophils, macrophages and T cells was observed by immunohistochemistry. The expression of inflammatory cytokines and the proportion of Th17/Treg cells were detected by qRT-PCR and flow cytometry. The expression of RORγt, STAT3 and Foxp3 was detected by using immunohistochemistry and Western blot. RESULTS: CHL1 expression was upregulated in DSS-induced IBD mice. DSS-CHLl-KO mice exhibited less weight loss than the DSS-CHLl-WT mice. The DAI score and histological score were decreased in DSS-CHLl-KO mice compared with DSS-CHLl-WT mice, while colon length was increased. Number of neutrophils, macrophages and T cells, and expression of TNF-α, IL-6, IL-17A, IL-21 and IL-23 were decreased in DSS-CHLl-KO mice, while IL-10 expression was increased. Moreover, CHL1-deficient inhibited Th17 cells differentiation and promoted Treg cells differentiation in IBD mice. CHL1-deficient also inhibited the expression of RORγt and STAT3, and promoted the expression of Foxp3 in IBD mice. CONCLUSION: CHL1-deficient reduces the inflammatory response by regulating the balance of Th17/Treg in mice with IBD. CHL1 is expected to be a new target for the treatment of IBD.

miR-802 participates in the inflammatory process of inflammatory bowel disease by suppressing SOCS5.

The present study aims to reveal the detailed molecular mechanism of microRNA (miR)-802 in the progression of inflammatory bowel disease (IBD). IBD tissues were obtained from IBD patients, followed by CD4+ cells isolation. Then, qRT-PCR and ELISA were used to detect the expression of miR-802, suppressor of cytokine signaling 5 (SOCS5), interleukin (IL)-17A and tumor necrosis factor (TNF)-α. Transfection of miR-802 mimics and miR-802 inhibitor in CD4+ cells was detected by Western blot. TargetScan and luciferase reporter assay were used to detect the relationship between SOCS5 and miR-802. Finally, colitis mice model was established to verify whether miR-802 inhibitor was involved in the protective effect of colonic mucosa. The miR-802 was highly expressed in inflamed mucosa and PBMC cells of IBD. The highest expression of miR-802 was observed in CD4+ T cells based on different immune cell subsets analysis. SOCS5 was the target gene of miR-802. The mice model experiments showed that blockade of miR-802 could alleviate mice colitis. Our study suggests that up-regulation of miR-802 plays an important role in inflammatory process of IBD via targeting SOCS5. Moreover, the differentiation of Th17 and secretion of TNF-α in IBD could be stimulated by miR-802.