Hepatocyte-derived exosomes deliver the lncRNA CYTOR to hepatic stellate cells and promote liver fibrosis.

Liver fibrosis is characterized by the activation and transformation of hepatic stellate cells (HSCs) induced by various injury factors. The degree of liver fibrosis can be significantly improved, but persistent injury factors present a significant therapeutic challenge. Hepatocytes are the most important parenchymal cell type in the liver. In this study, we explored the molecular mechanisms by which damaged liver cells activate HSCs through extracellular vesicles. We established a coculture model of LO2 and LX2 and validated its exosomal transmission activity. Subsequently, differentially expressed long noncoding RNAs (lncRNAs) were screened through RNA sequencing and their mechanisms of action as competing endogenous RNAs (ceRNAs) further confirmed using biological methods, such as FISH and luciferase assays. Damaged liver cells induced activation of LX2 and upregulation of liver fibrosis-related markers. Exosomes extracted and identified from the supernatant fraction contained differentially expressed lncRNA cytoskeleton regulator RNA (CYTOR) that competed with microRNA-125 (miR-125) for binding to glial cell line-derived neurotrophic factor (GDNF) in HSCs, in turn, promoting LX2 activation. MiR-125 could target and regulate both CYTOR and GDNF and vice versa, as verified using the luciferase assay. In an in vivo model, damaged liver extracellular vesicles induced the formation of liver fibrosis. Notably, downregulation of CYTOR within extracellular vesicles effectively inhibited liver fibrosis. The lncRNA CYTOR in exosomes of damaged liver cells is upregulated and modulates the expression of downstream GDNF through activity as a ceRNA, providing an effective mechanism for activation of HSCs.

Silencing of OGDHL promotes liver cancer metastasis by enhancing hypoxia inducible factor 1 α protein stability.

Hepatocellular carcinoma (HCC) is one of the most common malignant diseases associated with a high rate of mortality. Frequent intrahepatic spread, extrahepatic metastasis, and tumor invasiveness are the main factors responsible for the poor prognosis of patients with HCC. Hypoxia-inducible factor 1 (HIF-1) has been verified to play a critical role in the metastasis of HCC. HIFs are also known to be modulated by small molecular metabolites, thus highlighting the need to understand the complexity of their cellular regulation in tumor metastasis. In this study, lower expression levels of oxoglutarate dehydrogenase-like (OGDHL) were strongly correlated with aggressive clinicopathologic characteristics, such as metastasis and invasion in three independent cohorts featuring a total of 281 postoperative HCC patients. The aberrant expression of OGDHL reduced cell invasiveness and migration in vitro and HCC metastasis in vivo, whereas the silencing of OGDHL promoted these processes in HCC cells. The pro-metastatic role of OGDHL downregulation is most likely attributed to its upregulation of HIF-1α transactivation activity and the protein stabilization by promoting the accumulation of L-2-HG to prevent the activity of HIF-1α prolyl hydroxylases, which subsequently causes an epithelial-mesenchymal transition process in HCC cells. These results demonstrate that OGDHL is a dominant factor that modulates the metastasis of HCC.

Alleviation of hepatic fibrosis and autophagy via inhibition of transforming growth factor-ß1/Smads pathway through shikonin.

BACKGROUND AND AIM: Liver fibrosis is a worldwide clinical challenge during the progression of chronic liver disease to liver cirrhosis. Shikonin is extracted from the root of Lithospermum erythrorhizon with antioxidant, anti-inflammatory, anticancer, and wound-healing properties. The study aims to investigate the protective effect of shikonin on liver fibrosis and its underlying mechanism. METHODS: Two liver fibrosis models were established in male C57 mice by intraperitoneal injection of CCl4 or bile duct ligation. Shikonin was administered orally three times weekly at a dose of 2.5 or 5 mg/kg. Protein and mRNA expressions were assayed by quantitative real-time polymerase chain reaction, Western blotting, and immunohistochemical staining. RESULTS: Shikonin significantly inhibited activation of hepatic stellate cells and extracellular matrix formation by downregulating the transforming growth factor-ß1 expression and maintaining the normal balance between metalloproteinase-2 and tissue inhibitor of metalloproteinase-1. Shikonin also decreased hepatic stellate cell energy production by inhibiting autophagy. CONCLUSIONS: The results confirmed that shikonin attenuated liver fibrosis by downregulating the transforming growth factor-ß1/Smads pathway and inhibiting autophagy.

Synthesis and structure-activity relationship studies of MI-2 analogues as MALT1 inhibitors.

Recent studies revealed that MALT1 is a promising therapeutic target for the treatment of ABC-DLBCL. Among several reported MALT1 inhibitors, MI-2 as an irreversible inhibitor represents a new class of ABC-DLBCL therapeutics. Due to its inherent potential cross-reactivity, further structure-activity relationship (SAR) study is imperative. In this work, five focused compound libraries based on the chemical structure of MI-2 are designed and synthesized. The systematic SARs revealed that the side chain of 2-methoxyethoxy has little impact on the activity and can be replaced by other functionalized groups, providing new MI-2 analogues with retained or enhanced potency. Compounds 81-83 with terminal hydroxyl group as side chain displayed enhanced activities against MALT1. Replacement of triazole core with pyrazole is also tolerant, while structural modifications on other sites are detrimental. These findings will facilitate further development of small-molecule MALT1 inhibitors.

By inhibiting PFKFB3, aspirin overcomes sorafenib resistance in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the few cancers with a continuous increase in incidence and mortality. Drug resistance is a major problem in the treatment of HCC. In this study, two sorafenib-resistant HCC cell lines and a nude mouse subcutaneously tumor model were used to explore the possible mechanisms leading to sorafenib resistance, and to investigate whether aspirin could increase the sensitivity of hepatoma cells to sorafenib. The combination of aspirin and sorafenib resulted in a synergistic antitumor effect against liver tumors both in vitro and in vivo. High glycolysis and PFKFB3 overexpression occupied a dominant position in sorafenib resistance, and can be targeted and overcome by aspirin. Aspirin plus sorafenib induced apoptosis in tumors without inducing weight loss, hepatotoxicity or inflammation. Our results suggest that aspirin overcomes sorafenib resistance and their combination may be an effective treatment approach for HCC.

Genistein suppresses aerobic glycolysis and induces hepatocellular carcinoma cell death.

BACKGROUND: Genistein is a natural isoflavone with many health benefits, including antitumour effects. Increased hypoxia-inducible factor 1 α (HIF-1α) levels and glycolysis in tumour cells are associated with an increased risk of mortality, cancer progression, and resistance to therapy. However, the effect of genistein on HIF-1α and glycolysis in hepatocellular carcinoma (HCC) is still unclear. METHODS: Cell viability, apoptosis rate, lactate production, and glucose uptake were measured in HCC cell lines with genistein incubation. Lentivirus-expressed glucose transporter 1 (GLUT1) or/and hexokinase 2 (HK2) and siRNA of HIF-1α were used to test the direct target of genistein. Subcutaneous xenograft mouse models were used to measure in vivo efficacy of genistein and its combination with sorafenib. RESULTS: Genistein inhibited aerobic glycolysis and induced mitochondrial apoptosis in HCC cells. Neither inhibitors nor overexpression of HK2 or GLUTs enhance or alleviate this effect. Although stabiliser of HIF-1α reversed the effect of genistein, genistein no longer has effects on HIF-1α siRNA knockdown HCC cells. In addition, genistein enhanced the antitumour effect of sorafenib in sorafenib-resistant HCC cells and HCC-bearing mice. CONCLUSIONS: Genistein sensitised aerobic glycolytic HCC cells to apoptosis by directly downregulating HIF-1α, therefore inactivating GLUT1 and HK2 to suppress aerobic glycolysis. The inhibitory effect of genistein on tumour cell growth and glycolysis may help identify effective treatments for HCC patients at advanced stages.

Downregulation of UBAP2L Inhibits the Epithelial-Mesenchymal Transition via SNAIL1 Regulation in Hepatocellular Carcinoma Cells.

BACKGROUND/AIMS: Dysregulation of ubiquitin-associated protein 2-like (UBAP2L) has been reported in tumors, but its role in hepatocellular carcinoma (HCC) progression is unclear. METHODS: The expression levels of UBAP2L in HCC tissues and HCC cell lines were detected by western blot and quantitative real-time (qRT) PCR. The effects of UBAP2L expression on HCC cell biological traits, including migration and invasion, were investigated by wound healing assay and matrigel transwell assay. Simultaneously, the expression of epithelial-mesenchymal transition (EMT) markers including E-cadherin, CK-18, N-cadherin, Vimentin, Claudin7 and the promoter activity of E-cadherin were detected by western blot and qRT-PCR. Subsequently, role of SNAIL1 in UBAP2L-mediated EMT and the mechanism underlying UBAP2L-mediated SNAIL1 expression were further investigated. RESULTS: UBAP2L was overexpressed in human HCC tissues compared with peri-tumoral tissues. Downregulation of UBAP2L inhibited migration, invasion and the EMT in highly metastatic HCC cell lines. Furthermore, UBAP2L knockdown inhibited expression of the transcriptional repressor SNAIL1 and its ability to bind to the E-cadherin promoter via SMAD2 signaling pathway, which in turn resulted in increased E-cadherin expression. Additionally, bioinformatics analysis showed that expression of UBAP2L is correlated with poor prognosis in patients with HCC. CONCLUSIONS: UBAP2L plays a critical role in maintenance of the metastatic ability of HCC cells via SNAIL1 Regulation and is predictive of a poor clinical outcome.

Systematic analysis of glutamine metabolism family genes and exploration of the biological role of GPT in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is a malignancy of the digestive system with high incidence rate and mortality, and reliable diagnostic and prognostic markers for CRC are still lacking. Glutamine metabolism is crucial to the occurrence and development of CRC. However, no research has systematically analyzed the biological role of glutamine metabolism-related genes (GMRGs) in CRC. METHODS: We downloaded gene expression data and clinical data of CRC patients from the TCGA database. The UCSC database downloads pan-cancer gene expression data and prognosis data. Characteristic GMRGs were screened out using differential analysis and two types of machine learning (SVM-REF and RandomForest). Single-cell RNA-sequencing data from CRC patients were downloaded from GEO data. ROC curve was used to evaluate the diagnostic value. Kaplan-Meier method and univariate Cox regression analysis were used to evaluate the prognostic value. The oncopredict package is used to calculate IC50 values for common drugs in CRC patients. RESULTS: A total of 31 differentially expressed GMRGs were identified, 9 of which were identified as characteristic GMRGs. Further evaluation of diagnostic and prognostic value finally identified GPT as the most important GMRGs in CRC. scRNA-seq analysis revealed that GPT is almost exclusively expressed in epithelial cells. GPT expression is closely related to the tumor microenvironment and can effectively distinguish the sensitivity of different CRC patients to clinical drugs. In addition, pan-cancer analysis showed that GPT is an excellent diagnostic and prognostic marker for multiple cancers. CONCLUSIONS: GPT is a reliable diagnostic, prognostic marker and therapeutic target in CRC.

A syndrome featuring developmental disorder of the nervous system induced by a novel mutation in the TCF20 gene, rarely concurrent immune disorders: a case report.

Background: The expression of TCF20 is the most widespread in brain tissue. TCF20 depletion or mutation can affect the proliferation and differentiation of embryonic neurons, leading to developmental disorder of the central nervous system and subsequent rare syndrome featuring. Case presentation: Here, we report a 3-year-old boy carrying a novel frameshift mutation in TCF20, c.1839_1872del (p.Met613IlefsTer159), resulting in multisystem disease. In addition to symptoms of neurodevelopmental disorder, a large head circumference, special appearance, overgrowth, abnormal testicular descent. Remarkably, previously infrequently reported symptoms of the immune system such as hyperimmunoglobulinemia E (hyper-IgE), immune thrombocytopenic purpura, cows milk protein allergy, and wheezy bronchitis, were observed. Conclusion: This study broadens the mutation spectrum of the TCF20 and the phenotypic spectrum of TCF20-associated disease.

Fucoidan Ameliorates Ferroptosis in Ischemia-reperfusion-induced Liver Injury through Nrf2/HO-1/GPX4 Activation.

Background and Aims: Liver ischemia-reperfusion (IR) injury is a common pathological process in liver surgery. Ferroptosis, which is closely related to lipid peroxidation, has recently been confirmed to be involved in the pathogenesis of IR injury. However, the development of drugs that regulate ferroptosis has been slow, and a complete understanding of the mechanisms underlying ferroptosis has not yet been achieved. Fucoidan (Fu) is a sulfated polysaccharide that has attracted research interest due to its advantages of easy access and wide biological activity. Methods: In this study, we established models of IR injury using erastin as an activator of ferroptosis, with the ferroptosis inhibitor ferrostatin-1 (Fer-1) as the control. We clarified the molecular mechanism of fucoidan in IR-induced ferroptosis by determining lipid peroxidation levels, mitochondrial morphology, and key pathways in theta were involved. Results: Ferroptosis was closely related to IR-induced hepatocyte injury. The use of fucoidan or Fer-1 inhibited ferroptosis by eliminating reactive oxygen species and inhibiting lipid peroxidation and iron accumulation, while those effects were reversed after treatment with erastin. Iron accumulation, mitochondrial membrane rupture, and active oxygen generation related to ferroptosis also inhibited the entry of nuclear factor erythroid 2-related factor 2 (Nrf2) into the nucleus and reduced downstream heme oxygenase-1 (HO-1) and glutathione peroxidase 4 (GPX4) protein levels. However, fucoidan pretreatment produced adaptive changes that reduced irreversible cell damage induced by IR or erastin. Conclusions: Fucoidan inhibited ferroptosis in liver IR injury via the Nrf2/HO-1/GPX4 axis.

A multicentre study on the clinical characteristics of newborns infected with coronavirus disease 2019 during the omicron wave.

Objective: To investigate the clinical characteristics and outcomes of newborns infected with coronavirus disease 2019 (COVID-19) during the Omicron wave. Methods: From December 1, 2022, to January 4, 2023, clinical data were collected from neonates with COVID-19 who were admitted to 10 hospitals in Foshan City, China. Their epidemiological histories, clinical manifestations and outcomes were analysed. The neonates were divided into symptomatic and asymptomatic groups. The t test or χ2 test was used for comparisons between groups. Results: A total of 286 children were diagnosed, including 166 males, 120 females, 273 full-term infants and 13 premature infants. They were 5.5 (0-30) days old on average when they were admitted to the hospital. These children had contact with patients who tested positive for COVID-19 and were infected through horizontal transmission. This study included 33 asymptomatic and 253 symptomatic patients, among whom 143 were diagnosed with upper respiratory tract infections and 110 were diagnosed with pneumonia. There were no severe or critical patients. Fever (220 patients) was the most common clinical manifestation, with a duration of 1.1 (1-6) days. The next most common clinical manifestations were cough with nasal congestion or runny nose (4 patients), cough (34 patients), poor appetite (7 patients), shortness of breath (15 patients), and poor general status (1 patient). There were no significant abnormalities in routine blood tests among the neonates infected with COVID-19 except for mononucleosis. However, compared with the asymptomatic group, in the symptomatic group, the leukocyte and neutrophil granulocyte counts were significantly decreased, and the monocyte count was significantly increased. C-reactive protein (CRP) levels were significantly increased (≥10 mg/L) in 9 patients. Myocardial enzyme, liver function, kidney function and other tests showed no obvious abnormalities. Conclusions: In this study, neonates infected with the Omicron variant were asymptomatic or had mild disease. Symptomatic patients had lower leucocyte and neutrophil levels than asymptomatic patients.

Ultrastructure of three Species of Entomoneis (Bacillariophyta) from Lake Qinghai of China, with reference to the external areola occlusions.

Three sympatric Entomoneis species, found at the same specific locality in Lake Qinghai, China, are studied by using light and scanning electron microscope. Two species are proposed as new to science and named as E.sinensis sp. nov. and E.qinghainensis sp. nov. The third species is identified as E.paludosa (W. Smith) Reimer. Entomoneissinensis has a linear-lanceolate valve outline and Ƨ-shaped keel, bears two distinct 8-shaped loops formed by the valvocopula pars media in each cell and each of its stria is composed of either a long hymen strip or a long hymen strip plus one separated areola close to the raphe. Its hymen strip belongs to Type Two, which is a siliceous membrane strip perforated by two rows of linear pores next to transapical costae and two rows of rounded pores between these two rows of linear pores. Entomoneisqinghainensis has large cells, very high keel and evident hymen strip regions like a U-shaped neck pillow at the middle of valve face. Its hymen strip belongs to Type One, which is a siliceous membrane strip perforated by irregularly distributed round pores. Entomoneispaludosa also has the hymen strip regions that are worm-like and close to the raphe canal. Its hymen strip is same as that of E.qinghainensis. The two kinds of the outside areola occlusions in Entomoneis are compared, summarised and discussed.

Factors Affecting Adenoma Risk Level in Patients with Intestinal Polyp and Association Analysis.

OBJECTIVE: To explore the factors affecting the adenoma risk level in patients with intestinal polyp and association. METHODS: The clinical data of 3,911 patients with intestinal polyp treated in our hospital from January 2018 to January 2021 were retrospectively analyzed, all patients accepted the histopathological examination, their risk of suffering from adenoma was evaluated according to the results of pathological diagnosis, and relevant hazard factors affecting adenoma risk level in them were analyzed by multifactor logistic regression analysis. RESULTS: The results of multifactor logistic analysis showed that male gender, age ≥60 years, number of polyps >3, diameter ≥2 cm, onset at colon, and physiologically tubulovillous adenoma were the hazard factors causing high-grade adenoma risk in patients with intestinal polyp. CONCLUSION: There are many risk factors causing high-grade adenoma in patients with intestinal polyp, and therefore, the screening for high-risk population shall be enhanced to reduce the potential of carcinomatous change in such patients.

Two new freshwater species of Surirella (Bacillariophyta) from the Wuling Mountains, China.

Two sympatric Surirella species found at the same specific locality in the Wuling Mountains of China are documented with light and scanning electron microscope. Both species are new to science and named S.wufluminensis sp. nov. and S.suiningensis sp. nov. Surirellawufluminensis has large frustules that are either clockwise or counterclockwise twisted when viewed with the light microscope, and possesses distinctive fibulae, mound-like outgrowths on the valve surface throughout, raised longitudinal ridges on both sides of the raphe, and two helictoglossa-like processes at one apex internally. Surirellasuiningensis has narrowly ovate valve outline, distinctive fibulae, troughs alternating with crests from pole to pole, and two helictoglossa-like processes at one apex internally. These two species do not produce costae on the valve surface in contrast to many species in Surirella. This study provides a further two examples of the wide range of morphological diversity in the genus Surirella.

Cord blood antimicrobial peptide LL37 levels in preterm neonates and association with preterm complications.

BACKGROUND: Cathelicidin/LL-37 plays a significant role in the human immune defense reaction. Preterm human immature organs being exposed to inflammation-induced injury was the critical denominator leading to the common preterm associated complications. Previous study showed LL37 concentration in preterm neonates was lower in tracheal aspirates and breast milk as compared to term infants. An adults study showed decreased LL-37 levels was a risk factor for patients in developing severe chronic obstructive pulmonary disease (COPD). However, little is known about the regulation of human cord blood LL37 in preterm neonates and the association with preterm complications. This study was designed to investigate the concentration of LL37 in cord blood of preterm infants and correlation with preterm complications. METHODS: Singleton infants born in June 2017 to August 2021 in the study hospital were enrolled. Maternal and neonatal clinical characteristics were collected. LL37 levels, pro-inflammatory factor interleukin-6 (IL-6) and tumor necrosis factor-a (TNF-a) in cord blood and LL37 levels in serum 48-72 hours after birth were measured by enzyme-linked immunosorbent assay. The serum level of LL37 in preterm and term neonates were compared, the perinatal factors possibly affecting the LL37 levels were investigated and the relationship between LL37 level and preterm outcomes were analyzed. RESULTS: Cord blood LL37 levels in preterm infants were lower than that in term neonates. Cord blood LL37 level was positively correlated with gestational age in preterm. Prenatal steroid administration in preterm neonates decreased cord blood LL37 level. LL37 level was obviously lower in patients with bronchopulmonary dysplasia (BPD). Multiple line regression analysis showed higher LL37 level in cord blood was an independent protective factor for BPD. The concentration of pro-inflammatory factor IL-6 was negatively correlated with LL37. CONCLUSION: Cord blood LL37 levels increased during gestation and decreased after perinatal steroid usage. Very preterm infants who displayed higher cord blood LL37 level had reduced risk of developing BPD. Regulation of pro-inflammatory cytokine IL-6 may be associated with the protective effect of LL37 on BPD.

Resveratrol inhibits proliferation and induces apoptosis through the hedgehog signaling pathway in pancreatic cancer cell.

PURPOSE: To investigate the effect and possible mechanisms of resveratrol on pancreatic cancer cells in vitro. METHODS: After being treated with resveratrol, cell viability, cell cycle phase distribution and apoptosis rate of pancreatic cancer cells were measured by CCK-8 assay and flow cytometer, respectively. The effects of resveratrol on the Hedgehog pathway were studied by real-time RT-PCR and Western blotting. By interfering Gli1 expression in PANC-1 cells and overexpressing Gli1 in BxPC-3 cells, we detected the expressions of Gli1-targeted genes, such as Ptc1, CCND1 and BCL-2, compared with resveratrol experimental group. We further used the luciferase reporter assay to explore the correlation between resveratrol and Gli1. RESULTS: Resveratrol inhibited the growth of pancreatic cancer cells in a dose- and time-dependent manner. Compared with control group, the cells in the G0/G1 phase and the apoptosis rate were significantly increased. Low concentration of resveratrol decreased the expression of the Hedgehog pathway members including Gli1, Ptc1 and Smo. The expression of downstream target genes of the Hedgehog pathway such as Gli1, Ptc1, CCND1 and BCL-2 were significantly decreased after 12.5 µM resveratrol treatment, which demonstrated a similar change of gene expression when Gli1 was knocked down by the RNAi technique in PANC-1 cells. Resveratrol also downregulated the expression of Gli1, Ptc1, CCND1 and BCL-2 in Gli1-overexpressed BxPC-3 cells. Results of the luciferase assay showed that resveratrol did not act on the Gli1 promoter directly. CONCLUSION: Resveratrol can inhibit pancreatic cancer cell survival and its mechanisms might be partly via the Hedgehog signaling pathway. and IAP.

Increased expression of cellular repressor of E1A-stimulated gene (CREG) in gastric cancer patients: a mechanism of proliferation and metastasis in cancer.

BACKGROUND: The cellular repressor of E1A-stimulated genes (CREG), a secreted glycoprotein, has been studied with human embryonic carcinoma cells, vascular smooth muscle cells, and NIH3T3 fibroblasts. However, its relationship to tumor cell proliferation and metastasis has not been examined in human gastric cancers (GC) until now. AIM: To investigate the expression of CREG in GC and its association with GC cell proliferation and metastasis. METHODS: Forty-two cases of GCs, matched normal gastric tissues, and the human gastric cancer cell lines BGC-823, SGC-7901, MKN45, normal gastric mucosa cell line GES, and HUVEC cell line ECV304 were used to analyze CREG expression at the level of mRNA and protein. The expression of CREG was then further examined by immunohistochemistry in 42 GC tissues, and the correlation between the level of CREG and the pathological and clinical data was evaluated. Finally, we down-regulated the expression of CREG in GC cells with specific siRNA, and assessed the role of CREG in the proliferation and metastasis/invasion of the GC cell line. RESULTS: The level of CREG was found to be higher in malignant GC tissues and cells compared to adjacent normal tissues and normal gastric cells (p < 0.001). Additionally, the expression levels of CREG were positively correlated with tumor clinical stage (p = 0.001), tumor metastasis (p < 0.001), and stages of tumor infiltration (p = 0.019). Furthermore, by using siRNA, we found that the down-regulated expression of CREG inhibited the proliferation of GC cells (p < 0.05), and migration of both GC cells (p = 0.001). CONCLUSIONS: Our data suggest that CREG plays an important role in gastric cancer cell proliferation and metastasis and that CREG may be a potential therapeutic target for GC.

A duodenal ampullary tumor with malignant transformation of papillary polyps: a case report and literature review.

Periampullary carcinoma refers to a malignant tumor within 2 cm of the duodenal ampulla. Primary ampullary carcinoma is very rare, accounting for only 0.2% of malignant gastrointestinal tumors. The small intestine accounts for 75% of the length of the gastrointestinal tract, and primary tumors in the small intestine account for only 2% of all gastrointestinal tumors. Here, we report the case of a duodenal ampullary tumor with malignant transformation of parapapillary polyps. The patient had both a primary ampullary tumor and high-grade intraepithelial neoplasia of juxtapapillary adenomatous duodenal polyps.

Construction of Bisindolines via Oxidative Coupling Cyclization.

Herein, we report a general approach for the efficient construction of three-dimensional bisindolines via oxidative coupling cyclization in an intermolecular manner. This reaction is featured by its operational simplicity, metal-free conditions, lack of protecting group, and high selectivity. Notably, a wide range of anilines are suitable in this intermolecular cyclization, furnishing corresponding bisindolines in up to 98% yield.

Long Noncoding RNA (lncRNA) MT1JP Suppresses Hepatocellular Carcinoma (HCC) in vitro.

INTRODUCTION: The purpose of this study was to evaluate the effects and mechanisms of the long noncoding RNA (lncRNA) MT1JP on hepatocellular carcinoma (HCC) in vitro. PATIENTS AND METHODS: Thirty pairs of tumor and adjacent normal tissues were collected from HCC patients. Tissue pathology and MT1JP expression were evaluated by hematoxylin and eosin staining and in situ hybridization (ISH), respectively. The correlation between MT1JP and HCC prognosis was investigated. MTT assays, cloning, flow cytometry, transwell assays, and wound-healing assays were used to evaluate the effects of MT1JP on HCC cell lines. RT-qPCR and Western blot were used to measure the relative mRNA and protein expression levels. RESULTS: The expression of MT1JP was downregulated in HCC tumor tissues compared with that in adjacent normal tissues, while the percent survival was significantly greater in the high MT1JP expression group than in the low MT1JP expression group (P=0.0238). In vitro, overexpression of MT1JP suppressed the proliferation, invasion, and migration, reduced colony cell number, increased cell apoptosis, and induced G1-phase cell cycle arrest in Bel-7402 and Huh-7 cells. Meanwhile, the mRNA and protein expression levels of RUNX3 and P21 were significantly upregulated, whereas those of MMP2 and MMP9 were significantly downregulated, in Bel-7402 and Huh-7 cells overexpressing MT1JP (all P<0.001). CONCLUSION: LncRNA MT1JP may function as a tumor suppressor in HCC. Overexpression of MT1JP suppressed HCC cell biological activities through the regulation of RUNX3.