Length-controlled hydrophobic CF3-COF as a highly efficient absorbent coating for dual-mode solid-phase microextraction of sixteen polycyclic aromatic hydrocarbons in water samples.

Polycyclic aromatic hydrocarbons (PAHs), a group of seriously hazardous environmental contaminants, have attracted extensive attention due to their carcinogenicity, genotoxicity, mutagenicity, and ubiquity. In this work, the excellent hydrophobic trifluoromethyl-enriched covalent organic framework (CF3-COF) was designed and synthesized as coating of solid-phase microextraction (SPME). The CF3-COF offered a high adsorption selectivity for PAHs, which could be attributed to the multiple interactions between the CF3-COF and PAHs, including hydrophobicity interaction, π-π and H bond interactions. Furthermore, headspace (HS) and direct immersion (DI) dual-mode solid-phase microextraction (HS/DI-SPME) were innovatively integrated as a dual-mode extraction by varying the length of SPME coating on stainless-steel, which could simultaneously and efficiently extract 16 PAHs with different volatile. Amazingly, the proposed strategy achieved fast adsorption for PAHs and shortened the adsorption equilibrium time to 15 min. By further integrating with gas chromatography tandem mass spectrometry (GC-MS/MS), PAHs could be detected in the range of 0.008-0.16 ng mL-1 with a quantitative limit of 0.029-0.47 ng mL-1, respectively. The recoveries of PAHs in water samples ranged from 80.84 to 117.67 %. This work indicates that the dual-mode CF3-COF-SPME is a promising candidate for the enrichment of multiple hazardous substances in complicated samples.

Analysis of the efficacy of sleeve gastrectomy, one-anastomosis gastric bypass, and single-anastomosis sleeve ileal bypass in the treatment of metabolic syndrome.

The objective of this study was to evaluate and compare the effectiveness of three different types of bariatric surgeries, namely, sleeve gastrectomy (SG), one-anastomotic gastric bypass (OAGB), and single anastomosis sleeve ileal (SASI) bypass, in the treatment of metabolic syndrome (MS). The optimal approach for managing MS remains uncertain, and thus this study aimed to provide a recent analysis of the efficacy of these surgical procedures. This retrospective study evaluated data of individuals who underwent SG, OAGB, and SASI bypass. The primary outcome measures included weight, body mass index (BMI), glucolipid metabolic index, and the occurrence of treatment-related complications within 6 to 12 months post-surgery. A total of 324 patients were included in this study. Of these, 264 patients underwent SG, 30 underwent OAGB, and 30 underwent SASI bypass. A significant decrease in weight was observed at the 6-month and 12-month marks following all three surgical procedures. Of these, patients who underwent SASI bypass exhibited the greatest reduction in weight and BMI post-surgery. Furthermore, the SASI bypass was associated with a significantly higher percentage of total weight loss (%TWL) and excess body mass index loss (%EBMIL) compared to SG and OAGB. Patients who underwent OAGB and SASI bypass demonstrated notable improvements in type 2 diabetes mellitus (T2DM). Patients who underwent SASI bypass and OAGB experienced greater postoperative comfort and reported fewer complaints of discomfort compared to the other procedure. Based on the retrospective analysis of the data, SASI bypass was associated with greater reductions in weight and BMI, higher percentages of %TWL and %EBMIL, and better improvement in T2DM compared to SG and OAGB. Therefore, both SASI bypass and OAGB were found to be more effective than SG in the treatment of MS.

Short C-terminal Musashi-1 proteins regulate pluripotency states in embryonic stem cells.

The RNA-binding protein Musashi-1 (MSI1) regulates the proliferation and differentiation of adult stem cells. However, its role in embryonic stem cells (ESCs) and early embryonic development remains poorly understood. Here, we report the presence of short C-terminal MSI1 (MSI1-C) proteins in early mouse embryos and mouse ESCs, but not in human ESCs, under conventional culture conditions. In mouse embryos and mESCs, deletion of MSI1-C together with full-length MSI1 causes early embryonic developmental arrest and pluripotency dissolution. MSI1-C is induced upon naive induction and facilitates hESC naive pluripotency acquisition, elevating the pluripotency of primed hESCs toward a formative-like state. MSI1-C proteins are nuclear localized and bind to RNAs involved in DNA-damage repair (including MLH1, BRCA1, and MSH2), conferring on hESCs better survival in human-mouse interspecies cell competition and prolonged ability to form blastoids. This study identifies MSI1-C as an essential regulator in ESC pluripotency states and early embryonic development.

Lipidomic study and diagnosis of hepatocellular carcinoma tumor with rapid evaporative ionization mass spectrometry.

Liver cancer is generally considered the leading cause of cancer deaths worldwide, and hepatocellular carcinoma (HCC) contributes to more than 90% of liver cancers. The altered lipid metabolism for rapid cancer cell growth and tumor formation has been frequently proven. In this study, an ambient ionization mass spectrometry technique, rapid evaporative ionization mass spectrometry (REIMS) using a monopolar electric knife, called iKnife, was systematically optimized and employed for ex vivo analysis of 12 human HCC tumor tissue specimens together with the paired paracancerous tissue (PT) and noncancerous liver tissue (NCT) specimens. Nine free fatty acids and 34 phospholipids were tentatively identified according to their extract masses and/or tandem mass spectra. With the help of statistical methods, 7 free fatty acids and 10 phospholipids were distributed differently in 3 types of liver tissue specimens (95% confidence interval). The box plots showed these characterized lipid metabolites varied in PT, HCC, and NCT. Compared with PT and NCT, the upregulations of four common fatty acids FA 18:0, FA 20:4, FA 16:0, and FA 18:1, together with phospholipids PC 36:1, PE 38:3, PE (18:0/20:4), PA (O-36:1), PC (32:1), PC 32:0, PE 34:0, and PC (16:0/18:1), were found in HCC specimens. The sensitivity and specificity of the established statistic model for real-time HCC tumor diagnosis were 100% and 90.5%, respectively. This study demonstrated that the described REIMS technique is a potential method for rapid lipidomic analysis and characterization of HCC tumor tissue.

Surgery for Cronkhite-Canada syndrome complicated with intussusception: A case report and review of literature.

BACKGROUND: Cronkhite-Canada syndrome (CCS) is a rare nonhereditary disease with a syndrome of multiple gastrointestinal polyps, skin pigmentation, hair loss, and fingernail/toenail dystrophy. Intussusception is a serious condition with an occurrence rate of 5% in adults, which is mainly caused by intestinal tumors or other intestinal occupations. CASE SUMMARY: A 57-year-old woman was admitted to our hospital due to abdominal distension and pain for the past year. Her nausea and vomiting symptoms had been aggravated for the past month. Previous transoral enteroscopy results one year prior showed chronic erosive gastritis protuberans, duodenitis, and jejunitis. She had sparse body hair and brown pigmentation on the skin of her hands and bilateral anterior tibias. The nails of both hands were pale and lacked luster, and the fingernail of her ring finger was longitudinally cracked. Gastroscopy showed extensive diffuse polypoid lump changes in the gastric body and antrum, of 0.5-3 cm in size. Colonoscopy showed multiple polypoid mucosal bulges in the terminal ileum and multiple polyps (0.3-5 cm) throughout the colon. The patient was diagnosed with CCS and underwent partial excision of the polyps, but she refused hormone therapy. One month later, the patient complained of nausea and vomiting, accompanied by abdominal pain and inability to pass gas or stool. Contrast-enhanced computed tomography of the abdomen showed gastrointestinal polyposis and ileocecal intussusception. She underwent stomach and bowel surgery. CONCLUSION: CCS, as a rare disease with poor prognosis, should be treated aggressively. Systematic steroids, immunosuppressive agents, and biological agents were not applied; thus, the patient's symptoms quickly progressed, and intussusception occurred. She had to undergo surgery. Improved compliance may lead to a better prognosis.

Characteristics and potential malignancy of colorectal juvenile polyps in adults: a single-center retrospective study in China.

BACKGROUND: Colorectal juvenile polyps are rare and generally considered benign in adults. Carcinogenesis or neoplastic changes are rarely mentioned in the literature. We systematically evaluated the characteristics and potential malignancy of colorectal juvenile polyps in adults. METHODS: We retrospectively reviewed the medical records of 103 adults diagnosed with colorectal juvenile polyps from September 2007 to May 2020 at our hospital. The characteristics, endoscopic findings, occurrence of intraepithelial neoplasia, carcinogenesis and diagnostic value of chicken skin mucosa (CSM) were analyzed. RESULTS: The average age of patients with juvenile polyps was 43.2 years (range, 19 to 78 years). A total of 101 patients (101/103, 98.1%) had a single juvenile polyp, and two patients had multiple polyps (107 polyps in total). Polyp sizes ranged from 0.5 to 5 cm. One (1/107, 0.9%) juvenile polyp was cancerous, and 7 (7/107, 6.5%) developed low-grade intraepithelial neoplasia. Neoplasia and cancerization did not appear in the two patients with multiple polyps. A 27-year-old female had a 2-cm polyp with well-differentiated adenocarcinoma in the mucosa in the sigmoid colon with erosion on the surface. CSM was observed adjacent to 17 polyps, which were all located in the rectum and sigmoid colon, and one polyp showed low-grade intraepithelial neoplasia. CONCLUSIONS: Colorectal juvenile polyps occur in a wide range of locations and in variable sizes and numbers. These polyps are solitary in most patients and have neoplastic potential. CSM is not a tumorigenic marker in colorectal juvenile polyps and usually occurs in the distant colorectum. Colorectal juvenile polyps in adults may progress from low-grade intraepithelial neoplasia to high-grade intraepithelial neoplasia and then to carcinoma and should be treated when discovered and regularly followed as colorectal adenomas.

Reinforced education by short message service improves the quality of bowel preparation for colonoscopy.

PURPOSE: This study aimed to evaluate the effect of reinforced education (RE) by short message service (SMS) on the bowel preparation quality of patients undergoing colonoscopy. METHODS: Randomized controlled trials (RCTs), conducted on the effect of RE by SMS on bowel preparation for colonoscopy from inception to November 1, 2021, were queried from databases, including PubMed, Web of Science, the Cochrane Library, and EMBASE. After extracting the data, meta-analysis was conducted using Review Manager Software version 5.3. RESULTS: A total of seven RCTs with 5889 patients were subjected to meta-analysis. The rate of adequate bowel preparation in the SMS group (81.7%) was significantly higher than that in the control group (75.7%) (RR: 1.10, 95% CI: 1.03-1.17, p < 0.01). Four studies suggested that RE by SMS significantly reduced the non-attendance rate of patients for scheduled colonoscopy (RR: 0.74, 95% CI: 0.56-0.99, p < 0.05). CONCLUSION: RE by SMS for patients undergoing colonoscopy can significantly improve the quality of bowel preparation and decrease the non-attendance rate of patients for scheduled colonoscopy.

Idiopathic mesenteric phlebosclerosis associated with long-term oral intake of geniposide.

BACKGROUND: Idiopathic mesenteric phlebosclerosis (IMP) is a rare disease, and its etiology and risk factors remain uncertain. AIM: To investigate the possible influence of Chinese herbal liquid containing geniposide on IMP. METHODS: The detailed formula of herbal liquid prescriptions of all patients was studied, and the herbal ingredients were compared to identify the toxic agent as a possible etiological factor. Abdominal computed tomography (CT) and colonoscopy images were reviewed to determine the extent and severity of mesenteric phlebosclerosis and the presence of findings regarding colitis. The disease CT score was determined by the distribution of mesenteric vein calcification and colon wall thickening on CT images. The drinking index of medicinal liquor was calculated from the daily quantity and drinking years of Chinese medicinal liquor. Subsequently, Spearman's correlation analysis was conducted to evaluate the correlation between the drinking index and the CT disease score. RESULTS: The mean age of the 8 enrolled patients was 75.7 years and male predominance was found (all 8 patients were men). The patients had histories of 5-40 years of oral Chinese herbal liquids containing geniposide and exhibited typical imaging characteristics (e.g., threadlike calcifications along the colonic and mesenteric vessels or associated with a thickened colonic wall in CT images). Calcifications were confined to the right-side mesenteric vein in 6 of the 8 patients (75%) and involved the left-side mesenteric vein of 2 cases (25%) and the calcifications extended to the mesorectum in 1 of them. The thickening of colon wall mainly occurred in the right colon and the transverse colon. The median disease CT score was 4.88 (n = 7) and the median drinking index was 5680 (n = 7). After Spearman's correlation analysis, the median CT score of the disease showed a significant positive correlation with the median drinking index (r = 0.842, P < 0.05). CONCLUSION: Long-term oral intake of Chinese herbal liquid containing geniposide may play a role in the pathogenesis of IMP.

Roles and mechanisms of NRG1 in modulating the pathogenesis of NAFLD through ErbB3 signaling in hepatocytes (NRG1 modulates NAFLD through ErbB3 signaling).

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is an emerging chronic liver disease. However, the underlying mechanisms remained poorly understood. Neuregulin (NRG) family participate in energy metabolism, and might be related to NAFLD. METHODS: L02 cells were exposed to oleic acid to establish a cellular model of NAFLD. We analyzed the NAFLD cells with NRG1 and subsequent ErbB3 siRNA treatment. Cellular total lipid was stained by Oil Red O, while triglyceride content and inflammation markers were measured by enzymatic kits. The expressions of down-stream molecules were evaluated by western blot. RESULTS: In vitro, NRG1 could alleviate the steatosis of NAFLD, and inhibit the expression of IL-6 and TNF-α. The downregulation of ErbB3 aggravated steatosis, improved the levels of triglyceride, IL-6 and TNF-α in NRG1-treated NAFLD. Moreover, NRG1 treatment up-regulated ErbB3 phosphorylation, and increased the expression of PI3K and phosphorylation-AKT. When NRG1-treated NAFLD cells were transfected with ErbB3 siRNA, the expressions of ErbB3, p-ErbB3, p-AKT and PI3K were all reduced. CONCLUSION: NRG1 might play a protective role in the pathogenesis of NAFLD through ErbB3 phosphorylation to modulate the activation of PI3K-AKT pathway. The findings will expand the understanding of the mechanisms of NAFLD, and provide potential therapeutic targets.

Poorer prognosis for neuroendocrine carcinoma than signet ring cell cancer of the colon and rectum (CRC-NEC): a propensity score matching analysis of patients from the Surveillance, Epidemiology, and End Results (SEER) database.

PURPOSE: Colorectal neuroendocrine carcinomas (CRC-NECs) are rare, comprising < 1% of colorectal cancers. This study aimed to assess the incidence, clinicopathologic characteristics, prognostic factors, and treatment outcomes of CRC-NEC. METHODS: We analysed the Surveillance, Epidemiology, and End Results (SEER) database to identify patients from 20 to 74 years old diagnosed with CRC-NEC or common CRC (non-NEC) during 2004-2013. Log-rank testing was conducted to assess survival differences. A competing-risks regression model was used to adjust for covariate effects in the propensity score-matched (PSM) cohort, and adjusted hazard ratios (HRs) were calculated for the raw and PSM cohorts. RESULTS: We identified 67,484 patients (344 CRC-NEC and 67,140 non-NEC). Lymph node metastasis (LNM) was more common in CRC-NEC (75.29%, n = 259) than in non-NEC (51.53%, n = 34,600) (P < 0.001); 56.40% (n = 194) of CRC-NECs were located on the right side, while 18.31% (n = 63) were located on the left side, with a statistically significant difference in distribution (P < 0.001) compared to that in non-NEC CRC. Multivariate analysis indicated that a left-side location was an independent adverse prognostic factor for CRC-NEC (P = 0.043). CRC-NEC had the poorest cancer-specific survival (median CSS, 9.0 months) among assessed cancers, even poorer than that of signet ring cell cancer (median CSS, 24.0 months). However, both radical operation (P = 0.007) and chemotherapy (P = 0.008) were beneficial for CSS. CONCLUSION: NEC is a rare and extremely aggressive tumour with a poor prognosis. Right-side NEC has a better prognosis than left-side NEC. Early diagnosis, radical surgery, and chemotherapy are imperative for improving survival.

Multifocal gastrointestinal epithelioid angiosarcomas diagnosed by endoscopic mucosal resection: A case report.

BACKGROUND: Epithelioid angiosarcoma is a vascular neoplasm that is among the most aggressive subtypes of sarcomas. Its involvement in the gastrointestinal tract is rare. We here report a case of multifocal gastrointestinal epithelioid angiosarcomas presenting with gastrointestinal bleeding. CASE SUMMARY: A 77-year-old woman was admitted because of melena and dizziness for three months. Gastroscopy and colonoscopy were performed, revealing a centrally ulcerated hemorrhagic polypoid lesion in the gastric body and multiple polypoid lesions with blood clots and hemorrhagic tendency in the colon. Histopathological examination of routine endoscopic biopsy samples showed inflammation in the gastric mucosa and tubular adenomas in the colon. The polypoid lesions were removed by endoscopic mucosal resection. Immunohistochemistry suggested a final diagnosis of epithelioid angiosarcomas. The patient refused chemotherapy and died after three months. CONCLUSION: Epithelioid angiosarcomas are characterized by highly vascular nature and tendency to cause gastrointestinal bleeding. Efforts to obtain histological findings using endoscopic mucosal resection are of great importance.

Diagnosis and management of a solitary colorectal juvenile polyp in an adult during follow-up for ulcerative colitis: A case report.

BACKGROUND: Juvenile polyps are the most common type of polyps in children but are rare in adults. Inflammatory bowel disease (IBD) patients have a similar spectrum of symptoms as patients with juvenile polyps. Both patients with juvenile polyps and those with active IBD have high fecal calprotectin levels. Four cases of children with ulcerative colitis (UC) with solitary juvenile polyps and one case of an adult with UC with juvenile polyposis syndrome have been reported upon diagnosis of UC, while there have been no cases of adults with UC with solitary juvenile polyp reported in the literature. CASE SUMMARY: A 37-year-old man with a 12-year history of UC was admitted to our clinic because of increased stool frequency. UC was diagnosed at the age of 25. As the lesion was confined to the rectum, sulfasalazine suppositories or mesalazine suppositories were used. The patient was followed in an outpatient clinic, and colonoscopy was performed every one or two years. The latest examination was undertaken three years prior in the presence of proctitis. Recently, the patient complained of three to five bowel movements a day. There was mucus in the stool but no visible blood. Colonoscopy revealed a solitary polyp, about 1.5 cm in diameter, with a short and broad peduncle in the transverse colon surrounded by congestive and edematous mucosa. The patient had no family history of colorectal polyps or cancer. The polyp was successfully removed by endoscopic mucosal resection. Histopathological examination revealed that the polyp was a juvenile polyp without any malignant signs. Immunohistochemical staining for p53 showed wild-type expression and p53 overexpression was not detected. Ki-67 labeling index was 3%. CONCLUSION: This is the first case of an adult UC patient with a solitary juvenile polyp at the 12-year follow-up. The correlation between juvenile polyps and the activity of IBD needs further study.

Synchronous colonic mucosa-associated lymphoid tissue lymphoma found after surgery for adenocarcinoma: A case report and review of literature.

BACKGROUND: Mucosa-associated lymphoid tissue (MALT) lymphoma is a subtype of non-Hodgkin lymphoma that is mainly involved in the gastrointestinal tract. The synchronous occurrence of colonic MALT lymphoma and adenocarcinoma in the same patient is extremely rare. We here report a case of synchronous colonic MALT lymphoma found on surveillance colonoscopy five months after surgery and chemotherapy for sigmoid adenocarcinoma. CASE SUMMARY: A 67-year-old man was admitted because of hematochezia for two months. Colonoscopy suggested a colonic tumor before hospitalization. Abdominal computed tomography (CT) revealed local thickening of the sigmoid colon. The patient underwent a left hemicolectomy with local lymph node dissection. The histopathology revealed moderately differentiated adenocarcinoma and partially mucinous adenocarcinoma. The pTNM stage was T3N1Mx. The patient received chemotherapy with six cycles of mFOLFOX6 after surgery. Colonoscopy was performed five months later and revealed single, flat, polypoid lesions of the colon 33 cm away from the anus. Subsequently, the patient underwent endoscopic mucosal resection for further diagnosis. The pathological diagnosis was MALT lymphoma. Positron emission tomography /CT suggested metastasis. The patient refused further treatment and died ten months later. CONCLUSION: Colonic MALT lymphoma may occur after surgery and chemotherapy for adenocarcinoma as a synchronous malignancy. Regular surveillance colonoscopy and careful monitoring after surgery are critical.

Targeting EphA2 with miR-124 mediates Erlotinib resistance in K-RAS mutated pancreatic cancer.

OBJECTIVES: Chemotheraputic drug resistance is a critical factor associated with the poor survival in advanced/metastatic pancreatic cancer (PC) patients. METHODS: Human pancreatic cell lines Capan-1 and BXPC-3 were cultured with different concentrations of erlotinib (0, 10, 50, and 100 µm) for 48 h. The relative cell viability and apoptosis was detected using MTT assays and flow cytometry apoptosis analysis, respectively. Transfection of pcDNA-EphA2, si-EphA2 and miR-124 mimic/inhibitor was used to modulate the intracellular level of EphA2 and miR-124. The interaction between miR-124 and the 3'UTR of EphA2 was explored using dual luciferase reporter assay. KEY FINDINGS: Compared with BXPC-3 cells, Capan-1 cells showed resistance to differential concentration treatment of erlotinib. The expression of EphA-2 was significantly increased and the expression of miR-124 was significantly decreased in Capan-1 cells. Overexpressing EphA2 induced resistance of BXPC-3 cells to erlotinib treatment. And EphA2 was identified as a novel target gene for miR-124. MiR-124 overexpression was able to sensitize the response of Capan-1 cells to erlotinib through inhibiting EphA2. Furthermore, both miR-124 overexpression and EphA2 inhibition sensitized Capan-1 cells to erlotinib in xenograft model. CONCLUSIONS: Our study demonstrated that EphA2 rescued by miR-124 downregulation conferred the erlotinib resistance of PC cell Capan-1 with K-RAS mutation.

SET alpha and SET beta mRNA isoforms in chronic lymphocytic leukaemia.

Alteration in RNA splicing is implicated in carcinogenesis and progression. Mutations in spliceosome genes and alternative splicing of other genes have been noted in chronic lymphocytic leukaemia (CLL), a common B cell malignancy with heterogeneous outcomes. We previously demonstrated that differences in the amount of SET oncoprotein (a physiological inhibitor of the serine/threonine phosphatase, PP2A) is associated with clinical aggressiveness in patients with CLL. It is unknown if alternative splicing of gene transcripts regulating kinases and phosphatases affects disease pathobiology and CLL progression. We show here for the first time that mRNA levels of the alternatively spliced SET isoforms, SETA and SETB (SETα and SETß), significantly correlate with disease severity (overall survival and time-to-first-treatment) in CLL patients. In addition, we demonstrate that relative increase of SETA to SETB mRNA can discriminate patients with a more aggressive disease course within the otherwise favourable CLL risk classifications of IGHV mutated and favourable hierarchical fluorescence in situ hybridisation groups. We validate our finding by showing comparable relationships of SET mRNA with disease outcomes using samples from an independent CLL cohort from a separate institution. These findings indicate that alternative splicing of SET, and potentially other signalling cascade molecules, influences CLL biology and patient outcomes.

Diagnostic challenges in differentiating intramural gastric abscess from gastric cancer: Two case reports.

RATIONALE: Intramural gastric abscess is a rare clinical condition. It is frequently neglected because of the absence of specific clinical symptoms and misdiagnosed due to the difficulty in differentiating a benign lesion from a malignant one on the gastric wall. Several imaging techniques are helpful for identifying an intramural gastric abscess. Nevertheless, a definite diagnosis is still challenging, and unnecessary surgery is sometimes performed. Therefore, more information regarding case experiences should be shared to help correctly diagnose intramural gastric abscesses. PATIENT CONCERNS: Two patients, a 47-year-old woman and a 31-year-old man, were hospitalized for abdominal pain. DIAGNOSIS AND INTERVENTIONS: In addition to routine blood tests, either two or three imaging examinations, including esophagogastroduodenoscopy (EGD), computed tomography (CT), and endoscopic ultrasonography (EUS), were performed for these patients. The first patient was diagnosed with gastric cancer metastasized to the gastrocolic ligament, and the other was suspected to have a gastric wall abscess secondary to cancer of unknown origin. Both patients underwent surgery. OURCOMES: Surgery revealed a gastric wall abscess involving the colon in the first patient. She recovered after using oral antibiotics for 1 week, and she showed no discomfort or abnormalities during follow-up examinations. The second patient was diagnosed with gastric wall abscess derived from metastasized gastric cancer with a primary tumor located at the splenic flexure of the colon. He was discharged because of intolerance to chemotherapy and died before follow-up. LESSONS: EGD, CT, and EUS/fine-needle aspiration (EUS/FNA) are extremely valuable for differentiating an intramural gastric abscess from gastric cancer, and misdiagnoses can occur if any of these assessments is ignored. Hence, we recommend performing EGD, CT, and EUS/FNA as part of the routine examination when either of these two diseases is suspected clinically.

IL-8 regulates the doxorubicin resistance of colorectal cancer cells via modulation of multidrug resistance 1 (MDR1).

Cytokines play important roles in tumorigenesis and progression of cancer cells, while their functions in drug resistance remain to be illustrated. We successfully generated doxorubicin (Dox)-resistant CRC HCT-116 and SW480 cells (namely HCT-116/Dox and SW480/Dox, respectively). Cytokine expression analysis revealed that IL-8, while not FGF-2, EGF, TGF-ß, IL-6, or IL-10, was significantly increased in Dox-resistant CRC cells as compared with their corresponding parental cells. Targeted inhibition of IL-8 via siRNAs or its inhibitor reparixin can increase the Dox sensitivity of HCT-116/Dox and SW480/Dox cells. The si-IL-8 can decrease the mRNA and protein expression of multidrug resistance 1 (MDR1, encoded by ABCB1), while has no effect on the expression of multidrug resistance-associated protein 1 (ABCC1), in CRC Dox-resistant cells. IL-8 can increase the phosphorylation of p65 and then upregulate the binding between p65 and promoter of ABCB1. BAY 11-7082, the inhibitor of NF-κB, suppressed the recombination IL-8 (rIL-8) induced upregulation of ABCB1. It confirmed that NF-κB is involved in IL-8-induced upregulation of ABCB1. rIL-8 also increased the phosphorylation of IKK-ß, which can further activate NF-κB, while specific inhibitor of IKK-ß (ACHP) can reverse rIL-8-induced phosphorylation of p65 and upregulation of MDR1. These results suggested that IL-8 regulates the Dox resistance of CRC cells via modulation of MDR1 through IKK-ß/p65 signals. The targeted inhibition of IL-8 might be an important potential approach to overcome the clinical Dox resistance in CRC patients.

Sustained Delivery Growth Factors with Polyethyleneimine-Modified Nanoparticles Promote Embryonic Stem Cells Differentiation and Liver Regeneration.

Stem-cell-derived hepatocyte transplantation is considered as a potential method for the therapy of acute and chronic liver failure. However, the low efficiency of differentiation into mature and functional hepatocytes remains a major challenge for clinical applications. By using polyethyleneimine-modified silica nanoparticles, this study develops a system for sustained delivery of growth factors, leading to induce hepatocyte-like cells (iHeps) from mouse embryonic stem cells (mESCs) and improve the expression of endoderm and hepatocyte-specific genes and proteins significantly, thus producing a higher population of functional hepatocytes in vitro. When transplanted into liver-injured mice after four weeks, mESC-derived definitive endoderm cells treated with this delivery system show higher integration efficiency into the host liver, differentiated into iHeps in vivo and significantly restored the injured liver. Therefore, these findings reveal the multiple advantages of functionalized nanoparticles to serve as efficient delivery platforms to promote stem cell differentiation in the regenerative medicine.

Human RAD6 promotes G1-S transition and cell proliferation through upregulation of cyclin D1 expression.

Protein ubiquitinylation regulates protein stability and activity. RAD6, an E2 ubiquitin-conjugating enzyme, which that has been substantially biochemically characterized, functions in a number of biologically relevant pathways, including cell cycle progression. In this study, we show that RAD6 promotes the G1-S transition and cell proliferation by regulating the expression of cyclin D1 (CCND1) in human cells. Furthermore, our data indicate that RAD6 influences the transcription of CCND1 by increasing monoubiquitinylation of histone H2B and trimethylation of H3K4 in the CCND1 promoter region. Our study presents, for the first time, an evidence for the function of RAD6 in cell cycle progression and cell proliferation in human cells, raising the possibility that RAD6 could be a new target for molecular diagnosis and prognosis in cancer therapeutics.

Neutrophils with myeloid derived suppressor function deplete arginine and constrain T cell function in septic shock patients.

INTRODUCTION: Impaired T cell function in sepsis is associated with poor outcome, but the mechanisms are unclear. In cancer, arginase-expressing myeloid derived suppressor cells (MDSCs) deplete arginine, impair T cell receptor CD3 zeta-chain expression and T cell function and are linked to poor clinical outcome, but their role during acute human infectious disease and in particular sepsis remains unknown. Hypoarginemia is prevalent in sepsis. This study aimed to determine whether neutrophils that co-purify with PBMC express arginase, and if arginine depletion constrains T cell CD3 zeta-chain expression and function in human sepsis. METHODS: Using flow cytometry, cell culture, HPLC, arginase activity and mRNA detection, our study examined whether neutrophils, with reduced buoyant density isolated in the Ficoll interface, metabolise L-arginine and suppress T cell proliferation in sepsis. A total of 35 sepsis patients (23 with septic shock) and 12 hospital controls in a tertiary referral hospital in tropical Australia were evaluated. RESULTS: Only sepsis patients had interphase neutrophils, neutrophils co-purifying with mononuclear cells (≤1.077 specific gravity). The percentage of interphase neutrophils in sepsis was proportional to sepsis severity and correlated with plasma IL-6 concentrations. Ex vivo, sepsis-derived interphase neutrophils expressed arginase, metabolised culture L-arginine and suppressed T cell proliferation and CD3 zeta-chain expression. In vivo, in septic shock there was a longitudinal inverse association between interphase neutrophil number and CD3 zeta-chain expression. Depletion or inhibition of interphase neutrophils in vitro restored zeta-chain expression and T cell function. CONCLUSIONS: For the first time during an acute human infection, interphase neutrophils that express arginase were found to circulate in sepsis, in proportion to disease severity. These neutrophil-MDSCs impair T cell CD3 zeta-chain expression and T cell function via L-arginine metabolism, and likely contribute to the T cell dysfunction seen in sepsis. Modulation of neutrophil-MDSC or their downstream effects warrant consideration as targets for novel adjunctive therapies in sepsis.