Research progress of brain organoids in the field of diabetes.

Human embryonic stem cells and human induced pluripotent stem cells may be used to create 3D tissues called brain organoids. They duplicate the physiological and pathological characteristics of human brain tissue more faithfully in terms of both structure and function, and they more precisely resemble the morphology and cellular structure of the human embryonic brain. This makes them valuable models for both drug screening and in vitro studies on the development of the human brain and associated disorders. The technical breakthroughs enabled by brain organoids have a significant impact on the research of different brain regions, brain development and sickness, the connections between the brain and other tissues and organs, and brain evolution. This article discusses the development of brain organoids, their use in diabetes research, and their progress.

Mesenchymal stem cells overexpressing XIST induce macrophage M2 polarization and improve neural stem cell homeostatic microenvironment, alleviating spinal cord injury.

Spinal cord injury (SCI) is a significant cause of disability worldwide, with limited treatment options. This study investigated the potential of bone marrow-derived mesenchymal stem cells (BMSCs) modified with XIST lentiviral vector to modulate macrophage polarization and affect neural stem cell (NSC) microenvironment reconstruction following SCI. Bioinformatics analysis revealed that MID1 might be crucial for BMSCs' treatment of SCI. XIST overexpression enriched Zmynd8 to the promoter region of MID1 and inhibited MID1 transcription, which promoted macrophage M2 polarization. In vitro experiments showed that BMSCs-XIST promoted NSC proliferation, migration, differentiation, and axonal growth by inducing macrophage M2 polarization, suppressing inflammation, and accelerating the re-establishment of the homeostatic microenvironment of NSCs. In vivo, animal experiments confirmed that BMSCs-XIST significantly alleviated SCI by promoting NSC differentiation and axon formation in the injured area. The study demonstrated the potential of XIST-overexpressing BMSCs for treating SCI by regulating macrophage polarization and homeostasis of the NSC microenvironment. These findings provide new insights into the development of stem cell-based therapies for SCI.

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.

Association between hypokalemia and small bowel capsule endoscopy completion rates in patients in South China: A prospective single-center study.

BACKGROUND/AIMS: Approximately 20-30% of small bowel capsule endoscopies (SBCEs) do not reach the cecum at the completion of the examination. We aimed to determine whether hypokalemia influences the completion rate and small bowel transit time (SBTT) of SBCE. PATIENTS AND METHODS: From January to December 2017, 112 patients (18-75 years old) who underwent SBCE were assessed consecutively for enrolment in our study. On the day of the procedure, a blood test was performed prior to capsule ingestion. The completion rate, gastric transit time (GTT), SBTT, and diagnostic yield were recorded for each SBCE. RESULTS: The SBCE completion rate was lower in the hypokalemia group than that in the normal potassium group (55.6% (15/27) vs. 76.5% (65/85), P = 0.036). The median GTT was 55.5 ± 47.1 min in the hypokalemia group and 46.7 ± 44.5 min in the normal potassium group (P > 0.05). The median SBTT was 412.8 ± 123.3 min in the hypokalemia group and 367.3 ± 172.5 min in the normal potassium group (P > 0.05). The diagnostic yields of the hypokalemia and normal potassium groups were 74.1% and 78.8%, respectively (P = 1.00). CONCLUSION: Hypokalemia may decrease the SBCE completion rate. Physicians should consider the possibility of hypokalemia after bowel preparation because this condition is not rare. Potassium deficiencies should be rectified prior to performing SBCE procedures to increase the SBCE completion rate.

Facile Solvothermal Preparation of Mn2CuO4 Microspheres: Excellent Electrocatalyst for Real-Time Detection of H2O2 Released from Live Cells.

Hydrogen peroxide (H2O2) is an eminent biomarker in pathogenesis; a selective, highly sensitive real-time detection of H2O2 released from live cells has drawn a significant research interest in bioanalytical chemistry. Binary transition-metal oxides (BTMOs) displayed a recognizable benefit in enhancing the sensitivity of H2O2 detection; although the reported BTMO-based H2O2 sensor's detection limit is still insufficient, it is not appropriate for in situ profiling of trace amounts of cellular H2O2. In this paper, we describe an efficient, reliable electrochemical biosensor based on Mn2CuO4 (MCO) microspheres to assay cellular H2O2. The Mn2CuO4 microspheres were prepared through a superficial solvothermal method. It is obvious from impedance studies, introduction of manganese into copper oxide lattice significantly improved the ionic conductivity, which is beneficial for the electrochemical sensing process. Thanks to the distinct microsphere structure and excellent synergy, MCO-modified electrode exhibited excellent nonenzymatic electrochemical behavior toward H2O2 sensing. The MCO-modified electrode delivered a broad working range (36 nM to 9.3 mM) and an appreciable detection limit (13 nM), with high selectivity toward H2O2. To prove its practicality, the developed sensor was applied in the detection of cellular H2O2 released by RAW 264.7 cells in presence of CHAPS. These results label the possible appliance of the sensor in clinical analysis and pathophysiology. Thus, BTMOs are evolving as a promising candidate in designing catalytic matrices for biosensor applications.

Efficacy of two different dosages of levofloxacin in curing Helicobacter pylori infection: A Prospective, Single-Center, randomized clinical trial.

Bismuth + proton pump inhibitor (PPI) + amoxicillin + levofloxacin is one of the bismuth quadruple therapy regimens widely used for the eradication of H. pylori infection. The recommended dosage of levofloxacin is 500 mg once daily or 200 mg twice daily to eradicate H. pylori infection. The aim of the present open-label, randomized control trial was to compare the effectiveness, safety, and compliance of different dosages of levofloxacin used to cure Helicobacter pylori infection. Eligible patients were randomly assigned to receive esomeprazole, amoxicillin, colloidal bismuth pectin and levofloxacin 500 mg once/day (group A) or levofloxacin 200 mg twice/day (group B) for 14 days. The primary outcome was the eradication rates in the intention-to-treat (ITT) and per protocol (PP) analyses. Overall, 400 patients were enrolled. The eradication rates in group A and group B were 77.5% and 79.5% respectively, in the ITT analysis, and 82.9% and 86.4%, respectively, in the PP analysis. No significant differences were found between two groups in terms of eradication rate, adverse effects or compliance. Oral levofloxacin 200 mg twice daily was similar in efficacy for eradicating H. pylori infection to oral levofloxacin 500 mg once daily but with lower mean total costs.

Three-dimensional plotted alginate fibers embedded with diclofenac and bone cells coated with chitosan for bone regeneration during inflammation.

Alginate hydrogel fibers embedded with bone cells and diclofenac were coated with a layer of chitosan hydrogel and made into a porous scaffold by three-dimensional (3D) printing for drug release and bone regeneration. It was hypothesized that the chitosan coating could improve the scaffold's drug retention and release properties and biocompatibility. Macrophage cells were stimulated and cocultured with the scaffold. Tests were conducted to show how the chitosan coating affected the scaffold's drug release efficacy and how the release efficacy affected the cellular activities of stimulated macrophages and bone cells. The bone cells encapsulated in the coated scaffold demonstrated good viability after the acidic/basic coating process. The coating improved the retention and release efficacy of diclofenac and hence significantly inhibited interleukin-6 and tumor necrosis factor-α secretion from macrophages (p < 0.05). The bone cells in the coated sample mineralized more extensively than the control (p < 0.01). They also more actively expressed genes that produce proteins for extracellular matrix remodeling, MMP13, and interacting with the mineral matrix, OPN (both p < 0.01). It is believed that on days 7 and 10, when diclofenac was depleted and the concentrations of inflammatory compounds surged, the coating effectively blocked the harmful compounds and protected the bone cells within the fibers. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1511-1521, 2018.

H. pylori-encoded CagA disrupts tight junctions and induces invasiveness of AGS gastric carcinoma cells via Cdx2-dependent targeting of Claudin-2.

Helicobacter pylori encoded CagA is presently the only known virulence factor that is injected into gastric epithelial cells where it destroys apical junctional complexes and induces dedifferentiation of gastric epithelial cells, leading to H. pylori-related gastric carcinogensis. However, little is known about the molecular mechanisms by which CagA mediates these changes. Caudal-related homeobox 2 (Cdx2) is an intestine-specific transcription factor highly expressed in multistage tissues of dysplasia and cancer. One specific target of Cdx2, Claudin-2, is involved in the regulation of tight junction (TJ) permeability. In this study, our findings showed that the activity of Cdx2 binding to Cdx binding sites of CdxA (GTTTATG) and CdxB (TTTTAGG) of probes corresponding to claudin-2 flanking region increased in AGS cells, infected with CagA positive wild-type strain of H. pylori, compared to CagA negative isogenic mutant-type strain. Moreover, Cdx2 upregulated claudin-2 expression at transcriptional level and translational level. In the meantime, we found that TJs of AGS cells, infected with CagA positive wild-type strain of H. pylori, compared to CagA negative isogenic mutant-type strain, were more severely destroyed, leading to wider cell gap, interference of contact, scattering and highly elevated migration of cells. Herein, this study is firstly demonstrated that H. pylori-encoded CagA disrupts TJs and induces invasiveness of AGS gastric carcinoma cells via Cdx2-dependent targeting of Claudin-2. This provides a new mechanism whereby CagA induced dedifferentiation of AGS cells, leading to malignant behavior of biology.

Role of trefoil factor 1 in gastric cancer and relationship between trefoil factor 1 and gastrokine 1.

Trefoil factor 1 (TFF1) is a small cysteine-rich secreted protein which is principally expressed in the superficial cells of gastric mucosa. In gastric cancer, TFF1 is downregulated and plays an important role. Gastrokine 1 (GKN1) is a secreted protein with similar expression and biological functions to TFF1. This study aimed to determine the expression and biological functions of TFF1 and the relationships between TFF1 and GKN1 in gastric cancer. RT-PCR and immunohistochemistry were performed to detect TFF1 expression in gastric cancer cell lines and tissues. The transfected and co-transfected AGS cells which stably expressed TFF1 or both TFF1 and GKN1 were generated. Phenotypic changes such as cell viability, apoptosis and cell cycle modulation were assayed in the transfected cells. We found that TFF1 expression was significantly downregulated or lost in gastric cancer cell lines, gastric dysplasia and cancer. Restoration of TFF1 expression in AGS cells suppressed tumor cell viability and arrested AGS cells in the G1-S transition phase after olomoucine treatment. However, TFF1 was unable to induce cell apoptosis. In co-transfected cells, we found that TFF1 and GKN1 did not directly interact at the protein level. GKN1 was unable to cooperate with TFF1 on cell viability suppression, cell apoptosis and differentiation. Together, these results indicate that TFF1 expression is significantly downregulated in gastric cancer. TFF1 inhibited cell proliferation by delaying G1-S phase transition but not by inducing apoptosis. TFF1 may not interact or cooperate with GKN1 at the protein and functional level.

Helicobacter pylori infection and administration of non-steroidal anti-inflammatory drugs down-regulate the expression of gastrokine-1 in gastric mucosa.

BACKGROUND/AIMS: Gastrokine-1 is a novel protein that plays an important role in the maintenance of the integrity of the gastric mucosa. However, whether Helicobacter pylori infection and non-steroidal anti-inflammatory drugs, which are known to cause gastric mucosal injuries, affect gastrokine-1 expression in the gastric mucosa is unknown. The aim of the present study was to determine gastric mucosal expression of gastrokine-1 in patients with Helicobacter pylori infection or long-term non-steroidal anti-inflammatory drug administration. MATERIAL AND METHODS: A total of 40 patients with functional dyspepsia (20 with Helicobacter pylori-negative chronic gastritis, and 20 with Helicobacter pylori-positive chronic gastritis), and 37 Helicobacter pylori-negative long-term non-steroidal anti-inflammatory drug users (26 with aspirin, 11 with selective cyclooxygenase-2 inhibitors) were selected. In addition, 20 Helicobacter pylori-negative healthy volunteers were recruited as controls. All subjects underwent endoscopies with biopsies taken from the antrum and the sites with lesions. Gastric mucosal changes were detected endoscopically and histologically, and gastrokine-1 protein expression in the antral mucosa was analyzed by immunohistochemistry. RESULTS: Expression of gastrokine-1 protein was decreased in Helicobacter pylori-positive chronic gastritis compared with Helicobacter pylori-negative subjects and the healthy controls. Similarly, gastrokine-1 expression in non-steroidal anti-inflammatory drug users was also decreased, compared with the healthy controls, but there was no significant difference in gastrokine-1 expression between the aspirin group and selective cyclooxygenase-2 inhibitor group. Moreover, gastrokine-1 expression levels tended to be associated with the severity of chronic gastritis. CONCLUSIONS: Both Helicobacter pylori infection and long-term non-steroidal anti-inflammatory drug administration downregulate gastrokine-1 expression in the gastric mucosa, which may contribute to the gastric mucosal injuries induced by these two factors.

[Luminescence properties of Eu, Dy doped BaAl12 O19 long afterglow phosphors].

Long afterglow phosphors BaAl12 O19:Eu2+/Eu3+, Dy3+ were synthesized by high temperature solid state method under different atmosphere. X-ray powder diffraction (XRD) shows that pure BaAl12 O19 phase structure was obtained and the do ping ions Eu2+/Eu3+, Dy3+ didn't change the phase structure. By comparison, the authors found that the doping ions Eu2+/ Eu3+, Dy3+ caused the XRD diffraction peaks moving to the high angle slightly which displayed that the inter-planar spacing was changed via Eu and Dy replacing Ba lattice in BaAl12 O19. Emission spectra show that all the samples prepared under different conditions exhibit the 4f6 5d1 --> 4J7 broadband transition which is the features emission of Eu2+ and the existence of the features emission of Eu2+ in the sample synthesized in air indicates that Eu3+ ions can be reduced to divalent state in air. The doping ions Dy3+ can not only enhance the luminous intensity of samples but also make the samples to obtain long afterglow characteristics. The afterglow decay and thermoluminescence studies of the Eu, Dy co-doped sample synthesized under reducing atmosphere reveal that the sample has good long afterglow properties at room temperature and high temperature.

Downregulation of gastrokine-1 in gastric cancer tissues and restoration of its expression induced gastric cancer cells to apoptosis.

BACKGROUND: Gastrokine-1 (GKN1), a secreted protein, is specifically expressed in gastric mucosa to protect and maintain the integrity of gastric epithelium. The present study investigated differential expression of GKN1 in normal, precancerous, and cancerous gastric tissues, and explored the biological functions of GKN1 protein in gastric cancer cells. METHODS: RT-PCR, Western blot, and immunohistochemistry were performed to detect GKN1 expression in normal, precancerous, cancerous gastric tissues and seven gastric cancer cell lines. Gene transfection was used to restore GKN1 expression in gastric cancer AGS cells. Phenotypic changes (i.e., cell viability, apoptosis, cell cycle modulation, and sensitivity of gastric cancer cells to fluorouracil (5-FU)) were assayed in the transfected cells. DNA microarrays were used to analyze expression changes of apoptosis-related genes. RESULTS: Significant downregulation or absence of GKN1 expression in seven gastric cancer cell lines were detected and progressive decrease of GKN1 expression from normal mucosa, precancerous tissue, to cancer tissues was observed. Moreover, restoration of GKN1 expression suppressed gastric cancer cell viability and induced the cells to undergo apoptosis. GKN1 expression also enhanced tumor cell sensitivity to 5-FU treatment. Moreover, it was found that GKN1 expression in AGS cells modulated expression of 19 apoptosis-related genes. CONCLUSIONS: Expression of GKN1 is progressively lost from normal mucosa, precancerous to cancerous gastric tissues, while restoration of GKN1 expression induces gastric cancer cells to undergo apoptosis, and enhances sensitivity of gastric cancer cells to 5-FU-induced apoptosis.

[Thermoluminescence study on Sr2SiO4 long afterglow material doped with Eu2+].

Sr2SiO4:Eu0.03(2+) phosphors were synthesized through the solid-state reaction technique. The X-ray diffraction shows that the phase of the phosphors is orthorhombic alpha'-Sr2SiO4. The produced phosphors show one intense emission band located at 490 nm. The phosphor shows a long afterglow properties excited by the sunlight. The decay characteristics show that the phosphors consist of a quick decay process and a slow decay process. The experimental results demonstrate that the thermoluminescence (TL) curves of the samples containing four peaks, located at 346, 420, 457 and 552 K, respectively. Meanwhile, the different peaks show the different decay characteristics, and the electron transfer between the trap levels was measured.

A selective requirement for 53BP1 in the biological response to genomic instability induced by Brca1 deficiency.

The molecular pathways leading from genomic instability to cellular senescence and/or cell death remain incompletely characterized. Using mouse embryonic fibroblasts with constitutively increased DNA damage due to the absence of the full-length form of the tumor suppressor Brca1 (Brca1(Delta 11/Delta 11)), we show that deletion of p53 binding protein 1 (53BP1) selectivity abrogates senescence and cell death stimulated by reduced Brca1 activity. Furthermore, the embryonic lethality induced by Brca1 mutation can be alleviated by 53BP1 deletion. Adult Brca1(Delta 11/Delta 11)53BP1(-/-) manifest constitutively high levels of genomic instability, yet age relatively normally, with a surprisingly low incidence of overall tumor formation. Together, these in vitro and in vivo data suggest that 53BP1 is specifically required for the development of premature senescence and apoptosis induced by Brca1 deficiency. These observations may have important implications for Brca1-mediated tumor formation as well as for the molecular pathway leading from genomic instability to organismal aging.

Aryl hydrocarbon receptor pathway activation enhances gastric cancer cell invasiveness likely through a c-Jun-dependent induction of matrix metalloproteinase-9.

BACKGROUND: Abberant aryl hydrocarbon receptor (AhR) expression and AhR pathway activation are involved in gastric carcinogenesis. However, the relationship between AhR pathway activation and gastric cancer progression is still unclear. In present study, we used 2,3,7,8-tetrachlorodibenzo-para-dioxin (TCDD), a classic and most potent ligand of AhR, to activate AhR pathway and investigated the effect of AhR pathway activation on human gastric cancer AGS cell invasion and explored the corresponding mechanism. RESULTS: To determine whether AhR pathway can be activated in AGS cells, we examined the expression of CYP1A1, a classic target gene of AhR pathway, following TCDD exposure. RT-PCR and western blot analysis showed that both CYP1A1 mRNA and protein expression were increased in a dose-dependent manner following TCDD treatment and AhR antagonist resveratrol (RSV) could reverse this TCDD-induced CYP1A1 expression. To determine whether TCDD treatment of AGS cells results in an induction of MMP-9 expression, we detected MMP-9 mRNA using RT-PCR and detected MMP-9 enzymatic activity using gelatin zymography. The results showed that both MMP-9 mRNA expression and enzymatic activity were gradually increased with the concentration increase of TCDD in media and these changes could be reversed by RSV treatment in a dose-dependent manner. To examine whether AhR activation-induced MMP-9 expression and activity in AGS cells results in increased migration and invasion, we performed wound healing migration assay and transwell migration and invasion assay. After TCDD treatment, the migration distance and the migration and invasion abilities of AGS cells were increased with a dose-dependent manner. To demonstrate AhR activation-induced MMP-9 expression is mediated by c-Jun, siRNA transfection was performed to silence c-Jun mRNA in AGS cells. The results showed that MMP-9 mRNA expression and activity in untreated control AGS cells were very weak; After TCDD (10 nmol/L) treatment, MMP-9 mRNA expression and activity were significant increased; This TCDD-induced MMP-9 expression and activity increase could be abolished by c-Jun siRNA transfection. CONCLUSION: AhR pathway activation enhances gastric cancer cell invasiveness likely through a c-Jun-dependent induction of MMP-9. Our results provide insight into the mechanism and function of the AhR pathway and its impact on gastric cancer progression.

Potential therapeutic significance of increased expression of aryl hydrocarbon receptor in human gastric cancer.

AIM: To determine the functional significance of aryl hydrocarbon receptor (AhR) in gastric carcinogenesis, and to explore the possible role of AhR in gastric cancer (GC) treatment. METHODS: RT-PCR, real-time PCR, and Western blotting were performed to detect AhR expression in 39 GC tissues and five GC cell lines. AhR protein was detected by immunohistochemistry (IHC) in 190 samples: 30 chronic superficial gastritis (CSG), 30 chronic atrophic gastritis (CAG), 30 intestinal metaplasia (IM), 30 atypical hyperplasia (AH), and 70 GC. The AhR agonist tetrachlorodibenzo-para-dioxin (TCDD) was used to treat AGS cells. MTT assay and flow cytometric analysis were performed to measure the viability, cell cycle and apoptosis of AGS cells. RESULTS: AhR expression was significantly increased in GC tissues and GC cell lines. IHC results indicated that the levels of AhR expression gradually increased, with the lowest levels in CSG, followed by CAG, IM, AH and GC. AhR expression and nuclear translocation were significantly higher in GC than in precancerous tissues. TCDD inhibited proliferation of AGS cells via induction of growth arrest at the G1-S phase. CONCLUSION: AhR plays an important role in gastric carcinogenesis. AhR may be a potential therapeutic target for GC treatment.

[Study of three-dimensional model on biomechanical characteristics of mandibular fractures in different site].

OBJECTIVE: To determine the biomechanical characteristics of mandibular fractures in different site. METHODS: Nine adult mandibular specimens were measured precisely. The data was used to establish a three-dimensional model. When mandibular was under functional loading, the bending and torsion moment as well as shear force of angle, body and symphyseal fracture was calculated. The data were analyzed by Origin 6.0 software. RESULTS: Angle fracture had relatively high positive bending moment and high shear force. Body fracture had positive as well as negative bending moment and the highest torsion moments. Symphyseal fracture had only negative bending moment and relatively low shear force. CONCLUSION: Angle, body and symphyseal fractures each have a biomechanics characteristic. These biomechanics characteristic should have an important meaning in the treatment of mandibular fractures and instructing patient how to bite correctly.