Erratum: [Corrigendum] Cross regulation of signaling pathways in gastrointestinal stromal tumor.

[This corrects the article DOI: 10.3892/ol.2018.9494.].

Oxide-Derived Bismuth as an Efficient Catalyst for Electrochemical Reduction of Flue Gas.

Post-combustion flue gas (mainly containing 5-40% CO2 balanced by N2 ) accounts for about 60% global CO2 emission. Rational conversion of flue gas into value-added chemicals is still a formidable challenge. Herein, this work reports a ß-Bi2 O3 -derived bismuth (OD-Bi) catalyst with surface coordinated oxygen for efficient electroreduction of pure CO2 , N2, and flue gas. During pure CO2 electroreduction, the maximum Faradaic efficiency (FE) of formate reaches 98.0% and stays above 90% in a broad potential of 600 mV with a long-term stability of 50 h. Additionally, OD-Bi achieves an ammonia (NH3 ) FE of 18.53% and yield rate of 11.5 µg h-1 mgcat -1 in pure N2 atmosphere. Noticeably, in simulated flue gas (15% CO2 balanced by N2 with trace impurities), a maximum formate FE of 97.3% is delivered within a flow cell, meanwhile above 90% formate FEs are obtained in a wide potential range of 700 mV. In-situ Raman combined with theory calculations reveals that the surface coordinated oxygen species in OD-Bi can drastically activate CO2 and N2 molecules by selectively favors the adsorption of *OCHO and *NNH intermediates, respectively. This work provides a surface oxygen modulation strategy to develop efficient bismuth-based electrocatalysts for directly reducing commercially relevant flue gas into valuable chemicals.

BNIP3 Upregulation Characterizes Cancer Cell Subpopulation With Increased Fitness and Proliferation.

BNIP3 is a BH3-only protein with both pro-apoptotic and pro-survival roles depending on the cellular context. It remains unclear how BNIP3 RNA level dictates cell fate decisions of cancer cells. Here, we undertook a quantitative analysis of BNIP3 expression and functions in single-cell datasets of various epithelial malignancies. Our results demonstrated that BNIP3 upregulation characterizes cancer cell subpopulations with increased fitness and proliferation. We further validated the upregulation of BNIP3 in liver cancer 3D organoid cultures compared with 2D culture. Taken together, the combination of in silico perturbations using public single-cell datasets and experimental cancer modeling using organoids ushered in a new approach to address cancer heterogeneity.

Biased Random Walk With Restart on Multilayer Heterogeneous Networks for MiRNA-Disease Association Prediction.

Numerous experiments have proved that microRNAs (miRNAs) could be used as diagnostic biomarkers for many complex diseases. Thus, it is conceivable that predicting the unobserved associations between miRNAs and diseases is extremely significant for the medical field. Here, based on heterogeneous networks built on the information of known miRNA-disease associations, miRNA function similarity, disease semantic similarity, and Gaussian interaction profile kernel similarity for miRNAs and diseases, we developed a computing model of biased random walk with restart on multilayer heterogeneous networks for miRNA-disease association prediction (BRWRMHMDA) through enforcing degree-based biased random walk with restart (BRWR). Assessment results reflected that an AUC of 0.8310 was gained in local leave-one-out cross-validation (LOOCV), which proved the calculation algorithm's good performance. Besides, we carried out BRWRMHMDA to prioritize candidate miRNAs for esophageal neoplasms based on HMDD v2.0. We further prioritize candidate miRNAs for breast neoplasms based on HMDD v1.0. The local LOOCV results and performance analysis of the case study all showed that the proposed model has good and stable performance.

Glycogen synthase kinase-3ß promotes radiation-induced lung fibrosis by regulating ß-catenin/lin28 signaling network to determine type II alveolar stem cell transdifferentiation state.

The role of type II alveolar epithelial stem cells (AEC II) for alveolar repair in radiation-induced lung fibrosis (RILF) remains largely unknown, mainly because of AEC II phenotype's spontaneous change in vitro. Cell differentiation status is determined by Lin28 and let-7 miRNAs in see-saw-pattern. Lin28, a repressor of let-7 and a stem cell marker, is activated by ß-catenin. The expression of ß-catenin is regulated by GSK-3ß/TGF-ß1 signaling. To understand the true role of AEC II in RILF, we freshly isolated primary AEC II directly from thoracically irradiated lungs. We then explored the expressions of cell phenotype markers and differentiation regulators in these isolated AEC II to analyze the correlation between GSK-3ß/TGF-ß1/ß-catenin signaling pathway, lin28/let-7 balance, and AEC II phenotypes at different injury phases following irradiation. Results showed that isolated single primary cells displayed AEC II ultrastructural features and proSP-C positive. The gene expressions of prosp-c (an AEC II biomarker) and hopx (an AEC I marker) significantly increased in isolated AEC II during injury repair phase (P < .001 and P < .05) but decreased at end-stage of injury, while mesenchymal markers increased in both isolated AEC II and irradiated lungs. mRNA levels of gsk-3ß, tgf-ß1, and ß-catenin increased in all irradiated AEC II, but more pronounced in the second half of injury phase (P < .05-P < .001). Similarly, the expression of lin28 was also significantly elevated in isolated AEC II at the late phase (P < .05-P < .001). Four let-7 miRNAs were significantly upregulated in all irradiated AEC II groups (P < .05-P < .001). The time-dependent and highly consistent uptrends for four lin28/let-7 ratios in sorted AEC II contrasted to downtrends in irradiated lungs. In conclusion, RILF occurred when GSK-3ß/TGF-ß1 signaling increased ß-catenin levels, which led to the augmentation of AEC II population by elevated lin28/let-7 ratio and the transcription of profibrotic cytokines and factors, thereby inducing AEC II to undergo transdifferentiation into mesenchymal cells.

[Recent progress of robots in stomatology].

With the development of industrial robot technology, robotics has entered the medical field, and the research and development of new robots for many medical applications have become a significant research direction in global robotics. Robots are widely used in various aspects of dentistry, such as prosthodontics, orthodontics, implants, endodontics, and oral surgery. This article mainly introduces the application of robots in stomatology from the above five aspects.

Cross regulation of signaling pathways in gastrointestinal stromal tumor.

The Sonic hedgehog (Shh) signaling pathway may be interrelated with other signaling pathways, such as the phosphoinositide 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways in gastrointestinal stromal tumor (GIST). The present study investigated the interaction among Shh, PI3K and MAPK signaling pathways in GIST cells. The expression of PI3K, MAPK and Shh signaling pathways in GIST-H1 cells were upregulated by endothelial growth factor (EGF) and recombinant Shh (N-shh) stimulation, and were downregulated by specific inhibitors of each signaling pathway. The proliferation rate of GIST-H1 cells were significantly increased under EGF or N-shh treatment (P<0.01). In addition, this effect was partially prevented by the pretreatment of the inhibitors of these signaling pathways. In summary, a cross regulation exists among the Shh, PI3K and MAPK signaling pathways in GIST-H-1 cells. The combined use of the inhibitors of these signaling pathways is a potentially novel option for GIST targeted therapy.

Sarcoidosis in gastric cancer at the time of diagnosis: A case report.

Sarcoidosis is a multisystemic inflammatory disease that commonly affects the lungs and lymphatic system and is characterized by the formation of non-caseating granulomas. Although the association between sarcoidosis and malignant diseases has been well described, it remains controversial whether this association is merely a coincidence or the consequence of a common pathophysiological mechanism. The present study reports a rare case of sarcoidosis that was present in a patient with gastric cancer at the time of diagnosis. A 64-year-old female diagnosed with stage I gastric cancer underwent curative surgery, and the postoperative pathology of the lymph nodes revealed non-caseating granulomas. At the 4-year follow-up, the sarcoidosis remained stable, and no recurrence of cancer was identified. The present case revealed that sarcoidosis and gastric cancer may coexist simultaneously and focused on the potential advantages of histological confirmation in patients with cancer and sarcoidosis.

Tumor sites and microscopic indicators are independent prognosis predictors of gastrointestinal stromal tumors.

Gastrointestinal stromal tumors (GISTs) are the most common among gastrointestinal mesenchymal tumors, but its prognosis has not been accurately predicted by the current risk stratification guidelines, National Institutes of Health classification. In this study, we evaluated the predictive factors for GIST prognosis in a retrospective analysis of 332 patients. The data collected included tumor sites, including the esophagus, stomach, duodenum, small intestine, and extragastrointestinal sites; tumor size; microscopic indicators for malignant tumor behavior, such as the number of dividing cells, cell necrosis, atypical morphology, and invasion into the muscular or mucous layer; and previously established immunohistochemical indicators, CD117, CD34, and discovered on GIST-1 (DOG-1). No single occurrence of any microscopic indicators correlated with the prognosis of GIST; however, the total number of microscopic indicators was a significant prognostic factor of GIST (P < 0.001). Regarding the tumor sites, the order of prognostic risk (from the lowest to the highest) was as follows: the esophagus, stomach, duodenum, small intestine, extragastrointestinal sites, and colorectum. The association between tumor sites and prognosis was significant (P < 0.001). On the other hand, the expression of CD117 or CD34 was not associated with the risk of GIST. Importantly, 91% of the patients (302/332) showed the expression of DOG-1, and the lack of DOG-1 expression was associated with poor prognosis (P < 0.05). In conclusion, both tumor sites and total number of microscopic indicators are independent risk factors associated with the prognosis of GIST. The lack of DOG-1 expression may be predictive of malignant outcome.

ß-catenin is a valuable marker for differential diagnosis of osteoblastoma and osteosarcoma.

Osteoblastoma (OB) and osteosarcoma (OS) are 2 bone tumors that predominantly affect young adults. The clinical management of OS differs significantly from that of OB, and thus, accurate diagnosis of OB and OS is critical in determining appropriate treatment modality. However, in certain cases, OS significantly overlaps with OB in clinical and radiographic characteristics, and therefore, the differential diagnosis of OB and OS can be difficult, especially when biopsy material is insufficient. To date, there have been few reports on markers for differential diagnosis of OB and OS. We have previously shown that the Wnt/ß-catenin pathway is inactivated in OS. In this study, we aimed to investigate whether the cellular distribution pattern of ß-catenin is a potential marker for the differential diagnosis of OB and OS. Immunohistochemical staining was studied in 17 OB samples (21 biopsies; 17 primary and 4 recurrent) and 37 OS samples with complete follow-up information. Moderate-to-strong nuclear ß-catenin staining was found in all OB specimens (17/17). In contrast, positive staining of ß-catenin was found in the cytoplasm and/or membrane but not the nucleus in all 32 cases of nonchondroblastic OS (32/32) and the classic OS component in chondroblastic OS (5/5). The only positive nuclear ß-catenin staining detected in OS biopsies was in chondroblastic OS cells (5/5). In summary, our results indicate that, in addition to conventional histopathologic evaluation, cellular distribution of ß-catenin may be used as a valuable marker in the differential diagnosis of OB and OS. Nuclear ß-catenin staining strongly suggests OB, whereas cytoplasmic/membranous staining of ß-catenin suggests OS.

Angiotensin II type 2 receptor correlates with therapeutic effects of losartan in rats with adjuvant-induced arthritis.

The angiotensin II type 1 receptor (AT1R) blocker losartan ameliorates rheumatoid arthritis (RA) in an experimental model. In RA, AT2R mainly opposes AT1R, but the mechanism by which this occurs still remains obscure. In the present study, we investigated the role of AT2R in the treatment of rats with adjuvant-induced arthritis (AIA) by losartan. Adjuvant-induced arthritis rats were treated with losartan (5, 10 and 15 mg/kg) and methotrexate (MTX; 0.5 mg/kg) in vivo from day 14 to day 28. Arthritis was evaluated by the arthritis index and histological examination. Angiotensin II, tumour necrosis factor-α, and VEGF levels were examined by ELISA. The expression of AT1R and AT2R was detected by western blot and immunohistochemistry analysis. After stimulation with interleukin-1ß in vitro, the effects of the AT2R agonist CGP42112 (10(-8) -10(-5)  M) on the chemotaxis of monocytes induced by 10% foetal calf serum (FCS) were analysed by using Transwell assay. Subsequently, the therapeutic effects of CGP42112 (5, 10 and 20 µg/kg) were evaluated in vivo by intra-articular injection in AIA rats. After treatment with losartan, the down-regulation of AT1R expression and up-regulation of AT2R expression in the spleen and synovium of AIA rats correlated positively with reduction in the polyarthritis index. Treatment with CGP42112 inhibited the chemotaxis of AIA monocytes in vitro, possibly because of the up-regulation of AT2R expression. Intra-articular injection with CGP42112 (10 and 20 µg/kg) ameliorated the arthritis index and histological signs of arthritis. In summary, the present study strongly suggests that the up-regulation of AT2R might be an additional mechanism by which losartan exerts its therapeutic effects in AIA rats.

Comparative efficacy of TACI-Ig with TNF-alpha inhibitor and methotrexate in DBA/1 mice with collagen-induced arthritis.

The efficacies of TACI-Ig, rhTNFR:Fc and Methotrexate were compared in collagen-induced arthritis (CIA) mice. Sixty animals were divided into six groups: TACI-Ig (9 mg/kg), rhTNFR:Fc (4 mg/kg), Methotrexate (2mg/kg) and IgG-Fc (9 mg/kg) groups and were given medication for six weeks. Meanwhile, normal and CIA mice were given as control. The different efficacies of drugs were evaluated by the analyses of ankle joints and spleens pathology, cytokines, T and B lymphocytes subsets. TACI-Ig and rhTNFR:Fc reduced arthritis scores seven days later than that of Methotrexate. TACI-Ig and Methotrexate were superior to rhTNFR:Fc in reduction synovial hyperplasia and cell infiltration scores. The same result was observed for scores of spleens histopathology. TACI-Ig and Methotrexate presented higher efficacy than rhTNFR:Fc on B lymphocyte stimulator, but TACI-Ig was inferior to rhTNFR:Fc on TNF-alpha. TACI-Ig and Methotrexate could reduce significantly IgA and IgM, but rhTNFR:Fc had no effects on these immunoglobulins. TACI-Ig had more efficacy than rhTNFR:Fc in the decrease of CD4(+)CD154(+) T cell. TACI-Ig and Methotrexate also reduced CD4(+)CD69(+) T cell, rhTNFR:Fc had no effects on the T cell subset. TACI-Ig and Methotrexate were superior to rhTNFR:Fc on CD4(+)CD62L(+)T cells. TACI-Ig and Methotrexate could reduce CD19(+)IgD(+) and CD19(+)CD21(+) B cells, but rhTNFR:Fc had no obvious effect on above B cells subsets. TACI-Ig is as effective as rhTNFR:Fc and Methotrexate on CIA mice by ameliorating joint and spleen pathology, regulating T and B lymphocytes function, although different mechanisms among them. This study would be useful for treatment selection of rheumatoid arthritis in different pathological conditions.

Pro-apoptotic effect of epigallo-catechin-3-gallate on B lymphocytes through regulating BAFF/PI3K/Akt/mTOR signaling in rats with collagen-induced arthritis.

To investigate the role of PI3K/Akt/mTOR signaling mediated by B cell-activating factor belonging to the TNF family (BAFF) involved in anti-apoptosis of B lymphocytes in rats with collagen-induced arthritis (CIA) and the regulation of epigallo-catechin-3-gallate (EGCG). Sprague-Dawley rats were immunized to induce CIA. CIA rats were randomly separated into different groups and treated with EGCG (40, 80 mg/kg), Paeoniflorin (100mg/kg) from day 18 to day 38 after immunization. The effects of EGCG on B lymphocytes were evaluated by the levels of BAFF, anti-CII antibody, IgA, IgG and IgM, and the expressions of BAFF receptor, P110δ, p-Akt, mTORC1, Bcl-xL and Bim. B lymphocyte proliferations were analyzed by MTT assay. Apoptosis of B lymphocyte were assayed by flow cytometry. Results showed that, in CIA rats, the levels of BAFF, anti-CII antibody, IgA, IgG and IgM enhanced. BAFF receptor, P110δ, p-AKT, mTORC1 and Bcl-xL were expressed highly, while Bim expression decreased. EGCG (40, 80 mg/kg) and Paeoniflorin decreased the levels of BAFF, anti-CII antibody, IgA, IgG, IgM and the expressions of BAFF receptor, P110δ, p-AKT, mTORC1, Bcl-xL in CIA rats, and increased Bim expression. Further studies showed that EGCG could reduce the expression of P110δ and mTORC1 in vitro. EGCG inhibited B lymphocyte proliferation and induced B lymphocyte apoptosis. In conclusion, BAFF/BAFF receptor might regulate B cell anti-apoptosis through PI3K/Akt/mTOR pathway. EGCG had therapeutic effects on CIA rats, which might be relative to the inhibition effects of EGCG on BAFF and PI3K/Akt/mTOR signaling, and then the apoptosis of B lymphocytes was promoted further.

Hedgehog signaling pathway mediates invasion and metastasis of hepatocellular carcinoma via ERK pathway.

AIM: To investigate the role of Hedgehog (Hh) signaling pathway in the invasion and metastasis of human hepatocellular carcinoma (HCC). METHODS: Eighty six HCC tissues samples and HCC cell line Bel-7402 were examined. The protein expression of sonic hedgehog (Shh), nuclear glioma-associated oncogene-1 (Gli1), MMP-9 and p-ERK1/2 in HCC was analyzed using immunohistochemistry and Western blot analysis. Boyden chamber assay and wound-healing assay were used to quantify the invasion and metastasis of Bel-7402 cells. RESULTS: In 86 HCC tissue samples, the positive ratio of Shh and nucleus Gli1 was 67.44% (58/86) and 60.47% (52/86), respectively; the expression of nucleus Gli1 was correlated with the tumor pathological grade (P=0.034), and with the ability of the tumor to invade and metastasize (P=0.001); the expression of nucleus Gli1 was also correlated with p-ERK1/2 (P=0.031) and with MMP-9 (P=0.034). Neither Shh, nor nucleus Gli1 was observed in normal liver tissue. KAAD-cyclopamine (KAAD-cyc), a specific inhibitor of the Hh pathway, at the concentrations of 1 and 4 µmol/L inhibited the invasion and migration of Bel-7402 cells and decreased the expression of Gli1 in nucleus and MMP-9, p-ERK1/2 proteins in Bel-7402 cells. On the other hand, Shh, a ligand of the Hh pathway, at the concentration of 0.5 µg/mL produced opposite effects. The MAPK pathway inhibitors U0126 and PD98059 at the concentrations of 5 and 10 µmol/L inhibited invasion and metastasis of Bel-7402 cells induced by Shh, and decreased the expression of p-ERK1/2 and MMP-9. However, U0126 and PD98059 had no effect on the expression of Gli1. CONCLUSION: Hh signaling pathway mediates invasion and metastasis of human HCC by up-regulating the protein expression of MMP-9 via ERK pathway.

BAFF/BAFF-R involved in antibodies production of rats with collagen-induced arthritis via PI3K-Akt-mTOR signaling and the regulation of paeoniflorin.

ETHNOPHARMACOLOGICAL RELEVANCE: Paeoniflorin (Pae) is extracted from the root of paeonia lactiflora which have attracted attention for anti-rheumatic and immune modulating properties. AIM OF THE STUDY: To investigate the role of PI3K/Akt/mTOR signaling mediated by BAFF/BAFF-R in antibodies production and the regulation of Pae on the signaling pathway in rats with collagen-induced arthritis (CIA). MATERIALS AND METHODS: CIA rats were randomly separated into different groups and treated with Pae (25, 100mg/kg) from day 18 to day 38 after immunization. The effects of Pae on B lymphocytes of CIA rats were evaluated by the levels of BAFF, anti-CII antibody, IgA, IgG and IgM, and the expressions of BAFF-R, PI3K, p-Akt and mTOR. RESULTS: In CIA rats, the levels of anti-CII antibody, IgA, IgG and IgM in serum enhanced, BAFF, BAFF-R, PI3K, p-Akt and mTOR were highly expressed. Pae (100mg/kg) obviously decreased arthritis score, relieved ankle and paw swelling, improved spleen histopathology in CIA rats, decreased the levels of IgA, IgM, IgG and anti-CII antibody, and significantly decreased the expressions of BAFF, BAFF-R, PI3K, p-Akt and mTOR. CONCLUSION: PI3K/Akt/mTOR signaling mediated by BAFF/BAFF-R participates in antibodies production by B lymphocytes of CIA rats. Pae had therapeutic effects on rats with CIA. These effects might be relative to regulating PI3K/Akt/mTOR signal mediated by BAFF/BAFF-R, and down regulate the antibodies production further.

Therapeutic effects of TACI-Ig on collagen-induced arthritis by regulating T and B lymphocytes function in DBA/1 mice.

To investigate the abnormal function of T and B lymphocytes involved in collagen-induced arthritis in DBA/1 mice and the regulation role of TACI-Ig on T and B lymphocytes, collagen-induced arthritis models were established in DBA/1 mice. Mice were divided randomly into eight groups, including normal, collagen-induced arthritis model, TACI-Ig (0.350, 1.105, 3.333, 10, and 30 mg/kg) and IgG-Fc (10mg/kg) treated groups. The effect of TACI-Ig on collagen-induced arthritis was evaluated by arthritis scores, joints and spleens histopathology, paws radiology, and indices of thymus and spleen. T and B lymphocyte proliferations were assayed by [(3)H]-TdR method. B lymphocyte stimulator and prostaglandin E(2) in serum were assayed by enzyme linked immunosorbent assay. The subsets of T and B lymphocytes were assayed by flow cytometry. Results showed that the onset of paw-swelling was on day 31 after immunization. The peak of inflammation appeared on day 42 and then declined after day 63. Compared with normal mice, collagen-induced arthritis mice have increased arthritis scores, spleen and thymus indices, radiograph scores of joints, and pathology scores of joints and spleens. TACI-Ig could ameliorate these changes and reduce the increased serum level of B lymphocyte stimulator and prostaglandin E(2). Further studies showed that TACI-Ig inhibited T and B lymphocyte proliferation response, and inhibited differentiation and activity of T and B lymphocytes in collagen-induced arthritis mice. In conclusion, TACI-Ig has a good therapeutic action on collagen-induced arthritis mice, which might be related to the regulation of TACI-Ig on inflammation mediators and abnormal function of T and B lymphocytes.