Lycopene alleviates food allergy by modulating the PI3K/AKT pathway in peanut-sensitized BALB/c mice.

Food allergies, which lead to life-threatening acute symptoms, are considered an important public health problem. Therefore, it is essential to develop efficient preventive and treatment measures. We developed a crude peanut protein extract (PPE)-induced allergy mouse model to investigate the effects of lycopene on peanut allergy. Mice were divided into four groups: 5 mg/kg lycopene, 20 mg/kg lycopene, no treatment, and control groups. Serum inflammatory factors were detected using enzyme-linked immunosorbent assay. In addition, pathology and immunohistochemistry analyses were used to examine the small intestine of mice. We found that lycopene decreased PPE-specific immunoglobulin E (IgE) and IL-13 levels in the serum, relieved small intestine inflammation, attenuated the production of histamine and mouse mast cell protease-1, and downregulated PI3K and AKT1 expression in the small intestine tissues of mice allergic to peanuts. Our results suggest that lycopene can ameliorate allergy by attenuating the PI3K/AKT pathway and the anaphylactic reactions mediated by PPE-specific IgE.

Quantitative proteomic dataset of whole protein in three melanoma samples of 92.1, 92.1-A and 92.1-B.

Distant metastasis is common in ocular uveal melanoma (uveal melanoma, UM) [1], with possible identification of relevant protein markers in peripheral blood [2], [3]. Proteomics analyses serve as a basis for the screening of new target proteins. However, it is difficult to determine whether the relevant proteins in peripheral blood are the same kinesins as those in primary lesions and metastases. Specially in this study, human UM cells (92.1) [4] were inoculated into the back of the eyeball and the brain of inbred line nude mice transplanted with enhanced green fluorescent protein (EGFP) [5], respectively, to simulate the growth of UM in situ and in brain metastases. A database was established as follows: Firstly, the xenograft was taken for monoclonal re-culture and amplification. Then, the cells after amplification (92.1-A in the back of the eyeball and 92.1-B in the brain) and their parent cells (92.1) were subjected to Tandem Mass Tag (TMT)-labeling proteomic analysis and liquid chromatography-mass spectrometry (LC-MS). Covering differential proteomes of three cell lines in a pairwise model, the data could be used to further screen the kinesins that play a vital role in regulating the growth of UM.

Proteomics analysis: inhibiting the expression of P62 protein by chloroquine combined with dacarbazine can reduce the malignant progression of uveal melanoma.

BACKGROUND: Although uveal melanoma (UM) at the early stage is controllable to some extent, it inevitably ultimately leads to death due to its metastasis. At present, the difficulty is that there is no way to effectively tackle the metastasis. It is hypothesized that these will be treated by target molecules, but the recognized target molecule has not yet been found. In this study, the target molecule was explored through proteomics. METHODS: Transgenic enhanced green fluorescent protein (EGFP) inbred nude mice, which spontaneously display a tumor microenvironment (TME), were used as model animal carriers. The UM cell line 92.1 was inoculated into the brain ventricle stimulating metastatic growth of UM, and a graft re-cultured Next, the UM cell line 92.1-A was obtained through monoclonal amplification, and a differential proteomics database, between 92.1 and ectopic 92.1-A, was established. Finally, bioinformatics methodologies were adopted to optimize key regulatory proteins, and in vivo and in vitro functional verification and targeted drug screening were performed. RESULTS: Cells and tissues displaying green fluorescence in animal models were determined as TME characteristics provided by hosts. The data of various biological phenotypes detected proved that 92.1-A were more malignant than 92.1. Besides this malignancy, the key protein p62 (SQSTM1), selected from 5267 quantifiable differential proteomics databases, was a multifunctional autophagy linker protein, and its expression could be suppressed by chloroquine and dacarbazine. Inhibition of p62 could reduce the malignancy degree of 92.1-A. CONCLUSIONS: As the carriers of human UM orthotopic and ectopic xenotransplantation, transgenic EGFP inbred nude mice clearly display the characteristics of TME. In addition, the p62 protein optimized by the proteomics is the key protein that increases the malignancy of 92.1 cells, which therefore provides a basis for further exploration of target molecule therapy for refractory metastatic UM.

Computational Studies of Coinage Metal Anion M- + CH3X (X = F, Cl, Br, I) Reactions in Gas Phase.

We characterized the stationary points along the nucleophilic substitution (SN2), oxidative insertion (OI), halogen abstraction (XA), and proton transfer (PT) product channels of M- + CH3X (M = Cu, Ag, Au; X = F, Cl, Br, I) reactions using the CCSD(T)/aug-cc-pVTZ level of theory. In general, the reaction energies follow the order of PT > XA > SN2 > OI. The OI channel that results in oxidative insertion complex [CH3-M-X]- is most exothermic, and can be formed through a front-side attack of M on the C-X bond via a high transition state OxTS or through a SN2-mediated halogen rearrangement path via a much lower transition state invTS. The order of OxTS > invTS is inverted when changing M- to Pd, a d10 metal, because the symmetry of their HOMO orbital is different. The back-side attack SN2 pathway proceeds via typical Walden-inversion transition state that connects to pre- and post-reaction complexes. For X = Cl/Br/I, the invSN2-TS's are, in general, submerged. The shape of this M- + CH3X SN2 PES is flatter as compared to that of a main-group base like F- + CH3X, whose PES has a double-well shape. When X = Br/I, a linear halogen-bonded complex [CH3-X∙··M]- can be formed as an intermediate upon the front-side attachment of M on the halogen atom X, and it either dissociates to CH3 + MX- through halogen abstraction or bends the C-X-M angle to continue the back-side SN2 path. Natural bond orbital analysis shows a polar covalent M-X bond is formed within oxidative insertion complex [CH3-M-X]-, whereas a noncovalent M-X halogen-bond interaction exists for the [CH3-X∙··M]- complex. This work explores competing channels of the M- + CH3X reaction in the gas phase and the potential energy surface is useful in understanding the dynamic behavior of the title and analogous reactions.

Adjuvant chemotherapy indications for stage I gastric cancer patients with negative lymph node.

PURPOSE: Whether adjuvant chemotherapy (AC) has a survival benefit for pathological stage Ⅰ (T1N0 and T2N0) gastric cancer (GC) patients with negative lymph node (N0) remains controversial. METHODS: Patients with surgically resected, histologically confirmed pT1N0 and pT2N0 GC between January 2011 and December 2017 at the National Cancer Center, China, were retrospectively reviewed. RESULTS: A total of 1601 patients who met the inclusion criteria were identified. Independent risk factors for reduced overall survival (OS) identified in the Cox regression analysis were male sex (hazard ratio [HR] 1.454, 95% confidence interval [CI] 1.127-1.876), age ≥ 65 years (HR 1.367; 95% CI 1.071-1.744 ), T2 stage (HR 1.283; 95% CI 1.005-1.638), tumor size > 3 cm (HR 1.704; 95% CI 1.346-2.158), examined lymph nodes (EN) ≤ 15 (HR 1.327; 95% CI 1.058-1.664), and non-signet ring cell carcinoma (Non-SRCC) (HR 1.639; 95% CI 1.123-2.392). While only T2 stage (HR 1.410; 95% CI 1.026-1.936), tumor size > 3 cm (HR 1.755; 95% CI 1.285-2.397), examined lymph nodes (EN) ≤ 15 (HR 1.489; 95% CI 1.101-2.015) were independent risk factors for cause-specific survival (CSS). We divided patients with pT2N0 into four sub-categories according to two significant prognostic factors (size and EN) and found that only patient in group 3 (EN ≤ 15, size >3 cm) with improved CSS benefit from AC (p = 0.049). More significant CSS benefit from AC was identified in Non-SRCC patients within group 3 (p = 0.034). CONCLUSION: An additional survival benefit related to AC is expected for selected pT2N0 patients. Non-SRCC patients with EN ≤ 15 and tumor size >3 cm may be particularly appropriate candidates for AC.

The HIF-1α/p53/miRNA-34a/Klotho axis in retinal pigment epithelial cells promotes subretinal fibrosis and exacerbates choroidal neovascularization.

Wet age-related macular degeneration (wAMD), characterized by choroidal neovascularization (CNV), is a leading cause of irreversible vision loss among elderly people in developed nations. Subretinal fibrosis, mediated by epithelial-mesenchymal transition (EMT) of retinal pigment epithelium (RPE) cells, leads to unsuccessful anti-vascular endothelial growth factor (VEGF) agent treatments in CNV patients. Under hypoxic conditions, hypoxia-inducible factor-1α (HIF-1α) increases the stability and activation of p53, which activates microRNA-34a (miRNA-34a) transcription to promote fibrosis. Additionally, Klotho is a target gene of miRNA-34a that inhibits fibrosis. This study aimed to explore the role of the HIF-1α/p53/miRNA-34a/Klotho axis in subretinal fibrosis and CNV. Hypoxia-induced HIF-1α promoted p53 stability, phosphorylation and nuclear translocation in ARPE-19 cells (a human RPE cell line). HIF-1α-dependent p53 activation up-regulated miRNA-34a expression in ARPE-19 cells following hypoxia. Moreover, hypoxia-induced p53-dependent miRNA-34a inhibited the expression of Klotho in ARPE-19 cells. Additionally, the HIF-1α/p53/miRNA-34a/Klotho axis facilitated hypoxia-induced EMT in ARPE-19 cells. In vivo, blockade of the HIF-1α/p53/miRNA-34a/Klotho axis alleviated the formation of mouse laser-induced CNV and subretinal fibrosis. In short, the HIF-1α/p53/miRNA-34a/Klotho axis in RPE cells promoted subretinal fibrosis, thus aggravating the formation of CNV.

Indications for adjuvant chemotherapy in patients with pT1N1M0 gastric cancer: a single-center experience.

PURPOSE: Whether adjuvant chemotherapy (AC) has a survival benefit for all patients with pathological stage pT1N1M0 (Stage IB) gastric cancer (GC) remains controversial. METHODS: All patients with surgically resected, histologically confirmed pT1N1M0 GC between January 2011 and December 2017 at the National Cancer Center, China, were retrospectively reviewed. RESULTS: A total of 179 patients with pT1N1M0 were identified. Survival analysis showed that both overall survival (OS) and cause-specific survival (CSS) were significantly different between patients treated with and without AC (p < 0.01). Independent risk factors for reduced OS identified in the Cox regression analysis in patients with pT1N1M0 cancer were sex (male sex, hazard ratio [HR] 2.470, 95% confidence interval [CI] 1.294-4.718), examined lymph nodes (EN) (EN ≤ 15, HR 2.402; 95% CI 1.329-4.341), and AC (treated without AC, HR 2.554; 95% CI 1.393-4.681), which were also independent risk factors for reduced CSS. We divided patients with pT1N1M0 into three risk categories (high, moderate, and low) according to two significant prognostic factors (sex and EN) and found that both OS and CSS were significantly different between the three risk groups (p < 0.05). CONCLUSION: An additional survival benefit related to AC is expected for selected pT1N1M0 patients. Male patients with EN ≤ 15 may be particularly appropriate candidates for AC.

Artificial intelligence in gastric cancer: a systematic review.

OBJECTIVE: This study aims to systematically review the application of artificial intelligence (AI) techniques in gastric cancer and to discuss the potential limitations and future directions of AI in gastric cancer. METHODS: A systematic review was performed that follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Pubmed, EMBASE, the Web of Science, and the Cochrane Library were used to search for gastric cancer publications with an emphasis on AI that were published up to June 2020. The terms "artificial intelligence" and "gastric cancer" were used to search for the publications. RESULTS: A total of 64 articles were included in this review. In gastric cancer, AI is mainly used for molecular bio-information analysis, endoscopic detection for Helicobacter pylori infection, chronic atrophic gastritis, early gastric cancer, invasion depth, and pathology recognition. AI may also be used to establish predictive models for evaluating lymph node metastasis, response to drug treatments, and prognosis. In addition, AI can be used for surgical training, skill assessment, and surgery guidance. CONCLUSIONS: In the foreseeable future, AI applications can play an important role in gastric cancer management in the era of precision medicine.

Novel enhanced GFP-positive congenic inbred strain establishment and application of tumor-bearing nude mouse model.

Transgenic GFP gene mice are widely used. Given the unique advantages of immunodeficient animals in the field of oncology research, we aim to establish a nude mouse inbred strain that stably expresses enhanced GFP (EGFP) for use in transplanted tumor microenvironment (TME) research. Female C57BL/6-Tg(CAG-EGFP) mice were backcrossed with male BALB/c nude mice for 11 generations. The genotype and phenotype of novel inbred strain Foxn1nu .B6-Tg(CAG-EGFP) were identified by biochemical loci detection, skin transplantation and flow cytometry. PCR and fluorescence spectrophotometry were performed to evaluate the relative expression of EGFP in different parts of the brain. Red fluorescence protein (RFP) gene was stably transfected into human glioma stem cells (GSC), SU3, which were then transplanted intracerebrally or ectopically into Foxn1nu .B6-Tg(CAG-EGFP) mice. Cell co-expression of EGFP and RFP in transplanted tissues was further analyzed with the Live Cell Imaging System (Cell'R, Olympus) and FISH. The inbred strain Foxn1nu .B6-Tg(CAG-EGFP) shows different levels of EGFP expression in brain tissue. The hematological and immune cells of the inbred strain mice were close to those of nude mice. EGFP was stably expressed in multiple sites of Foxn1nu .B6-Tg(CAG-EGFP) mice, including brain tissue. With the dual-fluorescence tracing transplanted tumor model, we found that SU3 induced host cell malignant transformation in TME, and tumor/host cell fusion. In conclusion, EGFP is differentially and widely expressed in brain tissue of Foxn1nu .B6-Tg(CAG-EGFP), which is an ideal model for TME investigation. With Foxn1nu .B6-Tg(CAG-EGFP) mice, our research demonstrated that host cell malignant transformation and tumor/host cell fusion play an important role in tumor progression.

Surgical management of oligometastatic disease in gastric cancer.

A distinctive subset of metastatic gastric cancer (MGC) is oligometastatic disease (OMD), which is characterized by metastatic lesions limited in number and location. Although growing evidence mainly based on retrospective analysis or single center case series has shown favorable prognosis in the management of OMD in gastric cancer with aggressive local treatment, no existing guidelines explicitely address the definition of OMD and there are still controversial opinions on how to proceed in a new era with more effective systemic therapy selection. In this review, we present the current advances and evidence as well as controversial on the management of OMD in MGC, including the definition, diagnosis, local aggressive treatments especially surgery, prognostic factors, current ongoing randomized clinical studied as well as challenges facing the field.

MLN4924 inhibits hedgehog signaling pathway and activates autophagy to alleviate mouse laser-induced choroidal neovascularization lesion.

Neovascular age-related macular degeneration (nAMD), featured as choroidal neovascularization (CNV), can cause blindness in the elderly population. MLN4924, a highly selective small-molecule inhibitor of NEDD8 (neuronal precursor cell-expressed developmentally down-regulated protein 8)-activating enzyme (NAE), inhibits the proliferation, angiogenesis and inflammation of multiple cancers via up-regulating hedgehog pathway-regulated autophagy. MLN4924 intraperitoneal injection mitigated the leakage, area and volume of mouse laser-induced CNV lesion. Additionally, compared to CNV 7 d group, MLN4924 treated mouse retina-retinal pigment epithelium (RPE)-choroid complex showed decreased expression of hedgehog pathway-associated molecules patched 1 (PTCH1), smoothened (SMO), GLI family zinc finger 1 (GLI1) and GLI family zinc finger 2 (GLI2) with increased expression of autophagy-associated molecules sequestosome 1 (p62) and LC microtubule-associated protein 1 light chain 3 (LC3). Meanwhile, human choroidal endothelial cells (HCECs) exposed to hypoxia condition also showed decreased expression of hedgehog pathway-associated molecules and increased expression of autophagy-associated molecules. Compared to hypoxia + MLN4924 group, SMO agonist SAG up-regulated hedgehog pathway and down-regulated autophagy, whereas autophagy inhibitor PIK-III inhibited autophagy with no effect on hedgehog pathway, indicating that MLN4924 facilitated autophagy of HCECs via hindering hedgehog pathway under hypoxia condition. Finally, MLN4924 inhibited proliferation, migration and tube formation of HCECs via boosting hedgehog pathway-regulated autophagy. In summary, MLN4924 relieved the formation of mouse laser-induced CNV lesion might via up-regulating hedgehog pathway-regulated autophagy. The results provide a potential interfering strategy for nAMD targeting the autophagy of choroidal endothelial cells.

Overexpression of GBP1 predicts poor prognosis and promotes tumor growth in human glioblastoma multiforme.

OBJECTIVE: Guanylate binding protein-1 (GBP1) is highly associated with cell proliferation, and can modulate growth and invasiveness of gliomas. The relationship between GBP1 expression and the prognosis of glioma patients is further evaluated for the purpose of investigating whether GBP1 can serve as an predictor for evaluating prognosis of glioma patients. METHODS: GBP1 expression in 528 glioblastoma multiforme (GBM) patients of The Cancer Genome Atlas (TCGA) database were investigated, then 103 surgical specimens from glioma patients in our center were further evaluated. The effect of GBP1 on proliferation, invasion and migration of glioma cells in vitro was analyzed, and the effects of GBP1 on sensitivity of radiotherapy and chemotherapy on glioma cells in vitro were also analyzed. GBP1 associated signaling pathways were identified with Gene Set Enrichment Analysis (GSEA). Besides, the effect of GBP1 expression on proliferation of glioma cells in vivo was analyzed. RESULTS: In both TCGA database and our clinical data, GBM tissues exhibited increased mRNA expression of GBP1 gene, its expression level was co-related to PETN deletion and EGFR amplification, and was associated with prognosis of GBM patients. GBP1 overexpression can enhance migration and invasion ability of tumor cells in vitro, and in vivo studies showed that GBP1 can promote tumor proliferation, decrease survival in tumor-bearing mice. GSEA analysis predicted that GBP1 may play its biological roles via toll-like receptor pathway. CONCLUSION: This study provides new insights and evidences that high level expression of GBP1 is significantly correlated with progression and prognosis in GBMs. Furthermore, transfection of GBP1 revealed its regulation on migration and invasiveness of glioma cells, decreasing sensitivity of chemotherapeutic agent, shortening survival of tumor-bearing animals. These data demonstrate that GBP1 may serve as a novel prognostic biomarker and a potential therapeutic target for gliomas.

Prognostic value of NUSAP1 in progression and expansion of glioblastoma multiforme.

Nucleolar and spindle-associated protein (NUSAP1) is a microtubule and chromatin-binding protein that stabilizes microtubules to prevent depolymerization, maintains spindle integrity. NUSAP1 could cross-link spindles into aster-like structures, networks and fibers. It has also been found to play roles in progression of several cancers. However, the potential correlation between NUSAP1 and clinical outcome in patients with glioblastoma multiforme (GBM) remains largely unknown. In the current study, we demonstrated that NUSAP1 was significantly up-regulated in GBM tissues compared with adult non-tumor brain tissues both in a validated cohort and a TCGA cohort. In addition, Kaplan-Meier analysis indicated that patients with high NUSAP1 expression had significantly lower OS (P = 0.0027). Additionally, in the TCGA cohort, NUSAP1 expression was relatively lower in GBM patients within the neural and mesenchymal subtypes compared to other subtypes, and associated with the status of several genetic aberrations such as PTEN deletion and wild type IDH1. The present study provides new insights and evidence that NUSAP1 over-expression was significantly correlated with progression and prognosis of GBM. Furthermore, knockdown of NUSAP1 revealed its regulation on G2/M progression and cell proliferation (both in vitro and in vivo). These data demonstrate that NUSAP1 could serve as a novel prognostic biomarker and a potential therapeutic target for GBM.

Research on human glioma stem cells in China.

Research on human glioma stem cells began early in the 21st century and since then has become a rapidly growing research field with the number of publications increasing year by year. The research conducted by our diverse group of investigators focused primarily on cell culture techniques, molecular regulation, signaling pathways, cancer treatment, the stem cell microenvironment and the cellular origin and function of glioma stem cells. In particular, we put forward our view that there are inverse or forward transformations among neural stem cells, glial cells and glioma stem cells in glioma tissues under certain conditions. Based on the background of the progress of international research on human glioma stem cells, we aim to share our progress and current findings of human glioma stem cell research in China with colleagues around the world.

Human glioma stem-like cells induce malignant transformation of bone marrow mesenchymal stem cells by activating TERT expression.

We investigated whether glioma stem-like cells (GSCs) malignantly transformed bone marrow mesenchymal stem cells (tBMSCs) in the tumor microenvironment. Transplantation of enhanced green fluorescence protein (EGFP)-labeled BMSCs into irradiated athymic nude mice was followed by intracranial injection of red fluorescent protein-expressing glioma stem-like cells (SU3-RFP-GSCs). Singly cloned EGFP-BMSCs, harvested from the intracranial tumors showed TERT overexpression, high proliferation, colony formation and invasiveness in Transwell matrigel assays. Transfection of normal BMSCs with TERT (TERT-BMSCs) enhanced proliferation, colony formation and invasiveness, though these characteristics remained lower than in tBMSCs. The tBMSCs and TERT-BMSCs showed high surface expression of CD44, CD105, CD29 and CD90 and an absence of CD31, CD34, CD45, and CD11b, as in normal BMSCs. Alizarin red S and oil red O staining confirmed tBMSCs and TERT-BMSCs transdifferentiated into osteocytes and adipocytes, respectively. When normal BMSCs were indirectly co-cultured in medium from SU3-RFP-GSCs, they exhibited increased growth and proliferation, suggesting paracrine factors from GSCs induced their malignant transformation. Tumorigenicity assays in athymic nude mice showed that transplanted tBMSCs and TERT-BMSCs generated 100% and 20% subcutaneous tumors, respectively, while normal BMSCs generated no tumors. GSCs thus induce malignant transformation of BMSCs by activating TERT expression in BMSCs.

Midline Suboccipital Endoscopic Transcerebellomedullary Fissure Keyhole Approach.

OBJECTIVE: To study the endoscopic anatomy of the 4th ventricle and lateral brainstem regions via the midline suboccipital endoscopic transcerebellomedullary fissure keyhole approach assisted by a neuronavigation system and discuss the feasibility and indications of this approach. MATERIALS AND METHODS: Craniotomy procedures performed via the midline suboccipital endoscopic transcerebellomedullary fissure keyhole approach were simulated on 8 adult cadaveric heads fixed by formalin, and the related anatomic structures in the 4th ventricles or around the brainstem were observed through the 0° endoscope or alternatively 30° one. A neuronavigation system was used to measure the exposed area of the floor of 4th ventricle, the maximum exposure range, the length of the floor of 4th ventricle, the shortest distance from the midpoint of posterior arch of atlas to the opening of the aqueduct in the 4th ventricle and to the jugular foramen on both sides, respectively. RESULTS: All the anatomic structures within the 4th ventricle and partial anatomic landmarks around brainstem were identified by means of the midline suboccipital endoscopic transcerebellomedullary fissure keyhole approach. The exposed area of the floor of 4th ventricle is 459.68 ±â€Š73.71 mm. However, the total exposed area is 1601.70 ±â€Š200.76 mm. The length of the floor of 4th ventricle is 36.08 ±â€Š2.63 mm. The shortest distance from the midpoint of posterior arch of atlas to the opening of the aqueduct in the 4th ventricle is 63.87 ±â€Š2.97 mm, to the jugular foramen on both sides, respectively, is 40.11 ±â€Š2.47 mm/40.30 ±â€Š2.31 mm. CONCLUSIONS: Midline suboccipital endoscopic transcerebellomedullary fissure keyhole approach can basically meet the medial and lateral route of the transcerebellomedullary fissure approach. A tumor within the 4th ventricle or near the jugular tubercle extending into the 4th ventricle through the cerebellomedullary fissure can be removed by this approach.

The novel cyclophilin D inhibitor compound 19 protects retinal pigment epithelium cells and retinal ganglion cells from UV radiation.

Excessive Ultra violet (UV) radiation induces injuries to retinal pigment epithelium (RPE) cells (RPEs) and retinal ganglion cells (RGCs), causing retinal degeneration. Cyclophilin D (Cyp-D)-dependent mitochondrial permeability transition pore (mPTP) opening mediates UV-induced cell death. In this study, we show that a novel Cyp-D inhibitor compound 19 efficiently protected RPEs and RGCs from UV radiation. Compound 19-mediated cytoprotection requires Cyp-D, as it failed to further protect RPEs/RGCs from UV when Cyp-D was silenced by targeted shRNAs. Compound 19 almost blocked UV-induced p53-Cyp-D mitochondrial association, mPTP opening and subsequent cytochrome C release. Further studies showed that compound 19 inhibited UV-induced reactive oxygen species (ROS) production, lipid peroxidation and DNA damage. Together, compound 19 protects RPEs and RGCs from UV radiation, possibly via silencing Cyp-D-regulated intrinsic mitochondrial death pathway. Compound 19 could a lead compound for treating UV-associated retinal degeneration diseases.

Lipasin, a biomarker of diabetic retinopathy.

The present study recruited 74 participants with type 2 diabetes, among which 23 had retinopathy. Those with retinopathy had a longer duration of diabetes and higher levels of lipasin compared with those without retinopathy. Logistic regression revealed that lipasin was independently and significantly associated with retinopathy even after adjustments for confounders.

Association of serum and vitreous concentrations of osteoprotegerin with diabetic retinopathy.

BACKGROUND: Angiogenesis is involved in the pathogenesis of diabetic retinopathy. Osteoprotegerin, a recently identified glycoprotein belonging to the tumour necrosis factor receptor superfamily, has been implicated to be correlated with angiogenesis. This study aims to determine whether serum and vitreous concentrations of osteoprotegerin are associated with diabetic retinopathy. METHODS: This study consisted of 254 diabetic patients (100 without diabetic retinopathy, 64 with non-proliferative diabetic retinopathy and 90 with proliferative diabetic retinopathy) and 62 control subjects. Serum and vitreous concentrations of osteoprotegerin were evaluated using enzyme-linked immunosorbent assay method. RESULTS: Serum and vitreous osteoprotegerin concentrations in proliferative diabetic retinopathy patients were significantly elevated compared with those of the other three groups. Non-proliferative diabetic retinopathy patients showed elevated concentrations of serum and vitreous osteoprotegerin compared with patients without diabetic retinopathy. In addition, control subjects had significantly lower serum and vitreous osteoprotegerin concentrations compared with diabetic patients without retinopathy, non-proliferative diabetic retinopathy patients and proliferative diabetic retinopathy patients. CONCLUSIONS: Serum and vitreous osteoprotegerin concentrations are associated with the presence and severity of diabetic retinopathy.

Resection or cryosurgery relates with pancreatic tumor type: primary pancreatic cancer with previous non-pancreatic cancer or secondary metastatic cancer within the pancreas.

OBJECTIVES: We investigated the incidence of primary pancreatic cancer with previous non-pancreatic cancer (PPC) and secondary metastatic cancer within the pancreas (SMC) to elucidate the differential diagnosis and treatment of these lesions. METHODS: The clinical data of 2539 patients with pancreatic mass in Tianjin Cancer Hospital from January 2000 to December 2012 were retrospectively analyzed. All of the 66 patients who showed double or multiple primary cancers or metastatic pancreatic malignancies were included into the PPC group or SMC group, respectively. In addition, PPC patients were compared with 570 patients suffering from pancreatic cancer (PC) alone. RESULTS: For the PPC group (n = 34), the most common previous non-pancreatic cancers were gastric cancer, breast cancer, and thyroid cancer. For the SMC group (n = 32), the most common metastatic tumors were lung cancer, renal cell carcinoma (RCC), and gastric cancer. Multivariate analysis identified age (OR = 1.099; 95% CI, 1.007-1.199), previous tumor type (OR = 1.164; 95% CI, 1.046-1.296), and time interval between two tumors (OR = 1.021; 95% CI, 1.003-1.039) as significant indicators. Significantly better survival times were observed after resection than after cryosurgery in the PPC group (p < 0.001) but not in the SMC group (p = 0.670). CONCLUSIONS: Overall, primary pancreatic cancers are as common as metastasis to the pancreas in patients with a previous cancer. A longer time interval between two tumors indicates a higher possibility that a new pancreatic cancer will occur. Some cancers (particularly RCC) are more likely to metastasize to the pancreas than other cancers. For metastatic cancers, cryosurgery is as effective as resection as a treatment option.