sAPPα Peptide Promotes Damaged Microglia to Clear Alzheimer's Amyloid-ß via Restoring Mitochondrial Function.

Alzheimer's disease (AD) is an age-related neurodegenerative disease with amyloid-ß (Aß) deposition as the main pathological feature. It's an important challenge to find new ways to clear Aß from the brain. The soluble amyloid precursor protein α (sAPPα) is a neuroprotective protein and can attenuate neuronal damage, including toxic Aß. However, the regulatory role of sAPPα in non-neuronal cells, such as microglia, is less reported and controversial. Here, we showed that sAPPα promoted the phagocytosis and degradation of Aß in both normal and damaged microglia. Moreover, the function of damaged microglia was improved by the sAPPα through normalizing mitochondrial function. Furthermore, the results of molecular docking simulation showed that sAPPα had a good affinity with Aß. We preliminarily reveal that sAPPα is similar to antibodies and can participate in the regulation of microglia phagocytosis and degradation of Aß after binding to Aß. sAPPα is expected to be a mild and safe peptide drug or drug carrier for AD.

Oligonucleotide Fluorescence In Situ Hybridization: An Efficient Chromosome Painting Method in Plants.

Fluorescence in situ hybridization (FISH) is an indispensable technique for studying chromosomes in plants. However, traditional FISH methods, such as BAC, rDNA, tandem repeats, and distributed repetitive sequence probe-based FISH, have certain limitations, including difficulties in probe synthesis, low sensitivity, cross-hybridization, and limited resolution. In contrast, oligo-based FISH represents a more efficient method for chromosomal studies in plants. Oligo probes are computationally designed and synthesized for any plant species with a sequenced genome and are suitable for single and repetitive DNA sequences, entire chromosomes, or chromosomal segments. Furthermore, oligo probes used in the FISH experiment provide high specificity, resolution, and multiplexing. Moreover, oligo probes made from one species are applicable for studying other genetically and taxonomically related species whose genome has not been sequenced yet, facilitating molecular cytogenetic studies of non-model plants. However, there are some limitations of oligo probes that should be considered, such as requiring prior knowledge of the probe design process and FISH signal issues with shorter probes of background noises during oligo-FISH experiments. This review comprehensively discusses de novo oligo probe synthesis with more focus on single-copy DNA sequences, preparation, improvement, and factors that affect oligo-FISH efficiency. Furthermore, this review highlights recent applications of oligo-FISH in a wide range of plant chromosomal studies.

Molecular cytogenetic map visualizes the heterozygotic genome and identifies translocation chromosomes in Citrus sinensis.

Citrus sinensis is the most cultivated and economically valuable Citrus species in the world, whose genome has been assembled by three generation sequencings. However, chromosome recognition remains a problem due to the small size of chromosomes, and difficulty in differentiating between pseudo and real chromosomes because of a highly heterozygous genome. Here, we employ fluorescence in situ hybridization (FISH) with 9 chromosome painting probes, 30 oligo pools, and 8 repetitive sequences to visualize 18 chromosomes. Then, we develop an approach to identify each chromosome in one cell through single experiment of oligo-FISH and Chromoycin A3 (CMA) staining. By this approach, we construct a high-resolution molecular cytogenetic map containing the physical positions of CMA banding and 38 sequences of FISH including centromere regions, which enables us to visualize significant differences between homologous chromosomes. Based on the map, we locate several highly repetitive sequences on chromosomes and estimate sizes and copy numbers of each site. In particular, we discover the translocation regions of chromosomes 4 and 9 in C. sinensis "Valencia." The high-resolution molecular cytogenetic map will help improve understanding of sweet orange genome assembly and also provide a fundamental reference for investigating chromosome evolution and chromosome engineering for genetic improvement in Citrus.

Rare massive hepatic hemangioblastoma: A case report.

BACKGROUND: Hepatic hemangioblastoma is an extremely rare disease; only three cases have been reported in the literature, and its magnetic resonance imaging (MRI) findings are unreported. CASE SUMMARY: We report a case of incidental hepatic hemangioblastoma. The patient had no history of von Hippel-Lindau disease or associated clinical signs. Computed tomography and MRI showed a large tumor occupying almost half of the right side of the liver with expansive growth, well-defined borders, heterogeneous mildly progressive enhancement, and visibly enlarged blood supply vessels. Flow voids were observed on T2-weighted imaging. Both diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) map findings of the mass were predominantly inhomogeneous. Postoperative pathology indicated a diagnosis of hemangioblastoma. CONCLUSION: Enlarged peripheral blood-supplying vessels and progressive enhancement seem to be typical imaging features of hepatic hemangioblastoma. However, a solid significantly enhanced mass with a low signal on DWI and a high signal on ADC may also be helpful for the diagnosis of hepatic hemangioblastoma.

cDNA microarray analysis of gene expression profiles in human fibroblast cells irradiated with red light.

In this paper, the cDNA microarray technique was used to investigate the gene expression profiles of human fibroblasts irradiated by low-intensity red light. Proliferation assays showed that the fibroblast HS27 cells responded with a curve effect to different doses of low-intensity red light irradiation at a wavelength of 628 nm. An optimal dose of 0.88 J per cm2 was chosen for subsequent cDNA microarray experiments. The gene expression profiles revealed that 111 genes were regulated by the red light irradiation and can be grouped into 10 functional categories. Most of these genes directly or indirectly play roles in the enhancement of cell proliferation and the suppression of apoptosis. Two signaling pathways, the p38 mitogen-activated protein kinase signaling pathway and the platelet-derived growth factor signaling pathway, were found to be involved in cell growth induced by irradiation of low-intensity red light. Several genes related to antioxidation and mitochondria energy metabolism were also found to express differentially upon irradiation. This study provides insight into the molecular mechanisms associated with the beneficial effects of red light irradiation in accelerating wound healing.

Decreased expression of SOX7 is correlated with poor prognosis in lung adenocarcinoma patients.

Lung adenocarcinoma is the most frequently histologic subtype and the most histologically heterogeneous form of lung cancer. De-regulation of Wnt/ß-catenin signaling pathway is implicated in lung carcinogenesis. SOX7, as a member of high mobility group (HMG) transcription factor family, plays a role in the modulation of the Wnt/ß-catenin signaling pathway. However, the expression pattern and clinicopathological significance of SOX7 in patients with lung adenocarcinoma is still unclear. To address this problem, the SOX7 mRNA expression was detected by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). Immunohistochemical studies were performed on 288 pairs of adjacent normal lung and lung adenocarcinoma tissues with complete follow-up records. Association of SOX7 protein expression with clinical outcomes was evaluated using the Kaplan-Meier method and a multivariate Cox proportional hazards regression model. SOX7 mRNA expression was significantly down-regulated in lung adenocarcinoma compared with matched adjacent normal tissues (P < 0.001). SOX7 protein was expressed in the cytoplasm of lung adenocarcinoma cells in 106/288 (36.8 %) of cases, whereas its immunoreactivities were predominantly located in the cytoplasm of the adjacent normal tissues. The reduced SOX7 expression was correlated with poor differentiation (P = 0.002), lymph node metastasis (P = 0.011) and advanced TNM stage (P = 0.006). Regarding patient survival, the overall survival and the disease-free survival rates were both significantly lower in patients with SOX7-negative tumors than in those with SOX7-positive tumors (P = 0.018 and 0.013, respectively). Multivariate analysis using a Cox proportional-hazards model demonstrated that SOX7 expression status was an independent prognostic factor predicting the overall survival and the disease-free survival of patients with lung adenocarcinoma (P = 0.021 and 0.016, respectively).Our data suggest that the decreased expression of SOX7 is an important feature of lung adenocarcinoma. The expression level of SOX protein may be a useful prognostic marker for patients with lung adenocarcinoma.

Expression of N-myc downstream-regulated gene 1 in primary gallbladder carcinoma and its correlation with clinicopathological features and clinical outcome.

N-myc downstream-regulated gene 1 (NDRG1), a member of the N-myc downstream-regulated gene family, is induced under a wide variety of stress and cell growth-regulatory conditions. In several cancers, recent studies have shown its association with inhibition of tumor metastasis and suggested it to be a tumor suppressor gene. However, its significance in primary gallbladder carcinoma (PGC) has not been studied. Therefore, the aim of this study was to investigate NDRG1 expression in PGC and its prognostic significance. We examined NDRG1 expression in tumor specimens from 138 patients with PGC by immunohistochemistry and analyzed the correlation between NDRG1 expression and clinicopathologic factors or survival. NDRG1 was expressed in 63.8% of PGC but not in the normal epithelium of the gallbladder, remarkably at the invasive front of the tumors. In addition, NDRG1 expression was significantly associated with high histologic grade, advanced pathologic T stage and clinical stage, positive nodal metastasis and venous/lymphatic invasion. Moreover, Kaplan-Meier curves showed that NDRG1 over-expression was significantly related to poor overall and disease-free survival (both P = 0.02). Furthermore, multivariate analyses showed that NDRG1 expression (hazard ratio, 3.338; P = 0.02) and clinical stage (hazard ratio, 3.128; P = 0.03) were independent risk factors for disease-free survival. Our data demonstrate for the first time that NDRG1 expression in PGC was significantly correlated with unfavorable clinicopathologic features and an independent poor prognostic factor for disease-free survival in patients. Taken together, our findings suggest that NDRG1 expression could be used as a novel prognostic factor for patient survival and might be a potential therapeutic target in PGC.

Upregulation of a disintegrin and metalloprotease 8 influences tumor metastasis and prognosis in patients with osteosarcoma.

To investigate the clinicopathological and prognostic value of a disintegrin and metalloprotease 8 (ADAM8) in osteosarcoma. ADAM8 expression in osteosarcoma tissues was examined by immunohistochemistry in 69 patients. ADAM8 was positively expressed in 61 of 69 (88.4%) osteosarcoma specimens with cytoplasmic staining, and also increased in the specimens with recurrence (P = 0.008) and metastasis (P = 0.002). Patients with strong ADAM8 expression had significantly poorer overall survival (OS) and disease-free survival (DFS) (both P < 0.001) when compared with the patients with the weak expression of ADAM8. On multivariate analysis, ADAM8 expression was found to be an independent prognostic factor for both OS (P < 0.001) and DFS (P < 0.001). Our results suggest for the first time that ADAM8 might be applied as a novel marker for the prediction of recurrence and metastasis potency and a significant indicator of poor prognosis for patients with osteosarcoma.

NDRG2 down-regulation and CD24 up-regulation promote tumor aggravation and poor survival in patients with gallbladder carcinoma.

Recent studies have demonstrated that N-Myc downstream-regulated gene 2 (NDRG2) may reduce the metastatic potential of breast cancer and hepatocellular carcinoma cells by regulating the expression of CD24, which is expressed in a large variety of solid tumors. The aim of this study was to clarify the clinical value of NDRG2 and CD24 expression in primary gallbladder carcinoma (GBC). One hundred and thirty GBC tissues were evaluated by immunohistochemistry for NDRG2 and CD24 expression. The associations of NDRG2 and CD24 expression with the clinicopathological characteristics and the overall survival of patients with GBC were analyzed. NDRG2 and CD24 were positively expressed in 49/130 (37.69%) and 107/130 (82.31%) of GBC tissues, respectively. In addition, the tumors with the down-regulation of NDRG2 and the up-regulation of CD24 more frequently had lymph node metastasis and lymphovascular invasion. Moreover, the tumors with the down-regulation of NDRG2 and the up-regulation of CD24 tended to show deeper invasion depth and higher TNM stage. There was a negative correlation between NDRG2 expression and CD24 expression in GBC tissues (r = -0.86, P < 0.001). The patients with NDRG2 negative expression correlated with poor prognosis of GBC (P = 0.01), as opposed to CD24 (P = 0.01). The survival rate of the patients with NDRG2-/CD24+ expression was the lowest (P < 0.001), and conjoined expression of NDRG2-/CD24+ was an independent prognostic indicator of GBC (P = 0.003). Our data suggest that NDRG2 down-regulation or CD24 up-regulation is an important feature of GBC. A combined detection of NDRG2/CD24 co-expression may benefit us in prediction of the prognosis in GBC.

Reduced expression of Raf kinase inhibitor protein correlates with poor prognosis in pancreatic cancer.

AIM: Raf kinase inhibitory protein (RKIP) is an inhibitor of the Raf/MEK/MAP kinase signaling cascade and a suppressor of cancer metastasis. But its function in pancreatic cancer was not yet clarified completely. The aim of this study was to investigate the involvement of RKIP in pancreatic cancer. METHODS: RKIP expression was investigated retrospectively by immunohistochemistry in paraffin-embedded primary tumor tissue samples from a series (n = 99) of consecutive patients with pancreatic cancer. Survival was calculated using Kaplan-Meier curves. Parameters found to be of prognostic significance in univariate analysis were verified in a multivariate Cox regression model. RESULTS: RKIP expression was high in normal pancreatic epithelium and retained to varying degrees in pancreatic cancer tissues. However, in tumor tissues with lymph node metastasis (P = 0.008) and high UICC stage (P = 0.006), RKIP expression was highly significantly reduced or lost. Furthermore, the reduced expression of RKIP significantly correlated with both poor overall and disease-free survival (P = 0.008 and 0.01, respectively). Multivariate analyses revealed RKIP to be an independent prognosticator. CONCLUSION: These findings suggest that RKIP could be a promising marker for predicting a better prognosis in pancreatic cancer.