Astaxanthin Rescues Memory Impairments in Rats with Vascular Dementia by Protecting Against Neuronal Death in the Hippocampus.

Vascular dementia (VaD) is a cognitive disorder characterized by a decline in cognitive function resulting from cerebrovascular disease. The hippocampus is particularly susceptible to ischemic insults, leading to memory deficits in VaD. Astaxanthin (AST) has shown potential therapeutic effects in neurodegenerative diseases. However, the mechanisms underlying its protective effects in VaD and against hippocampal neuronal death remain unclear. In this study, We used the bilateral common carotid artery occlusion (BCCAO) method to establish a chronic cerebral hypoperfusion (CCH) rat model of VaD and administered a gastric infusion of AST at 25 mg/kg per day for 4 weeks to explore its therapeutic effects. Memory impairments were assessed using Y-maze and Morris water maze tests. We also performed biochemical analyses to evaluate levels of hippocampal neuronal death and apoptosis-related proteins, as well as the impact of astaxanthin on the PI3K/Akt/mTOR pathway and oxidative stress. Our results demonstrated that AST significantly rescued memory impairments in VaD rats. Furthermore, astaxanthin treatment protected against hippocampal neuronal death and attenuated apoptosis. We also observed that AST modulated the PI3K/Akt/mTOR pathway, suggesting its involvement in promoting neuronal survival and synaptic plasticity. Additionally, AST exhibited antioxidant properties, mitigating oxidative stress in the hippocampus. These findings provide valuable insights into the potential therapeutic effects of AST in VaD. By elucidating the mechanisms underlying the actions of AST, this study highlights the importance of protecting hippocampal neurons and suggests potential targets for intervention in VaD. There are still some unanswered questions include long-term effects and optimal dosage of the use in human. Further research is warranted to fully understand the therapeutic potential of AST and its application in the clinical treatment of VaD.

Lysine butyrylation of HSP90 regulated by KAT8 and HDAC11 confers chemoresistance.

Posttranslational modification dramatically enhances protein complexity, but the function and precise mechanism of novel lysine acylation modifications remain unknown. Chemoresistance remains a daunting challenge to successful treatment. We found that lysine butyrylation (Kbu) is specifically upregulated in chemoresistant tumor cells and tissues. By integrating butyrylome profiling and gain/loss-of-function experiments, lysine 754 in HSP90 (HSP90 K754) was identified as a substrate for Kbu. Kbu modification leads to overexpression of HSP90 in esophageal squamous cell carcinoma (ESCC) and its further increase in relapse samples. Upregulation of HSP90 contributes to 5-FU resistance and can predict poor prognosis in cancer patients. Mechanistically, HSP90 K754 is regulated by the cooperation of KAT8 and HDAC11 as the writer and eraser, respectively; SDCBP increases the Kbu level and stability of HSP90 by binding competitively to HDAC11. Furthermore, SDCBP blockade with the lead compound V020-9974 can target HSP90 K754 to overcome 5-FU resistance, constituting a potential therapeutic strategy.

Genome-wide CRISPR/Cas9 screening identifies a targetable MEST-PURA interaction in cancer metastasis.

BACKGROUND: Metastasis is one of the most lethal hallmarks of esophageal squamous cell carcinoma (ESCC), yet the mechanisms remain unclear due to a lack of reliable experimental models and systematic identification of key drivers. There is urgent need to develop useful therapies for this lethal disease. METHODS: A genome-wide CRISPR/Cas9 screening, in combination with gene profiling of highly invasive and metastatic ESCC sublines, as well as PDX models, was performed to identify key regulators of cancer metastasis. The Gain- and loss-of-function experiments were taken to examine gene function. Protein interactome, RNA-seq, and whole genome methylation sequencing were used to investigate gene regulation and molecular mechanisms. Clinical significance was analyzed in tumor tissue microarray and TCGA databases. Homology modeling, modified ELISA, surface plasmon resonance and functional assays were performed to identify lead compound which targets MEST to suppress cancer metastasis. FINDINGS: High MEST expression was associated with poor patient survival and promoted cancer invasion and metastasis in ESCC. Mechanistically, MEST activates SRCIN1/RASAL1-ERK-snail signaling by interacting with PURA. miR-449a was identified as a direct regulator of MEST, and hypermethylation of its promoter led to MEST upregulation, whereas systemically delivered miR-449a mimic could suppress tumor metastasis without overt toxicity. Furthermore, molecular docking and computational screening in a small-molecule library of 1,500,000 compounds and functional assays showed that G699-0288 targets the MEST-PURA interaction and significantly inhibits cancer metastasis. INTERPRETATION: We identified the MEST-PURA-SRCIN1/RASAL1-ERK-snail signaling cascade as an important mechanism underlying cancer metastasis. Blockade of MEST-PURA interaction has therapeutic potential in management of cancer metastasis. FUNDING: This work was supported by National Key Research and Development Program of China (2021YFC2501000, 2021YFC2501900, 2017YFA0505100); National Natural Science Foundation of China (31961160727, 82073196, 81973339, 81803551); NSFC/RGC Joint Research Scheme (N_HKU727/19); Natural Science Foundation of Guangdong Province (2021A1515011158, 2021A0505030035); Key Laboratory of Guangdong Higher Education Institutes of China (2021KSYS009).

Diagnostic value of dual-energy CT and clinicopathological and imaging feature analysis of mixed endometrial stromal and smooth muscle tumors with intracardiac extension.

Objective: To describe the clinicopathological and imaging features of mixed endometrial stromal and smooth muscle tumors with intracardiac extension and to explore the diagnostic value of dual-energy computed tomography (DECT) for this rare entity. Materials and methods: This retrospective study analyzed the clinicopathological data and images of a 41-year-old female patient with pathologically documented mixed endometrial stromal and smooth muscle tumors with intracardiac extension who had undergone DECT examination. Seven virtual monoenergetic images (VMIs) in 10-kiloelectron volt (keV) intervals (range = 40-100 keV), iodine density (ID) maps, and Z effective (Zeff) maps were reconstructed, and lesion conspicuity was assessed. Tumor homology was analyzed using quantitative DECT parameters and energy spectrum attenuation curve. Results: The patient complained of a 10-day history of bilateral lower extremity edema. Computed tomography showed a hypoattenuating filling defect located within the paracervical vein that extended into the right atrium to the ventricle through the right iliac veins and inferior vena cava (IVC). Intracardiac and intravenous lesions mainly demonstrated moderate progressive enhancement, with localized non-enhancing necrotic areas on contrast-enhanced CT. Multiple nodules showing progressive enhancement (long-T1 signal, long-T2 signal) were observed at the fundus of the uterus on dynamic contrast-enhanced magnetic resonance imaging (MRI), which were deemed the primary lesions of the tumor. Overall, the tumor was characterized by a small primary lesion with extensive vascular extension. In addition, the 40 keV VMIs reconstructions were found to provide best visualization for the early detection of tumors. Conclusion: Although a definitive diagnosis of MESSMT with intracardiac extension requires confirmation by histopathological examination, imaging examination can be used to characterize the extent of the lesion. The dual-energy dataset facilitates tumor visualization and homology evaluation.

New insights into the interplay between long non-coding RNAs and RNA-binding proteins in cancer.

With the development of proteomics and epigenetics, a large number of RNA-binding proteins (RBPs) have been discovered in recent years, and the interaction between long non-coding RNAs (lncRNAs) and RBPs has also received increasing attention. It is extremely important to conduct in-depth research on the lncRNA-RBP interaction network, especially in the context of its role in the occurrence and development of cancer. Increasing evidence has demonstrated that lncRNA-RBP interactions play a vital role in cancer progression; therefore, targeting these interactions could provide new insights for cancer drug discovery. In this review, we discussed how lncRNAs can interact with RBPs to regulate their localization, modification, stability, and activity and discussed the effects of RBPs on the stability, transport, transcription, and localization of lncRNAs. Moreover, we explored the regulation and influence of these interactions on lncRNAs, RBPs, and downstream pathways that are related to cancer development, such as N6-methyladenosine (m6A) modification of lncRNAs. In addition, we discussed how the lncRNA-RBP interaction network regulates cancer cell phenotypes, such as proliferation, apoptosis, metastasis, drug resistance, immunity, tumor environment, and metabolism. Furthermore, we summarized the therapeutic strategies that target the lncRNA-RBP interaction network. Although these treatments are still in the experimental stage and various theories and processes are still being studied, we believe that these strategies may provide new ideas for cancer treatment.

Targeting PI3K/Akt signal transduction for cancer therapy.

The phosphatidylinositol 3-kinase (PI3K)/Akt pathway plays a crucial role in various cellular processes and is aberrantly activated in cancers, contributing to the occurrence and progression of tumors. Examining the upstream and downstream nodes of this pathway could allow full elucidation of its function. Based on accumulating evidence, strategies targeting major components of the pathway might provide new insights for cancer drug discovery. Researchers have explored the use of some inhibitors targeting this pathway to block survival pathways. However, because oncogenic PI3K pathway activation occurs through various mechanisms, the clinical efficacies of these inhibitors are limited. Moreover, pathway activation is accompanied by the development of therapeutic resistance. Therefore, strategies involving pathway inhibitors and other cancer treatments in combination might solve the therapeutic dilemma. In this review, we discuss the roles of the PI3K/Akt pathway in various cancer phenotypes, review the current statuses of different PI3K/Akt inhibitors, and introduce combination therapies consisting of signaling inhibitors and conventional cancer therapies. The information presented herein suggests that cascading inhibitors of the PI3K/Akt signaling pathway, either alone or in combination with other therapies, are the most effective treatment strategy for cancer.

Computed Tomography Features and Clinicopathological Characteristics of Gastric Sarcomatoid Carcinoma.

PURPOSE: Gastric sarcomatoid carcinoma (GSC) is a very rare malignant tumor. The purpose of this study is to describe the clinical, computed tomography (CT), and pathologic features of GSC to increase awareness of this entity. METHODS: The CT features and clinical data of five patients with pathologically documented GSC were retrospectively analyzed and compared with the corresponding data of gastric adenocarcinoma and lymphoma. RESULTS: Among the 5 patients, 4 were male, and 1 was female. The median age was 59 years. Of the 5 cases of GSC, 3 were in the gastric fundus and cardia, 1 was in the gastric body, and 1 was in the gastric fundus. The gastric wall had local thickening in 4 cases and mass formation in 1 case, with stenosis and deformation of the adjacent gastric cavity. The long-axis diameter of the lesions ranged from 1.4 to 10.2 cm (mean, 4.97 cm) and was <10 cm in 4 cases and >10 cm in 1 case. The tumor showed predominantly inhomogeneous density, with radiodensity values ranging from 30 to 53 HU. In addition, ulcers with an irregular base and slightly raised borders were observed in 4 of 5 cases. After an injection of contrast material, heterogeneous (n = 4) or homogeneous (n = 1) enhancement was observed. After contrast medium injection, obvious enhancement was seen in 2 cases, and moderate enhancement was seen in 3 cases; the peak tumor signal was observed in the portal phase. Two of the patients demonstrated evidence of lymph node involvement, and in one patient, the boundary between the lesion and the left lobe of the liver was unclear, with low attenuation in the right lobe of the liver with circular enhancement. The remaining two patients showed no evidence of metastasis. CONCLUSION: Although GSC is extremely rare, it should be considered in the differential diagnosis of gastric adenocarcinoma and lymphoma. CT findings, combined with patient age and sex, can provide support for the diagnosis of GSC. However, the final diagnosis must be confirmed with histopathology.

ciRS-7 Promotes the Proliferation and Migration of Papillary Thyroid Cancer by Negatively Regulating the miR-7/Epidermal Growth Factor Receptor Axis.

PURPOSE: The incidence of papillary thyroid cancer (PTC) is increasing, and traditional diagnostic methods are unsatisfactory. Therefore, identifying novel prognostic markers is very important. ciRS-7 has been found to play an important role in many cancers, but its role in PTC has not been reported. This study was performed to evaluate the biological role and mechanism of ciRS-7 in PTC. Material and Methods. The expression of ciRS-7 in PTC tissues and the matched adjacent tissues was determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The PTC cell lines (TPC-1 and BCPAP) were used to evaluate the role of ciRS-7. ciRS-7-siRNA and overexpression plasmid were constructed and transfected into PTC cells. A CCK-8 assay and colony formation assay were performed to explore the effects of ciRS-7 on cell proliferation. Annexin V/PI staining and FACS detection were used to detect cell apoptosis. Wound healing assay was performed to detect cell migration. A transwell assay was conducted to explore the effects of ciRS-7 on invasion and migration. Western blotting was performed to evaluate protein expression. The luciferase reporter system was used to determine the underlying mechanism of miR-7. RESULT: ciRS-7 was highly expressed in PTC tissues and cell lines compared with the corresponding controls. In vitro study showed that ciRS-7 silencing suppressed proliferation, migration, and invasion of TPC-1 and BCPAP. Mechanistically, the effects of ciRS-7 on invasion and migration may be related to epithelial-mesenchymal transition (EMT). ciRS-7 silencing could attenuate effects on PTC cells induced by miR-7 knockdown. Epidermal growth factor receptor (EGFR), which was demonstrated to be a target of miR-7, decreased significantly in ciRS-7-siRNA PTC cells. Overexpression of EGFR also attenuated effects of PTC cells induced by silencing ciRS-7. CONCLUSION: ciRS-7 was significantly upregulated in PTC tissues, and it promoted the progression of PTC by regulating the miR-7/EGFR axis. ciRS-7 is a promising prognostic biomarker and therapeutic target in PTC.

Meningioma in mature cystic teratoma of the ovary: clinical and computed tomography findings.

BACKGROUND: Mature cystic teratoma (MCT) with meningioma of the ovary is a very rare benign tumor. There is only 3 reports of this disease until June 2019. The aim of the present study was to describe a ovarian mature cystic teratoma containing meningioma and nests of neuroblasts in a 15-year-old girl. METHODS: The method used in the present study consists of description of the clinical history, image lab features, and pathological result. RESULTS: The patient complained of a 2-month history of irregular vaginal bleeding. Abdominal computed tomography (CT) showed a large oval cystic-solid mass with septations and fat density shadow, in abdomen pelvic cavity. The cystic part was the main component in the mass. The tumoral solid parts and its internal division could be seen intensified from slight to moderate on contrast-enhanced CT images compared with those on precontrast images, and the solid parts showed heterogeneous enhancement. Neighbouring intestinal tract and the uterus displaced by compression. The pathological examination confirmed the diagnosis. CONCLUSIONS: The clinical feature of ovarian mature cystic teratoma with meningioma includes a lack of specificity. Only meticulous recording of the gross features, histopathological examination including immunohistochemistry and supportive clinical and radiological findings to arrive at a correct diagnosis in case of unconventional tumours. If necessary, preoperative puncture can be performed.

MicroRNA-134 prevents the progression of esophageal squamous cell carcinoma via the PLXNA1-mediated MAPK signalling pathway.

BACKGROUND: MicroRNAs (miRNAs) are involved in oncogenesis of esophageal squamous cell carcinoma (ESCC). miR-134 is reported to have a tumour-suppressive role but its role in ESCC is not known. The present study was designed to examine whether miR-134 inhibits ESCC development and further explored relevant underlying mechanisms. METHODS: Differentially expressed genes related to ESCC were identified from microarray gene expression profiles. Immunohistochemical staining and RT-qRCR assays identified elevated PLXNA1 expression levels and low miR-134. The relationship between miR-134 and PLXNA1 was predicted and further verified by a dual-luciferase reporter assay. The expression levels of miR-134 and PLXNA1 in ESCC cells were modified by miR-134 mimic/inhibitor and siRNA against PLXNA1, respectively. Thereafter, the expression of MAPK signalling pathway-related proteins, as well as the viability, migration, invasion, cell cycle and cell apoptosis of ESCC cells was investigated. FINDINGS: The results showed that miR-134 could block the MAPK signalling pathway by downregulating PLXNA1. When miR-134 was overexpressed or PLXNA1 was silenced, cell apoptosis was enhanced, the cell cycle was retarded, and the cell proliferation, migration and invasion were suppressed. In vivo experiments confirmed that miR-134 overexpression or PLXNA1 silencing restrained tumour growth and lymph node metastasis. INTERPRETATION: These findings demonstrate that cancer cell proliferation, migration, invasion, and tumour metastasis of ESCC can be suppressed by overexpression of miR-134 through downregulating PLXNA1, which subsequently blocks the MAPK signalling pathway. These results provide new potential targets and strategies for the treatment of ESCC.

CT findings and clinical features of Epstein-Barr virus-associated lymphoepithelioma-like gastric carcinoma.

Epstein-Barr virus (EBV)-associated lymphoepithelioma-like gastric carcinoma (LELGC) is a rare primary stomach tumor, which has overlapping imaging features with mass forming gastric carcinoma (GC). The aim of our study was to present the computed tomography (CT) findings and clinical features of EBV-associated LELGC to increase awareness of this entity.The CT findings and clinical features of 4 patients with pathologically documented EBV-associated LELGC were retrospectively analyzed.Among the 4 patients, 3 were male, and 1 was female. The medium age was 51 years old. All cases were single lesions including 1 was in the gastric cardia, 1 was in the gastric body, and 2 were in the gastric antrum. A focal thickening of the gastric wall was conducted, with a large thickness-to-length ratio. The low-density stripe of the normal gastric wall abruptly terminated at the edge of the lesion. The CT images of 4 cases showed inhomogeneous density with the radiodensity values ranging from 25 to 48 HU. In addition, an ulcer was demonstrated with an irregular base and slightly raised borders in all cases. Enhancement after injection of contrast material was heterogeneous enhancement (n = 3) or homogeneous (n = 1). After enhancement, obvious enhancement was seen in 1 case, moderate enhancement was seen in 3 cases, with the peak value of the tumor in the portal phase. No evidence of lymph node involvement and distant invasion was observed.Although LELGC is quite rare, it should be considered in differential diagnosis of early GC, advanced GC, and lymphoma. The relatively typical CT appearance, combined the age and sex of patients, can suggest the diagnosis of LELGC.

Downregulation of circDYNC1H1 exhibits inhibitor effect on cell proliferation and migration in hepatocellular carcinoma through miR-140-5p.

Circular RNAs have been found to be aberrantly expressed in tumors and their significance in tumorigenesis has been focused on. The role of circDYNC1H1 in hepatocellular carcinoma (HCC) pathogenesis and its relationship with miR-140-5p were explored. The expression of circDYNC1H1, miR-140-5p, and SULT2B1 in HCC tissues and cells was measured, and Pearson's analysis was used to analyze their expression correlation. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and Transwell assays were performed to determine cell proliferation and migration. Binding between circDYNC1H1 and miR-140-5p was evaluated with RNA pull-down assay. A luciferase reporter assay was conducted to assess the interaction between circDYNC1H1 and miR-140-5p and between miR-140-5p and SULT2B1. circDYNC1H1 was highly expressed in HCC tissues (n = 20), and it was negatively associated with the expression of miR-140-5p but positively correlated with SULT2B1 messenger RNA expression. circDYNC1H1 was upregulated in cell lines of HCC. Interference of circDYNC1H1 suppressed cell proliferation and migration of HCC. circDYNC1H1 acted as a sponge of miR-140-5p. miR-140-5p controlled SULT2B1 expression by targeting its 3'-untranslated region. circDYNC1H1 enhanced SULT2B1 expression via sponging miR-140-5p. Downregulation of circDYNC1H1 disturbed cell proliferation and migration of HCC through miR-140-5p/SULT2B1 pathway. Silencing of circDYNC1H1 delayed tumor growth in HCC mouse model. Acting like a sponge of miR-140-5p, silenced circDYNC1H1 downregulated SULT2B1 to restrain HCC cell proliferation and migration, which is adverse to HCC growth and progression.

The synergistic effect of esophageal squamous cell carcinoma KYSE150 cells and M2 macrophages on lymphatic endothelial cells.

Objective: This study aimed to investigate whether tumor-associated macrophages (TAMs) and esophageal squamous cell carcinoma (ESCC) cells could synergistically influence the generation of lymphatic vessels via the VEGF-C/VEGFR-3 signaling pathway and to address its mechanism. Methods: M2 macrophages were sorted with immunomagnetic beads and induced in vitro. VEGF-C siRNA plasmids were constructed and transfected into M2 macrophages and the ESCC cell line KYSE150. Different conditioned culture media before and after transfection were collected and classified into different groups for culturing ESCC-associated lymphatic endothelial cells (ESCC-LECs). Using the CCK-8 assay, Transwell cell migration assay and Matrigel three-dimensional culture, the proliferation, migration and ring forming abilities of ESCC-LECs before and after transfection were compared, respectively. With ELISA, western blot and q(RT)-PCR, VEGF-C concentrations in conditioned culture media and the protein and mRNA expression levels of VEGFR-3 in LECs before and after transfection were compared, respectively. Results: Before transfection, ESCC-LECs in the group with mixed culture medium had stronger proliferation, migration and ring forming abilities than the other groups. The VEGF-C concentration and VEGFR-3 protein and mRNA expression levels were higher in the mixed culture medium group than in the other groups. After transfection, all indices were the lowest in the mixed culture medium group. Conclusions: M2 macrophages can enhance the proliferation, migration and ring forming abilities of ESCC-LECs. ESCC cells and M2 macrophages have synergistic effects on the proliferation, migration and ring forming abilities of ESCC-LECs. VEGF-C siRNA can inhibit the proliferation, migration and ring forming abilities of ESCC-LECs by silencing the expression of VEGF-C and its receptor VEGFR-3 in KYSE150 cells and M2 macrophages.

Iodine Concentration in Spectral CT: Assessment of Prognostic Determinants in Patients With Gastric Adenocarcinoma.

OBJECTIVE: The purpose of this study was to use virtual monochromatic spectral CT to investigate the usefulness of iodine concentration (IC) and its correlation with clinicopathologically determined prognostic factors in gastric adenocarcinoma. SUBJECTS AND METHODS: From June 2012 to March 2015, 34 patients with gastric adenocarcinoma underwent arterial and portal venous phase spectral CT. The ICs in the arterial and portal venous phases were calculated and then normalized with the aorta as normalized IC (NIC). The surgical specimen was evaluated with CD34 staining to determine microvessel density (MVD). The correlation between imaging results and clinicopathologic findings was investigated for histologic grading, lymph node metastasis, serosal involvement, distant metastasis, pathologic TNM stage, and MVD. RESULTS: The mean arterial phase NIC value of tumors was 0.12 ± 0.03, portal venous phase NIC value was 0.39 ± 0.06, and MVD was 26.94 ± 7.87 vessels per high-power field (×400). Both arterial phase and portal venous phase NIC values were significantly higher in poorly differentiated gastric adenocarcinomas (p = 0.005) than in moderately differentiated tumors (p = 0.013). There was no significant correlation between NIC and serosal involvement or distant metastasis. There was significant correlation between the NIC and MVD in gastric adenocarcinoma (arterial phase NIC, p = 0.013; portal venous phase NIC, p = 0.001). However, neither the arterial nor the portal venous phase NIC of gastric adenocarcinoma had a significant relation to lymphatic metastasis or pathologic TNM stage. There was a significant difference between the high and low MVD groups with respect to portal venous phase NIC (p = 0.045). CONCLUSION: NIC can serve as a useful predictor of angiogenesis and degree of differentiation of moderately and poorly differentiated gastric adenocarcinomas.

Spectral computed tomography in advanced gastric cancer: Can iodine concentration non-invasively assess angiogenesis?

AIM: To investigate the correlation of iodine concentration (IC) generated by spectral computed tomography (CT) with micro-vessel density (MVD) and vascular endothelial growth factor (VEGF) expression in patients with advanced gastric carcinoma (GC). METHODS: Thirty-four advanced GC patients underwent abdominal enhanced CT in the gemstone spectral imaging mode. The IC of the primary lesion in the arterial phase (AP) and venous phase (VP) were measured, and were then normalized against that in the aorta to provide the normalized IC (nIC). MVD and VEGF were detected by immunohistochemical assays, using CD34 and VEGF-A antibodies, respectively. Correlations of nIC with MVD, VEGF, and clinical-pathological features were analyzed. RESULTS: Both nICs correlated linearly with MVD and were higher in the primary lesion site than in the normal control site, but were not correlated with VEGF expression. After stratification by clinical-pathological subtypes, nIC-AP showed a statistically significant correlation with MVD, particularly in the group with tumors at stage T4, without nodular involvement, of a mixed Lauren type, where the tumor was located at the antrum site, and occurred in female individuals. nIC-VP showed a positive correlation with MVD in the group with the tumor at stage T4 and above, had nodular involvement, was poorly differentiated, was located at the pylorus site, of a mixed and diffused Lauren subtype, and occurred in male individuals. nIC-AP and nIC-VP showed significant differences in terms of histological differentiation and Lauren subtype. CONCLUSION: The IC detected by spectral CT correlated with the MVD. nIC-AP and nIC-VP can reflect angiogenesis in different pathological subgroups of advanced GC.

Suppression of microRNA-9-5p rescues learning and memory in chronic cerebral hypoperfusion rats model.

Chronic cerebral hypoperfusion has been associated with cognitive impairment in dementias, such as Alzheimer's disease (AD) and vascular disease (VaD), the two most common neurodegenerative diseases in aged people. However, the effective therapeutic approaches for both AD and VaD are still missing. MicroRNAs (miRNAs) are small non-coding RNAs that play important roles in the epigenetic regulation in many neurological disorders; the critical roles of miRNAderegulation had been implicated in both AD and VaD. In the current study, we reported that miR-9-5p is elevated in the serum and cerebrospinalfluid of patientswith VaD. The miR-9-5p wasalso increased in both the hippocampus and cortex of rats with 2-vessel occlusionsurgery. Furthermore, application ofmiR-9-5p antagomirs attenuated the memory impairments in rats with 2-vessel occlusion surgery both in the Morris water maze and inhibitory avoidance step-down tasks. Furthermore, miR-9-5p antagomirs reducedthe inhibition oflong-term potentiation and loss of dendritic spines in chronic cerebral hypoperfusionrats. Additionally, the cholinergic neuronal function was rescued by miR-9-5p antagomirs, as well as the neuronal loss and the oxidative stress. We concluded that miR-9-5p inhibition may be a potential therapeutic target for the memory impairments caused by chronic cerebral hypoperfusion.

Association analysis of genetic variants of adiponectin gene and risk of pancreatic cancer.

Adiponectin is a cytokine exclusively secreted from adipocyte, and could perform direct or indirect effects on anti-inflammation and anti-tumor. Previous researches have studied the correlation between plasma adiponectin levels and the risk of pancreatic cancer. So we aimed at investigating the association of genetic variants of adiponectin gene and the risk of pancreatic cancer. In this study, we genotyped 6 SNPs of adiponectin gene in a case-control study of recruited 172 patients of pancreatic cancer and 181 healthy people in Chinese Han population. The results indicated that two of the SNPs had significant associations with pancreatic cancer. Of which, the SNP rs1501299C>A decreased the risk of PC (P=0.016, OR=0.662 95% CI 0.472-0.928), while rs1065358T>C increased the risk of PC (P=0.027, OR=1.421 95% CI 1.040-1.941). Furthermore, in the clinical correlation analysis, we found rs1501299 was correlated with tumor size (P=0.026), cigarette smoking (P=0.022) and alcohol consumption (P=0.001) and rs1063538 was correlated with alcohol consumption (P=0.026). In conclusion, we provided evidences that the variants in adiponectin gene might influence the development and progression of pancreatic cancer.