A study on the role of serum uric acid in differentiating acute inflammatory demyelinating polyneuropathy from acute-onset chronic inflammatory demyelinating polyneuropathy.

BACKGROUND AND PURPOSE: Clinical symptoms and laboratory indices for acute inflammatory demyelinating polyneuropathy (AIDP), a variant of Guillain-Barré syndrome, and acute-onset chronic inflammatory demyelinating polyneuropathy (A-CIDP) were analyzed to identify factors that could contribute to early differential diagnosis. METHODS: A retrospective chart review was performed on 44 AIDP and 44 A-CIDP patients looking for any demographic characteristics, clinical manifestations or laboratory parameters that might differentiate AIDP from acutely presenting CIDP. RESULTS: In Guillain-Barré syndrome patients (N = 63), 69.84% (N = 44) were classified as having AIDP, 19.05% (N = 12) were found to have acute motor axonal neuropathy, 6.35% (N = 4) were found to have acute motor and sensory axonal neuropathy, and 4.76% (N = 3) were found to have Miller Fisher syndrome. Serum uric acid (UA) was higher in A-CIDP patients (329.55 ± 72.23 µmol/L) than in AIDP patients (221.08 ± 71.32 µmol/L) (p = 0.000). Receiver operating characteristic analyses indicated that the optimal UA cutoff was 283.50 µmol/L. Above this level, patients were more likely to present A-CIDP than AIDP (specificity 81.80%, sensitivity 81.80%). During the follow-up process, serum samples were effectively collected from 19 AIDP patients during the rehabilitation phase and 28 A-CIDP patients during the remission stage, and it was found that UA levels were significantly increased in A-CIDP (remission) (298.9 ± 90.39 µmol/L) compared with AIDP (rehabilitation) (220.1 ± 108.2 µmol/L, p = 0.009). CONCLUSION: These results suggest that serum UA level can help to differentiate AIDP from A-CIDP with high specificity and sensitivity, which is helpful for early diagnosis and guidance of treatment.

Does dual antiplatelet therapy increase the risk of haematoma enlargement in the acute stage? A retrospective study of the use of stent-assisted coiling versus coiling alone or balloon-assisted coiling for the treatment of ruptured intracranial aneurysms combined with intracranial haematoma.

This study aims to identify the efficacy and safety of stent-assisted coiling (SAC) treatment of ruptured intracranial aneurysms (RIAs) combined with intracranial haematoma (ICH) compared to coiling alone or balloon-assisted coiling (non-SAC). A retrospective analysis of 54 consecutive patients receiving endovascular therapy from 2014 to 2020 was performed. The data collected included baseline characteristics, angiographic results, perioperative complications, immediate aneurysm occlusion, clinical outcomes, follow-up at discharge and after 6 months, hospitalisation costs, and inpatient length of stay. Patients were categorised into the SAC group and the non-SAC group. Univariate and multivariate logistic regression analyses were used to identify risk factors related to clinical outcomes. Of the 54 patients harbouring RIAs with ICH, 22 (40.74%) and 32 (59.26%) patients were subject to SAC and non-SAC treatments, respectively. Postoperative rebleeding (1 [4.5%] and 3 [9.3%] in SAC and non-SAC groups, respectively, p > 0.05) and Hunt-Hess grade (IV-V) lesions (13.6% vs. 40.6%, p = 0.067) did not differ between the two groups. In total, 10 (45.5%) patients treated with SAC received a Fisher scale score of 0-3 compared with 6 (18.8%) patients treated with non-SAC methods (p = 0.035). Compared with the non-SAC group (7/21.9%), the rate of wide-necked aneurysms was increased in the SAC group (11/50%) (p = 0.031). No differences in poor outcomes (mRS > 2) were noted between the SAC and non-SAC groups (p > 0.05). Multivariate analysis revealed that ischaemic complication events (p = 0.016) represent the only independent risk factor for adverse outcomes, and a trend towards unfavourable clinical outcomes was noted for patients who smoke (p = 0.087). SAC is a safe and efficient treatment for RIAs combined with ICH when dual antiplatelet therapy (DAPT) is used in the perioperative period. In addition, SAC should be preferentially used in wide-neck RIAs. Ischaemic complications are a risk factor for poor clinical outcomes. Given the small sample size and retrospective bias of this study, these findings should be further verified in a study with a larger sample size or a randomised controlled trial (RCT).

Roles of Fibroblast Growth Factors in the Axon Guidance.

Fibroblast growth factors (FGFs) have been widely studied by virtue of their ability to regulate many essential cellular activities, including proliferation, survival, migration, differentiation and metabolism. Recently, these molecules have emerged as the key components in forming the intricate connections within the nervous system. FGF and FGF receptor (FGFR) signaling pathways play important roles in axon guidance as axons navigate toward their synaptic targets. This review offers a current account of axonal navigation functions performed by FGFs, which operate as chemoattractants and/or chemorepellents in different circumstances. Meanwhile, detailed mechanisms behind the axon guidance process are elaborated, which are related to intracellular signaling integration and cytoskeleton dynamics.

Biomimetic Nanoplatelets to Target Delivery Hirudin for Site-Specific Photothermal/Photodynamic Thrombolysis and Preventing Venous Thrombus Formation.

Due to the high recurrence rate and mortality of venous thrombosis, there is an urgent need for research on antithrombotic strategies. Because of the short half-life, poor targeting capabilities, bleeding complications, and neurotoxic effects of conventional pharmacological thrombolysis methods, it is essential to develop an alternative strategy to noninvasive thrombolysis and decrease the recurrence rate of venous thrombosis. A platelet-mimetic porphyrin-based covalent organic framework-engineered melanin nanoplatform, to target delivery of hirudin to the vein thrombus site for noninvasive thrombolysis and effective anticoagulation, is first proposed. Owing to the thrombus-hosting properties of platelet membranes, the nanoplatform can target the thrombus site and then activate hyperthermia and reactive oxygen species for thrombolysis under near-infrared light irradiation. The photothermal therapy/photodynamic therapy combo can substantially improve the effectiveness (85.7%) of thrombolysis and prevent secondary embolism of larger fragments. Afterward, the highly loaded (97%) and slow-release hirudin (14 days) are effective in preventing the recurrence of blood clots without the danger of thrombocytopenia. The described biomimetic nanostructures offer a promising option for improving the efficacy of thrombolytic therapy and reducing the risk of bleeding complications in thrombus associated diseases.

DNA-PKcs participated in hypoxic pulmonary hypertension.

BACKGROUND: Hypoxic pulmonary hypertension (HPH) is a common complication of chronic lung disease, which severely affects the survival and prognosis of patients. Several recent reports have shown that DNA damage and repair plays a crucial role in pathogenesis of pulmonary arterial hypertension. DNA-dependent protein kinase catalytic subunit (DNA-PKcs) as a part of DNA-PK is a molecular sensor for DNA damage that enhances DSB repair. This study aimed to demonstrate the expression and potential mechanism of DNA-PKcs on the pathogenesis of HPH. METHODS: Levels of DNA-PKcs and other proteins in explants of human and rats pulmonary artery from lung tissues and pulmonary artery smooth muscle cells (PASMC) were measured by immunohistochemistry and western blot analysis. The mRNA expression levels of DNA-PKcs and NOR1 in PASMCs were quantified with qRT-PCR. Meanwhile, the interaction among proteins were detected by Co-immunoprecipitation (Co-IP) assays. Cell proliferation and apoptosis was assessed by cell counting kit-8 assay(CCK-8), EdU incorporation and flow cytometry. Rat models of HPH were constructed to verify the role of DNA-PKcs in pulmonary vascular remodeling in vivo. RESULTS: DNA-PKcs protein levels were both significantly up-regulated in explants of pulmonary artery from HPH models and lung tissues of patients with hypoxemia. In human PASMCs, hypoxia up-regulated DNA-PKcs in a time-dependent manner. Downregulation of DNA-PKcs by targeted siRNA or small-molecule inhibitor NU7026 both induced cell proliferation inhibition and cell cycle arrest. DNA-PKcs affected proliferation by regulating NOR1 protein synthesis followed by the expression of cyclin D1. Co-immunoprecipitation of NOR1 with DNA-PKcs was severely increased in hypoxia. Meanwhile, hypoxia promoted G2 + S phase, whereas the down-regulation of DNA-PKcs and NOR1 attenuated the effects of hypoxia. In vivo, inhibition of DNA-PKcs reverses hypoxic pulmonary vascular remodeling and prevented HPH. CONCLUSIONS: Our study indicated the potential mechanism of DNA-PKcs in the development of HPH. It might provide insights into new therapeutic targets for pulmonary vascular remodeling and pulmonary hypertension.

circ-BPTF serves as a miR-486-5p sponge to regulate CEMIP and promotes hypoxic pulmonary arterial smooth muscle cell proliferation in COPD.

Hypoxia plays a crucial role in pulmonary vascular remodelling at the early stage of chronic obstructive pulmonary disease (COPD). Circle RNA (circRNA) has been identified to play a critical role in multiple diseases. However, the role of circRNAs in pulmonary vascular remodelling in COPD remains unclear. In this study, we aim to investigate the role of circRNAs in pulmonary arterial smooth muscle cell proliferation and pulmonary vascular remodelling in COPD. COPD patients show lower partial pressure of arterial oxygen and pulmonary arterial remodeling as compared with controls. circRNA microarray and real-time PCR analyses show significantly higher level of circ-BPTF and lower miR-486-5p level in the pulmonary arteries of COPD patients as compared with controls. Hypoxia suppresses miR-486-5p expression but promotes expressions of circ-BPTF and cell migration inducing protein (CEMIP) in human pulmonary arterial smooth muscle cells (PASMCs) in vitro. Loss- and gain-of-function experiments show that circ-BPTF promotes PASMC proliferation in vitro. Moreover, luciferase reporter assay results indicate that circ-BPTF regulates PASMC proliferation by acting as an miR-486-5p sponge. CEMIP is identified as a candidate target gene of miR-486-5p by luciferase reporter assay. Overall, our study shows that circ-BPTF serves as a miR-486-5p sponge to regulate CEMIP and promote hypoxic PASMC proliferation in pulmonary vascular remodelling in COPD.

Piperine Improves Lipid Dysregulation by Modulating Circadian Genes Bmal1 and Clock in HepG2 Cells.

Metabolic disorders are closely associated with the dysregulation of circadian rhythms. Many bioactive components with lipid metabolism-regulating effects have been reported to function through circadian clock-related mechanisms. As the main pungent principle of black pepper, piperine (PIP) has been demonstrated to possess anti-obesity bioactivity by affecting hepatic lipid metabolism-related factors. However, whether the circadian clock genes Bmal1 and Clock are involved in the protective effect of PIP against lipid metabolism disorders remains unknown. In this work, oleic acid (OA) induced lipid accumulation in HepG2 cells. The effect of PIP on redox status, mitochondrial functions, and circadian rhythms of core clock genes were evaluated. Results revealed that PIP alleviated circadian desynchrony, ROS overproduction, and mitochondrial dysfunction. A mechanism study showed that PIP could activate the SREBP-1c/PPARγ and AMPK/AKT-mTOR signaling pathways in a Bmal1/Clock-dependent manner in HepG2 cells. These results indicated that Bmal1 and Clock played important roles in the regulating effect of PIP on hepatic lipid homeostasis.

Miniature Hollow Gold Nanorods with Enhanced Effect for In Vivo Photoacoustic Imaging in the NIR-II Window.

The miniaturization of gold nanorods exhibits a bright prospect for intravital photoacoustic imaging (PAI) and the hollow structure possesses a better plasmonic property. Herein, miniature hollow gold nanorods (M-AuHNRs) (≈46 nm in length) possessing strong plasmonic absorbance in the second near-infrared (NIR-II) window (1000-1350 nm) are developed, which are considered as the most suitable range for the intravital PAI. The as-prepared M-AuHNRs exhibit 3.5 times stronger photoacoustic signal intensity than the large hollow Au nanorods (≈105 nm in length) at 0.2 optical density under 1064 nm laser irradiation. The in vivo biodistribution measurement shows that the accumulation in tumor of miniature nanorods is twofold as high as that of the large counterpart. After modifying with a tumor-targeting molecule and fluorochrome, in living tumor-bearing mice, the M-AuHNRs group gives a high fluorescence intensity in tumors, which is 3.6-fold that of the large ones with the same functionalization. Moreover, in the intravital PAI of living tumor-bearing mice, the M-AuHNRs generate longer-lasting and stronger photoacoustic signal than the large counterpart in the NIR-II window. Overall, this study presents the fabrication of M-AuHNRs as a promising contrast agent for intravital PAI.

Resveratrol prevented experimental pulmonary vascular remodeling via miR-638 regulating NR4A3/cyclin D1 pathway.

OBJECTIVE: Resveratrol has shown benefit for pulmonary hypertension improvement. Our previous reports showed NR4A3/cyclin D1 pathway promoted pulmonary arterial smooth muscle cells (PASMCs) proliferation. This study tried to explore the mechanism underlying this process, focusing on the role of resveratrol in regulation of miRNA and NR4A3. METHODS: Rats were injected with monocrotaline (MCT) to establish pulmonary hypertension (PH) models. Resveratrol was used to prevent pulmonary vascular remodeling. Primary rat PASMCs were cultured in vitro and stimulated by platelet-derived growth factor (PDGF) with or without resveratrol. Cells proliferation and expression of miR-638 as well as NR4A3 were evaluated. RESULTS: MCT resulted in significant pulmonary vascular remodeling and down-regulation of miR-638, which could be suppressed by resveratrol. Moreover, PDGF-induced PASMC proliferation and miR-638 down-regulation were both significantly prevented by resveratrol treatment in vitro. MiR-638 mimics markedly inhibited PASMC proliferation and percentage of PCNA-positive cells in vitro. But anti-miR-638 could markedly promote cells proliferation and percentage of PCNA-positive cells. The luciferase reporter assay showed that NR4A3 was a direct target of miR-638. The loss-of-function and gain-of-function experiments indicated that NR4A3 promoted proliferation via cyclin D1 pathway. CONCLUSION: Our data indicated that resveratrol prevented MCT-induced pulmonary vascular remodeling via miR-638 regulating NR4A3/cyclin D1 pathway.

[Toxic effects of AFB_1/T-2 toxin and intervention effects of Meyerozyma guilliermondii in dried Lutjanus erythopterus on mice].

OBJECTIVE: In order to investigate the effect of yeast on reducing mycotoxin damage in dried fish. METHODS: A strain of Meyerozyma guilliermondii MH 211588. 1(MG-81) was mixed and fermented 48 h with dried Lutjanus erythopterus which contaminated aflatoxin B_1(AFB_1) and T-2 toxin(T-2). The toxin concentration in fermentation at different time was detected by LC-MS/MS, and fermentation was fed with mice by intragastric administration(7 d). Blood routine and four liver function enzymes were measured by hematology analyzer and microplate spectrophotometer respectively. The elimination effect of MG-81 isolate on mycotoxin damage in dried fish was evaluated by the toxin concentration at different time and its toxic effect on mice. RESULTS: The removal rates of AFB_1 and T-2 in dried fish fermentation showed a parabolic linear growth trend with the prolongation of fermentation time. The removal rates of AFB_1 and T-2 in dried fish fermentation broth tended to be stable at 36 h(the removal rates of AFB_1 and T-2 were 83. 7%±1. 3% and 78. 5%±0. 8%). This indicated that 36 h was the optimal time for MG-81 to remove mycotoxins in dried fish. At the same time, it was found that there was no significant change in the indexes of MG-81 dried fish fermentation compared with the control group(P>0. 05), while the same dose of AFB_1 and T-2 dried fish fermentation(without MG-81), the leucocytes, lymphocytes, erythrocyte, hemoglobin, platelet and mean platelet volume of mice were significantly lower than those of control group(P>0. 05), showing obvious hemotoxicity and immunotoxicity. The activity of four liver enzymes was increased significantly(P<0. 05), showing obvious hepatotoxicity. CONCLUSION: The fermentation of MG-81 for 36 h can effectively remove AFB_1 and T-2 from dried fish and eliminate their hazards.

Glutamate Ionotropic Receptor Kainate Type Subunit 3 (GRIK3) promotes epithelial-mesenchymal transition in breast cancer cells by regulating SPDEF/CDH1 signaling.

Glutamate Ionotropic Receptor Kainate Type Subunit 3 (GRIK3) is an important excitatory neurotransmitter receptor that plays a significant role in various neurodegenerative diseases. However, the biological functions of GRIK3 in malignancies are largely unknown because of limited related studies. Here, we primarily reported that the expression of GRIK3 was higher in breast cancer tissues than in adjacent noncancerous tissues. GRIK3 expression was also positively correlated with the prognosis of patients with breast cancer. GRIK3 promoted the proliferation and migration abilities of breast cancer cells and enhanced the growth of orthotopically implanted tumors. Mechanically, GRIK3 influenced a range of signaling pathways and key signal transducers, including two epithelial-mesenchymal transition regulators, SPDEF and CDH1. Heterogenous expression of SPDEF and CDH1 counteracted the migration and invasion abilities, respectively, of breast cancer cells induced by GRIK3. Moreover, overexpression of GRIK3 increased the expression of mesenchymal markers and decreased the expression of epithelial markers, resulting in the translocation of ß-catenin into the nucleus and the increased ß-catenin transcriptional activity. In conclusion, the present study reported a novel oncogenic role of GRIK3. Meanwhile, GRIK3, as a membrane receptor, may also serve as a potential therapeutic target for the treatment of breast cancer.

Characterization of monocytic and granulocytic subsets of myeloid-derived suppressor cells in blood donors with occult hepatitis B virus infection.

Myeloid-derived suppressor cells (MDSCs) accumulate from many diseases. MDSCs are rarely explored in occult hepatitis B virus infection (OBI). The frequency of monocytic MDSCs (M-MDSCs) and granulocytic MDSCs (G-MDSCs) in OBI carriers was analyzed for correlation with clinical parameters, which was no different between OBI and healthy individuals, whereas the frequency of M-MDSCs but G-MDSCs in OBI was significantly lower than that observed in chronic hepatitis B carriers (0.4% vs 0.7%, P = 0.0004). The frequency of MDSCs was not correlated with clinical parameters and viral load of OBI, suggesting that the absence of HBsAg in OBI carriers might not induce the accumulation of MDSCs.

A signal amplification system on a lateral flow immunoassay detecting for hepatitis e-antigen in human blood samples.

Hepatitis B e-antigen (HBeAg) is the secretory form of the nucleocapsid of the hepatitis B virus (HBV), which is a marker of viral replication. In this study, a novel signal amplification system (SAS) based on the lateral flow immunoassay (LFIA) was used for rapid detection of HBeAg in blood samples from patients or blood donors. In this assay, the detection antibody was conjugated with gold nanoparticles (GNPs), and the capture antibody was labeled with biotin. The presence of targeting antigen HBeAg in blood sample would act as a bridge with biotinylated captured antibody and GNP-conjugated detection antibody to form the dendritic nanoparticle complex. The dendritic complexes in the sample solution were migrated and immobilized on the testing line of strip coated with antibiotin antibodies. Signal intensity was massively amplified by the SAS, which was positively correlated with the concentration of targeting antigen in the blood sample and was assessed by eyes or strip scanner. The SAS worked only when targeting antigens were present in the sample. By using this SAS-LFIA, we were able to detect a very low concentration of HBeAg (9 ng/mL), which was 27-fold sensitive than that by conventional LFIA (cLFIA). A number of 420 blood samples were detested by this novel SAS-LFIA, the results were in accordance with those of enzyme-linked immunosorbent assay (ELISA) completely, while the cLFIA missed an HBeAg-positive sample. In conclusion, the novel SAS has high specificity and sensitivity, which can be used to replace the conventional rapid test and ELISA in clinical diagnosis.

Glutamate metabotropic receptor 4 (GRM4) inhibits cell proliferation, migration and invasion in breast cancer and is regulated by miR-328-3p and miR-370-3p.

BACKGROUND: Glutamate metabotropic receptors (GRM) play a variety of roles in neuronal cells. However, their clinical significance and biological functions in breast cancer remain unknown. METHODS: RNA sequencing data of breast cancer was obtained from the TCGA dataset (v2) and mined for the expression profiles of GRM family according to cancer subtypes. mRNA expression of GRM family in breast cancer tissues and para-cancerous tissue samples as well as breast cancer cell lines were measured by qPCR. The effects of over- and under-expression of GRM4 on cell capabilities to survive, migrate and invade were determined by colony formation, transwell migration and invasion assays. To explore the upstream regulation pattern of GRM4, miRNAs that target GRM4 were predicted and validated by dual luciferase reporter assay. In addition, the mRNA and protein expression of GRM4 regulated by these miRNAs were further measured by qPCR and western blot assay. RESULTS: GRM4 was the only GRM member that expressed in breast cancer tissues. Ectopic expression of GRM4 was correlated with better prognosis of breast cancer patients. Overexpression of GRM4 could significantly inhibit cell proliferation, migration and invasion capacity in MDA-MB-231, while knockdown of GRM4 could promote these processes. miR-328-3p and miR-370-3p were predicted to regulate the expression of GRM4 and dual luciferase reporter assay demonstrated that miR-328-3p and miR-370-3p directly bound to the 3' UTR of GRM4 and mutations on the binding regions on GRM4 significantly decreased the luciferase activity. qPCR demonstrated that expression of miR-328-3p and miR-370-3p was significantly decreased in breast cancer tissues and cells compared with that in control samples. However, there were no correlations between the expression of miR-328-3p and GRM4, as well as the expression of miR-370-3p and GRM4. Moreover, overexpression of miR-328-3p and miR-370-3p counteracted the inhibitory effect of GRM4-induced cell proliferation, migration and invasion. CONCLUSIONS: Our results suggest that GRM4 might be a tumor suppressor gene in breast cancer under the direct regulation of miR-328-3p and miR-370-3p.

In vitro selection of aptamer S1 against MCF-7 human breast cancer cells.

Breast cancer is the most common female cancer. However, the known effective specific biomarkers for breast cancer are still scarce. Abnormal membrane proteins serve as ideal biomarkers for disease diagnoses, therapeutics and prognosis. Thus aptamers (single-stranded oligonucleotide molecules) with molecular recognition properties can be used as efficient tools to sort cells based on differences in cell surface architecture between normal and tumor cells. In this study, we aimed to screen specific aptamer against MCF-7 human breast cancer cells. Cell-SELEX process was performed to isolate aptamers from a combinatorial single-stranded nucleic acid library that selectively targeting surface proteins of MCF-7 cells in contrast with MCF-10A human mammary epithelial cells. The process was repeated until the pool was enriched for sequences that specifically recognizing MCF-7 cells in monitoring by flow cytometry. Subsequently, the enriched pool was cloned into bacteria, and positive clones were sequenced to obtain individual sequences. Representative sequences were chemically synthesized and evaluated their binding affinities to MCF-7 cells. As a result, an aptamer S1 was finally identified to have high binding affinity with equilibrium dissociation constant (Kd) value of 29.9 ±â€¯6.0 nM. FAM-labeled aptamer S1 induced fluorescence shift in MCF-7 cells but not in MCF-10A human mammary epithelial cells, or MDA-MB-453 and MDA-MB-231 human breast cancer cells. Furthermore, result of cell imaging observed from laser confocal fluorescence microscope showed that MCF-7 cells exhibited stronger fluorescence signal resulted from Cy5-labeled aptamer S1 than MCF-10A cells. The above findings suggested that S1 may be a specificity and selectivity aptamer for MCF-7 cells and useful for the breast cancer detection and diagnosis.

Identification of key genes relevant to the prognosis of ER-positive and ER-negative breast cancer based on a prognostic prediction system.

Few prognostic indicators with differential expression have been reported among the differing ER statuses. We aimed to screen important breast cancer prognostic genes related to ER status and to construct an efficient prognostic prediction system. mRNA expression profiles were downloaded from TCGA and GSE70947 dataset. Two hundred seventy-one overlapping differentially expressed genes (DEGs) between the ER- and ER+ breast cancer samples were identified. Among the 271 DEGs, 109 prognostically relevant mRNAs were screened. mRNAs such as RASEF, ITM2C, CPEB2, ESR1, ANXA9, and VASN correlated strongly with breast cancer prognosis. Three modules, which contained 28, 9 and 8 enriched DEGs, were obtained from the network, and the DEGs in these modules were enriched in response to hormone stimulus, epithelial cell development, and host cell entry. Using bayes discriminant analysis, 48 signature genes were screened. We constructed a prognostic prediction system using the 48 signature genes and validated this system as relatively accurate and reliable. The DEGs might be closely associated with the prognosis in patients with breast cancer. We validated the effectiveness of our prognostic prediction system by GEO database. Therefore, this system might be a useful tool for preliminary screening and validation of potential prognosis indicators for ER+ breast cancer derived from mechanistic research.

[Synthesis and anti-tumor activity of ginsenoside Rh_2 caprylic acid monoester].

Ginsenoside Rh_2,firstly isolated from red ginseng,is protopanaxadiol type of steroidal saponin. Rh_2 possessed variety of activities,but bioavailability of oral administration Rh_2 was extremely low due to poor absorption. Moreover,ginsenoside Rh_2 exhibited toxicity on human normal cells. Therefore,to improve stronger anti-tumor activity and attenuate toxicity,it was essential to design and optimize chemical structure of ginsenoside Rh_2. Through n-octanoylchloride modifications,a novel ester derivative of ginsenoside Rh_2 named caprylic acid monoester of Rh_2( C-Rh_2) was designed and synthesized. Structure of novel ginsenoside derivative was identified by1 D and 2 D NMR,as well as ESI-MS analyses. Anti-tumor effect of C-Rh_2 was tested on H22 tumor bearing mice. C-Rh_2 displayed certain anti-tumor activities and exhibited less toxicity than Rh_2. In the present study,C-Rh_2 as ester form of ginsenoside Rh_2 showed better anti-tumor activity and less toxicity,but the specific mechanism needs further investigation.

Identification of methylation sites and signature genes with prognostic value for luminal breast cancer.

BACKGROUND: Robust and precise molecular prognostic predictors for luminal breast cancer are required. This study aimed to identify key methylation sites in luminal breast cancer, as well as precise molecular tools for predicting prognosis. METHODS: We compared methylation levels of normal and luminal breast cancer samples from The Cancer Genome Atlas dataset. The relationships among differentially methylated sites, corresponding mRNA expression levels and prognosis were further analysed. Differentially expressed genes in normal and cancerous samples were analysed, followed by the identification of prognostic signature genes. Samples were divided into low- and high-risk groups based on the signature genes. Prognoses of low- and high-risk groups were compared. The Gene Expression Omnibus dataset were used to validate signature genes for prognosis prediction. Prognosis of low- and high-risk groups in Luminal A and Luminal B samples from the TCGA and the Metabric cohort dataset were analyzed. We also analysed the correlation between clinical features of low- and high- risk groups as well as their differences in gene expression. RESULTS: Fourteen methylation sites were considered to be related to luminal breast cancer prognosis because their methylation levels, mRNA expression and prognoses were closely related to each other. The methylation level of SOSTDC1 was used to divide samples into hypo- and hyper-methylation groups. We also identified an mRNA signature, comprising eight transcripts, ESCO2, PACSIN1, CDCA2, PIGR, PTN, RGMA, KLK4 and CENPA, which was used to divide samples into low- and high-risk groups. The low-risk group showed significantly better prognosis than the high-risk group. A correlation analysis revealed that the risk score was an independent prognostic factor. Low- and high- risk groups significantly correlated with the survival ratio in Luminal A samples, but not in Luminal B samples on the basis of the TCGA and the Metabric cohort dataset. Further functional annotation demonstrated that the differentially expressed genes were mainly involved in cell cycle and cancer progression. CONCLUSIONS: We identified several key methylation sites and an mRNA signature for predicting luminal breast cancer prognosis. The signature exhibited effective and precise prediction of prognosis and may serve as a prognostic and diagnostic marker for luminal breast cancer.

Association of killer cell immunoglobulin-like receptors with spontaneous clearance of hepatitis C virus in the Chinese population.

BACKGROUND: Natural killer (NK) cells are critical components in innate immune response to viral infection. Killer cell immunoglobulin-like receptors (KIRs) are involved in regulating the balance of activation or inhibitory function of NK cells. However, the association of KIRs with the spontaneous clearance of hepatitis C virus (HCV) remains unclear in the Chinese population. STUDY DESIGN AND METHODS: A total of 407 HCV-seropositive voluntary blood donors were recruited, including 203 with spontaneous viral clearance and 204 with chronic infection. The presence of KIR genes was detected individually by polymerase chain reaction with sequence-specific primers. Data of HLA and interleukin-28B (IL28B) genotypes were extracted from our previous study. RESULTS: Our results showed that KIR2DL2, 2DS2, 2DL2/2DL3, and 2DL5A-/2DL5B+ were more frequent in subjects with HCV clearance than those with chronic infection (odds ratio [OR], 1.640, p = 0.034; OR, 1.664, p = 0.032; OR, 1.636, p = 0.040; and OR, 2.601, p = 0.012, respectively). Multivariate logistic regression analysis showed that KIR2DL5A-/2DL5B+ associated with HCV clearance (OR, 2.448, p = 0.027), independent of sex, IL28B, and other KIRs. In contrast, KIR2DL3/2DL3 (OR, 0.610, p = 0.034) as well as 2DL3/2DL3+HLA-C1 or C1C1 (OR, 0.580, p = 0.017; and OR, 0.639, p = 0.025, respectively) was found associated with chronic HCV infection. The presence of the homozygous KIR2DL3 with or without its HLA ligand increased the OR of developing chronic HCV infection in the context of IL28B. CONCLUSIONS: In this study we identified KIR2DL5A-/2DL5B+ associated with HCV spontaneous clearance, while KIR2DL3/2DL3, 2DL3/2DL3+HLA-C1, or C1C1 associated with chronic infection. Our study highlighted the fact that the roles of KIR and KIR-HLA contributed to the control of HCV infection by innate immune responses.

An evaluation of asymptomatic Dengue infections among blood donors during the 2014 Dengue outbreak in Guangzhou, China.

In 2014, an outbreak of dengue virus (DENV) infection led to 45 171 clinical cases diagnosed in Guangdong province, Southern China. However, the potential risk of blood donors asymptomatically infected with DENV has not been evaluated . In the current study we detected anti-DENV IgG antibody and RNA in volunteer Chinese blood donors. We found that anti-DENV IgG antibody was positively detected in 3.4% (51/1500) and two donors were detected as being DENV RNA positive out of 3000 blood samples. We concluded that the presence of potential DENV in blood donors might be potential risk for blood safety. Therefore, screening for DENV infection should be considered in blood donations during a period of dengue outbreak in high epidemic area of China.