[A review on the prevention and treatment of congenital cytomegalovirus infection in mothers and infants].

Human cytomegalovirus (HCMV) has a high infection rate worldwide, and 85%-90% of congenital cytomegalovirus (CMV) infections are asymptomatic at birth, with the clinical manifestations of hearing loss, psychomotor retardation, and learning disabilities, while 10%-15% are symptomatic infections. Some preterm infants develop CMV infection after birth, which can cause sepsis-like syndrome, thrombocytopenia, neutropenia, liver injury, and lung injury. However at present, women of childbearing age have a lack of awareness of CMV.

The progestin norethindrone affects sex differentiation and alters transcriptional profiles of genes along the hypothalamic-pituitary-gonadal and hypothalamic-pituitary-adrenal axes in juvenile zebrafish Dario renio.

Natural and synthetic progestins may pose a threat to wild fish populations living in receiving waters. In this study, the effects of norethindrone (NET) on the sex differentiation of zebrafish (Dario renio) and the mechanisms underlying these effects were investigated. Juvenile zebrafish (20 days post fertilization, pdf) were exposed to environmentally relevant concentrations (5, 50, 500, and 1000 ng L) for 45 d.

Alterations of secondary sex characteristics, reproductive histology and behaviors by norgestrel in the western mosquitofish (Gambusia affinis).

Synthetic hormones in wastewater effluents released into the aquatic environments may interfere with the normal endocrine systems of fish in receiving streams. Norgestrel (NGT) is a synthetic progestin widely used in oral contraceptives and frequently detected in wastewater effluents. In this study, adult female mosquitofish (Gambusia affinis) were exposed to three environmentally relevant concentrations of norgestrel (NGT) (i.

Aminopeptidase N inhibitor 4cc synergizes antitumor effects of 5-fluorouracil on human liver cancer cells through ROS-dependent CD13 inhibition.

Aminopeptidase N (APN, also known as CD13) is involved in cellular processes of various types of tumors and a potential anti-cancer therapeutic target. Here, we report the effect of an APN inhibitor 4cc in enhancing sensitivity of hepatocellular carcinoma (HCC) cell lines and xenograft model in response to 5-fluorouracil (5-FU) in vivo and in vitro. The treatment of the combination of 4cc with 5-FU, compared to the combination of bestain with 5-FU, markedly suppressed cell growth and induced apoptosis of HCC cells, accompanying the increase in the level of reactive oxygen species (ROS) and followed by a decrease in the mitochondrial membrane potential (ΔΨM).

13F-1, a novel 5-fluorouracil prodrug containing an Asn-Gly-Arg (NO2) COOCH3 tripeptide, inhibits human colonic carcinoma growth by targeting Aminopeptidase N (APN/CD13).

13F-1 is a 5-fluorouracil prodrug containing an Asn-Gly-Arg (NO2) COOCH3 tripeptide. 13F-1 might possess the activity against cancer growth by targeting Aminopeptidase N (APN/CD13). Our goal in this study was to evaluate the inhibitory effect of 13F-1 on the growth of human colonic carcinoma by both in vitro and in vivo studies.

[Effect of Qiling Decoction combined HAART on expression levels of Treg cells and Th17 in HIV/AIDS patients].

Objective: To explore the effect of Qiling Decoction (QD) combined highly active antiretroviral treatment (HAART) on expression levels of peripheral blood Th17 and Treg cells in HIV/AIDS patients.

Methods: Totally 55 HIV/AIDS patients were randomly assigned to the treatment group (28 cases) and the combination group (27 cases). Besides, 21 HIV negative patients were recruited as the healthy control group.

[Advances in the study of structural modifications of multi-target anticancer drug sorafenib].

Sorafenib, the first oral multikinase inhibitor, can inhibit several kinases involved in tumor proliferation and angiogenesis including Raf, VEGFR, PDGFR, kit and so on. Due to the advantages of multi-mechanisms, broad-spectrum anticancer potency, and well-tolerated results in combination trials, more and more researchers have focused on the optimization of sorafenib in order to develop novel multi-targeted anticancer drugs. The present paper reviews the development of modification of sorafenib in recent years from two aspects: bio-isosterism and scaffold hopping.

Effects of PTEN inhibition on regulation of tau phosphorylation in an okadaic acid-induced neurodegeneration model.

One of pathological hallmarks of Alzheimer's disease (AD) is neurofibrillary tangles (NFTs) consisting of abnormally hyperphosphorylated tau. The molecular mechanisms underlying the regulation of tau hyperphosphorylation remain largely unclear. The phosphoinositide 3-kinase (PI3K)/Akt pathway has been implicated in the pathogenesis of AD, however, potential functions and role of tumor suppressor phosphatase and tensin homologue deleted on chromosome 10 (PTEN) in AD pathogenesis have not been fully explored.

[Significance of serum golgi protein 73 (GP73), alpha-fetoprotein (AFP) and lectin-reactive alpha-fetoprotein (AFP-L3) expresssion in primary hepatic carcinoma].

Objective: To explore the alone and joint diagnostic value of serum golgi protein 73 (GP73), alpha-fetoprotein (AFP) and the percentage of lectin-reactive aipha-fetoprotein (AFP-L3) of primary hepatic carcinoma (PHC), and provide a novel method for diagnosis for PHC and screening for high-risk population.

Methods: ELISA was used to detect the serum level of GP73, AFP and AFP-L3% in 81 cases of PHC,176 cases chronic hepatitis and liver cirrhosis, 30 cases other tumber cancer and 40 cases of health people.

Results: The sensitivity of GP73, AFP and AFP-L3% in PHC is 77.

A112, a tamibarotene dimethylaminoethyl ester, may inhibit human leukemia cell growth more potently than tamibarotene.

A112 is a tamibarotene dimethylaminoethyl ester considered a candidate compound for the treatment of acute promyelocytic leukemia (APL) and acute myeloid leukemia (AML). Our goal in this study was to evaluate the efficacy of anti-cancer activity, beginning by studying its inhibitory effects on leukemia cells and then comparing it to tamibarotene. A112 effectively inhibited the growth of HL-60 and NB4 cells as estimated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay.

LYP, a bestatin dimethylaminoethyl ester, inhibited cancer angiogenesis both in vitro and in vivo.

Our previous study revealed that LYP, a bestatin dimethylaminoethyl ester, inhibited the growth of human ovarian carcinoma ES-2 xenografts in mice and suppressed aminopeptidase N (APN/CD13) activity more potently than bestatin. In this study, we examined the inhibitory effect of LYP on migration and formation of capillary tube of human umbilical vascular endothelial cells (HUVECs) in vitro and anti-angiogenesis in ES-2 xenografts in mice. LYP did not possess cytotoxicity to HUVEC proliferation according to the MTT assay and trypan blue exclusion assay.

[Clinical value of CD64 expression in adults with measles complicating bacterial pneumonia].

Objective: To study the clinical value of expression of peripheral blood neutrophil CD64 in adults with measles complicating pneumonia.

Methods: 106 patients were divided into two groups by clinical manifestation and bacteria study: measles complicating bacterial pneumonia group and measles complicating viral pneumonia, using flow cytometry determination of CD64, C-reactive protein (CRP) and white blood cell (WBC) count.

Results: The expression of CD64 in the bacterial pneumonia group with eruptive stage was (32.

N1-acetyl substituted pyrrolidine derivative CIP-A5: a novel compound that could ameliorate liver cirrhosis through modulation of hepatic stellate cell activity.

(2S,4R)-methyl 1-acetyl-4-(N-(4-bromophenyl)sulfamoyloxy)pyrrolidine-2-carboxylate (CIP-A5) is the N1-acetyl substituted pyrrolidine derivative which was designed against the structure of matrix metalloproteinase (MMP-2) and MMP-9. CIP-A5 has been considered as a candidate compound for treatment of liver cirrhosis. In this study, we evaluated the efficacy of CIP-A5 on the activity of hepatic stellate cells.

The Analgesic Activity of Bestatin as a Potent APN Inhibitor.

Bestatin, a small molecular weight dipeptide, is a potent inhibitor of various aminopeptidases as well as LTA4 hydrolase. Various physiological functions of Bestatin have been identified, viz.: (1) an immunomodifier for enhancing the proliferation of normal human bone marrow granulocyte-macrophage progenitor cells to form CFU-GM colonies; Bestatin exerts a direct stimulating effect on lymphocytes via its fixation on the cell surface and an indirect effect on monocytes via aminopeptidase B inhibition of tuftsin catabolism; (2) an immunorestorator and curative or preventive agent for spontaneous tumor; Bestatin alone or its combination with chemicals can prolongate the disease-free interval and survival period in adult acute or chronic leukemia, therefore, it was primarily marketed in 1987 in Japan as an anticancer drug and servers as the only marketed inhibitor of Aminopeptidase N (APN/CD13) to cure leukemia to date; (3) a pan-hematopoietic stimulator and restorator; Bestatin promotes granulocytopoiesis and thrombocytopoiesis in vitro and restores them in myelo-hypoplastic men; (4) an inhibitor of several natural opioid peptides.

LYP, a novel bestatin derivative, inhibits cell growth and suppresses APN/CD13 activity in human ovarian carcinoma cells more potently than bestatin.

LYP is a bestatin dimethylaminoethyl ester which inhibits aminopeptidase N (APN/CD13). Our goal in this study was to evaluate LYP as a candidate compound for cancer treatment, beginning by studying its inhibitory effects on tumors and then comparing it to bestatin. Experiments were performed on human ovarian carcinoma (OVCA) ES-2 and SKOV-3 cell lines, which have high and low levels of APN/CD13 respectively.

Carbohydrate biomarkers for future disease detection and treatment.

Carbohydrates are considered as one of the most important classes of biomarkers for cell types, disease states, protein functions, and developmental states. Carbohydrate "binders" that can specifically recognize a carbohydrate biomarker can be used for developing novel types of site specific delivery methods and imaging agents. In this review, we present selected examples of important carbohydrate biomarkers and how they can be targeted for the development of therapeutic and diagnostic agents.

Targeting aminopeptidase N (APN/CD13) with cyclic-imide peptidomimetics derivative CIP-13F inhibits the growth of human ovarian carcinoma cells.

Aminopeptidase N (APN/CD13) is an essential peptidase involved in the process of tumor growth, metastasis and angiogenesis. Inhibition of APN/CD13 may be an effective strategy for cancer treatment. CIP-13F is a cyclic-imide peptidomimetics compound designed to fit the active pockets S1 and S'1 of APN/CD13 that act in tumor proliferation.

Pharmacophore model of influenza neuraminidase inhibitors--a systematic review.

Recently, the worldwide spread of A/H5N1 avian influenza with high virulence has highlighted the potential threat of a human influenza pandemic. The viral surface glycoprotein, neuraminidase (NA), has been found to be a potential target to control influenza virus. With an understanding of the enzyme mechanism, the X-ray crystallographic structures of NA and its substrate or inhibitors, and progress in computational chemistry, the information about NA binding sites and pharmacophore models is derived from existing inhibitors and will serve as design guidelines of more potent agents against NA.

Ligustrazine derivatives. Part 3: Design, synthesis and evaluation of novel acylpiperazinyl derivatives as potential cerebrocardiac vascular agents.

A series of novel acylpiperazinyl Ligustrazine derivatives was designed, synthesized, and their protective effects on damaged ECV-304 cells and antiplatelet aggregation activities were evaluated. The results showed that compound E33 displayed most potential protective effects on the ECV-304 cells damaged by hydrogen peroxide, and compound E1 was found to be the most active antiplatelet aggregation agent. Structure-activity relationships were briefly discussed.

5-(Methoxy-carbon-yl)thio-phene-2-carboxylic acid.

In the title compound, C(7)H(6)O(4)S, a monoester derivative of 2,5-thio-phene-dicarboxylic acid, the carboxylic acid and the carboxylic acid ester groups are approximately coplanar with thio-phene ring, making a dihedral angle of 3.1 (4) and 3.6 (4)°, respectively.

Galloyl cyclic-imide derivative CH1104I inhibits tumor invasion through suppressing matrix metalloproteinase activity.

Matrix metalloproteinase (MMP)-2 and MMP-9 have been associated with the ability of tumor cells to metastasize because of their capacity to degrade type IV collagen, the main component of basement membrane, and to their elevated expression in malignant tumors. (S)-methyl 6-(benzyloxycarbonylamino)-2-(2-((S)-2,6-dioxo-3-(3,4,5-trimethoxybenzamido) piperidin-1-yl) acetamido) hexanoate (CH1104I) is a galloyl cyclic-imide derivative designed to fit and extend into the S1' active pocket of MMP-2 and MMP-9. We aimed to evaluate the efficacy of CH1104I as a candidate compound for antiinvasion and antimetastasis of tumor cells.

Synthesis of new sulfonyl pyrrolidine derivatives as matrix metalloproteinase inhibitors.

A series of new sulfonyl pyrrolidine derivatives was designed, synthesized, and assayed for their inhibitory activities on matrix metalloproteinase 2 (MMP-2) and aminopeptidase N (AP-N). The results showed that these pyrrolidine derivatives exhibited highly selective inhibition against MMP-2 as compared with AP-N. The compounds 4c, 4j, 5a, and 5b were equally or more potent MMP-2 inhibitors than the positive control LY52.

Novel aminopeptidase N inhibitors derived from 1,3,4-thiadiazole scaffold.

The aminopeptidase N (APN/CD13), overexpressed in tumor cells, plays a critical role in angiogenesis. In this study, we report the synthesis and in vitro enzyme inhibition assay of 1,3,4-thiadiazole scaffold compounds. These new compounds have potent inhibitory activities toward APN with IC(50) values in the micromol rang.

Progress in the development of matrix metalloproteinase inhibitors.

Matrix metalloproteinases (MMPs) are a family of zinc-dependent proteinases involved in the degradation and remodeling of extracellular matrix proteins that are associated with the tumorigenic process. MMPs promote tumor invasion and metastasis, regulating host defense mechanisms and normal cell function.Thus, MMP inhibitors (MMPIs) are expected to be useful for the treatment of diseases such as cancer, osteoarthritis, and rheumatoid arthritis.

Design, synthesis and evaluation of novel sulfonyl pyrrolidine derivatives as matrix metalloproteinase inhibitors.

A series of novel sulfonyl pyrrolidine derivatives were designed, synthesized and assayed for their inhibitory activities on matrix metalloproteinase 2 (MMP-2) and aminopeptidase N (AP-N). The results showed that these pyrrolidine derivatives exhibited highly selective inhibition against MMP-2 as compared with AP-N. Compounds 6a-d were more potent MMP-2 inhibitors than the positive control LY52.